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How the nervous and immune systems communicate, using peptides and other signals, to regulate pain, itch, and inflammation.

TOPICS DISCUSSED:

• Nociception & Pathogens: Sensory neurons detect bacterial toxins within seconds, enabling rapid host-defense coordination ahead of immune-cell recruitment.
• CGRP & neutrophils: Nociceptor-release the peptide CGRP, which blocks neutrophil (immune cell) recruitment; pathogens exploit this in necrotizing fasciitis and meningitis.
• Pain sensitization: Inflammation can lower neuronal thresholds for pain, which sometimes becomes a chronic problem.
• Gut barrier protection: CGRP from gut nociceptors drives goblet-cell mucus secretion, supporting the protective “weep and sweep” response.
• Skin-to-gut allergy priming: Early skin exposure to allergens plus scratching may promote food allergies.
• Vagus nerve circuits: Distinct vagal sensory neurons selectively suppress TNF or induce IL-10, allowing precise inflammatory control.
• Brain inflammatory memory: Insular neurons encode site-specific immune responses that can later be recalled by reactivating those circuits. The brain remembers past inflammatory events.

ABOUT THE GUEST: Isaac Chiu, PhD is a professor in the Department of Immunology at Harvard Medical School. His lab studies nervous-immune system crosstalk in pain, itch, infection, and inflammatory disease.

RELATED CONTENT:

Article | Inflammation Regulation by Omega Fats: How High ω-6 Intake Impacts ω-3 Levels

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Mitochondrial peptide MOTS-c is a stress-induced signal that reprograms cell metabolism.

TOPICS DISCUSSED:

• Mitochondrial Roles: Not just ATP production, but “speaker of the house” via communication molecules that “talk” to the rest of the cell.
• Origin of Communication: Mitochondrial peptides were likely co-opted from ancient antimicrobial factors to synchronize nuclear and mitochondrial genomes.
• MOTC Discovery: Identified in mitochondrial ribosomal RNA regions linked to interferon responses.
• Stress Induction: MOTS-c is produced in response to exercise, immune activation, and nutrient withdrawal; circulates as a mitokine.
• Nuclear Regulation: MOTS-c translocates to the nucleus under stress and acts as a nonspecific cofactor that shapes chromatin accessibility and gene expression.
• Metabolic Effects: Prevents diet-induced obesity and fatty liver in mice without altering baseline weight; engages AMPK and suppresses anabolic pathways.
• Immune Modulation: Shifts immune cell programs to reduce autoimmune attack in type 1 diabetes models.
• Aging Phenotypes: Daily or intermittent dosing doubles running capacity and preserves walking ability in old mice.

ABOUT THE GUEST: Changhan David Lee, PhD is Associate Professor at the University of Southern California Leonard Davis School of Gerontology. His laboratory investigates mitochondrial communication and microproteins in the biology of aging.

RELATED CONTENT:

• Article | MOTS-c & Cellular Energy Homeostasis

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GHK-Copper and peptides in skin care, aging, and general health.

TOPICS DISCUSSED:

• Endogenous Decline: GHK-copper levels peak in young adulthood then fall with age, reducing natural support for skin repair and collagen maintenance.
• Skin Penetration: Effective topical delivery depends on molecular size under and fat solubility, often improved by procedures such as microneedling that briefly disrupt the barrier.
• Mechanisms of Action: The peptide upregulates fibroblasts and vascular endothelial growth factor, stimulates glycosaminoglycan production, and alters expression of genes involved in tissue regeneration and oxidative stress reduction.
• Lasting Remodeling: Gene expression changes produce sustained collagen rebuilding that develops over weeks to months rather than delivering only transient effects.
• Administration Routes: Topical use is accessible and pairs well with hyaluronic acid for hydration; injectables may reach higher local concentrations but lack extensive human trial data and FDA approval for this purpose.
• Safety & Protocols: The compound is generally well tolerated with mild transient injection-site reactions; typical approaches use daily microgram doses for one to two months followed by off periods.
• Hair & Other Uses: Clinical observations indicate potential for hair shaft strengthening comparable to minoxidil with a favorable side-effect profile, alongside exploratory work in wound healing and neurological contexts.
• Research Needs: Expanded human studies are required to standardize dosing, confirm long-term safety, and evaluate value in neurodegeneration, lung repair, and related areas.

ABOUT THE GUEST: Rahi Sarbaziha, MD is a physician in Beverly Hills, California whose practice focuses on regenerative aesthetics, hormone therapies, peptides, and interventions that support vitality, tissue repair, and overall wellness.

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Blood-brain barrier as a dynamic interface allowing selective passage of nutrients, peptides, and gut hormones.

TOPICS DISCUSSED:

• Blood-Brain Barrier Structure: Capillary endothelial cells with tight junctions, absent fenestrae, and minimal vesicles create a selective interface; supported by astrocytes and pericytes.
• Crossing Mechanisms: Lipid-soluble small molecules diffuse passively; glucose, amino acids, and regulatory peptides use saturable transporters whose rates vary by need.
• Peptide Transport: Many peptides cross via lipid solubility or specific transporters; rate, not all-or-none presence, determines biological relevance; efflux systems remove some (e.g. certain enkephalins).
• Dynamic Regulation: Transporters for leptin and insulin are modulated by epinephrine, triglycerides, and brain demand; changes occur in aging and Alzheimer’s (reduced glucose uptake, impaired Aβ efflux).
• Circumventricular Organs: Leaky capillary regions allow rapid sampling of blood signals while tanycytes limit spread to surrounding brain tissue.
• Drug Delivery Challenges: Small lipid-soluble drugs, barrier disruption (e.g. focused ultrasound), and “Trojan-horse” strategies each have limitations; intranasal delivery shows rapid brain distribution.
• Peptides & Brain Effects: Gut peptides like GLP-1 analogs, insulin, and ghrelin influence cognition and memory; brain entry predicts central effects.

GUEST: William Banks, MD is a physician-scientist and leading researcher on the blood-brain barrier. He has focused on humoral brain-body communication, peptide transport, and the barrier’s role in health and disease.

RELATED CONTENT:

• M&M 298 | GLP-1s & Novel Peptides in Obesity, Diabetes & Metabolic Health | Katrin Svensson

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Ferroptosis, an iron-dependent cell death pathway driven by lipid peroxidation; chronoferoptosis, in which chronic stress sensitizes neurons gradually.

TOPICS DISCUSSED:

• Cell Death Pathways: Apoptosis proceeds through regulated steps with surface “eat me” signals that enable non-inflammatory clearance by phagocytes, whereas ferroptosis and related pathways release cellular contents that can amplify local damage and inflammation.
• Ferroptosis Discovery: Work on glutamate toxicity in neuronal cell lines first identified a glutathione-depletion pathway termed oxytosis; parallel studies in cancer cells renamed and generalized it as ferroptosis to highlight iron’s catalytic role.
• Lipid Peroxidation: Polyunsaturated fatty acids in membranes are oxidized non-enzymatically when ferrous iron reacts with hydrogen peroxide in the Fenton reaction, generating hydroxyl radicals that produce toxic lipid peroxides and reactive carbonyls that modify proteins.
• GPX4 & Glutathione: Glutathione peroxidase-4 is an enzyme that reduces lipid peroxides within membranes and requires glutathione as cofactor; depletion of either component removes this critical line of defense.
• Chronoferoptosis: Nine-day treatment of differentiated neuronal cells with chronic iron or glutathione synthesis inhibitor reduced GPX4 protein, raised basal lipid peroxidation, and increased cell death after addition of otherwise sublethal secondary stressors.
• Protective Compounds: Screening identified flavonoids such as fisetin and sterubin plus synthetic molecules J-147 and CMS-121 that block lipid peroxidation directly or indirectly and, in several cases, also raise glutathione levels.
• Human Disease Evidence: Postmortem brain tissue from Alzheimer’s and Parkinson’s patients shows elevated lipid peroxidation markers and altered iron handling in vulnerable regions; similar changes appear in animal models of multiple diseases.
• Dietary & NRF2 Links: Compounds that activate the NRF2 transcription factor, including sulforaphane from broccoli and certain flavonoids, upregulate antioxidant enzymes including GPX4 and may support long-term cellular resilience.

ABOUT THE GUEST: Pamela Maher, PhD is a research professor at the Salk Institute for Biological Studies in La Jolla, California. Her laboratory studies ferroptosis mechanisms in neurodegenerative diseases and works to identify compounds that inhibit iron-dependent lipid peroxidation.

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Endogenous peptide diversity, GLP-1 drugs, and methods for novel peptide discovery.

TOPICS DISCUSSED:

• Peptide Structure & Production: Short amino acid chains (3-50 residues) cleaved from larger precursors by PCSK enzymes, stored in dense-core vesicles, and released upon stimuli rather than acting as folded enzymes like proteins.
• Tissue-Specific Processing: The same precursor yields different peptides by tissue; preproglucagon produces glucagon in pancreas but GLP-1 in gut L-cells due to distinct cleavage patterns.
• Signaling Timescales: Peptides act over minutes via GPCRs and can drive longer transcriptional changes such as FOS expression, yet are cleared rapidly by proteases and kidneys.
• Endogenous GLP-1: Meal-stimulated incretin from gut that boosts insulin secretion with a half-life of only minutes, limiting primary action to periphery rather than deep brain structures.
• GLP-1 Engineering for Brain Access: DPP4 site mutations plus lipid conjugation enable albumin binding, extend half-life, and raise brain exposure.
• Dose-Dependent Effects: Low GLP-1 doses mainly lower blood glucose via pancreas; higher doses engage hindbrain and hypothalamic neurons to suppress appetite and alter food preference.
• Novel Peptide Discovery: Computational scans across the genome flag hundreds of uncharacterized precursors, facilitating new peptide discovery.
• BRP Peptide: This newly discovered brain-derived peptide suppresses feeding in GLP-1 receptor knockout mice, activates non-overlapping neurons, and does not slow gastric emptying.

ABOUT THE GUEST: Katrin Svensson, PhD, is a biochemist and physiologist who leads a laboratory at Stanford University focused on peptide hormone physiology and the regulation of energy balance.

PRACTICAL TAKEAWAYS:

• GLP-1 drugs require higher doses to engage brain satiety circuits for meaningful weight loss; lower doses primarily improve glucose control with little effect on appetite.
• Response varies widely across individuals, with some losing over 25% body weight while others see minimal change.
• Emerging peptides under study may suppress appetite via brain pathways that avoid the gastric slowing responsible for common GI side effects of current GLP-1 drugs.
• Research peptides purchased online frequently show variable purity below pharmaceutical standards and may contain unsafe formulation components or aggregates.

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The possible role of deuterium (heavy isotope of hydrogen) in regulating cell division, mitochondrial metabolism & cancer.

TOPICS DISCUSSED:

• Deuterium Basics: Deuterium is twice as massive as regular hydrogen; natural water contains ~150 ppm, with stronger oxygen-deuterium bonds slowing reactions compared to oxygen-hydrogen.
• Mitochondrial Role: Healthy mitochondria produce deuterium-depleted metabolic water (~110 ppm from fat oxidation vs. ~150 ppm from carbs), helping maintain low cellular D:H ratios.
• Cell Growth Regulation: Lower deuterium slows cell division in vitro; cells sense small D:H changes, with higher levels (near/above 150 ppm) promoting growth.
• In Vitro Evidence: DDW (e.g., 25-125 ppm) can reduce proliferation and alters cancer-related gene expression.
• Animal Models: DDW caused tumor regression in mice with transplanted human cancers and showed possible efficacy in veterinary use for dogs and cats.
• Human Prostate Cancer: Phase 2 randomized study showed greater Prostate-Specific Antigen (PSA) reduction, tumor shrinkage, and better 1-year survival with DDW plus standard therapy vs. placebo.
• Dietary Modulation: Ketogenic/high-fat diets lower body deuterium from lipid oxidation.
• Broader Implications: Potential in neurodegeneration models; larger trials needed for registration as adjunct cancer therapy.

ABOUT THE GUEST: Gábor Somlyai, PhD is a molecular biologist who pioneered deuterium depletion studies at the National Institute of Oncology in Hungary. His primary work focuses on the role of deuterium in living organisms and the development of deuterium-depleted water for cancer therapy.

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New research finds that excess antioxidants can support tumor growth in preexisting cancers.

TOPICS DISCUSSED:

• Oxidative Stress: Reactive oxygen species (ROS) generated by mitochondrial metabolism cause damage; context determines whether they promote or suppress cancer.
• Glutathione Biology: Primary cellular antioxidant made from cysteine, glycine, and glutamate; works with peroxidase enzymes to protect against ROS.
• Antioxidant Paradox: Clinical trials (SELECT vitamin E, beta-carotene) showed supplements increased cancer rather than preventing it.
• Cancer Antioxidant Hijacking: Tumors ramp up antioxidant systems to handle high metabolic rates and survive stress including metastasis.
• Extracellular Glutathione Catabolism: Cancer cells break down external glutathione into amino acids, particularly cysteine, to fuel growth (new findings).
• Therapeutic Window: Blocking glutathione breakdown slows tumors in models while sparing normal cells.
• Diet vs Supplements: Balanced diets support glutathione needs; excess isolated antioxidants may enrich the tumor microenvironment.

ABOUT THE GUEST: Isaac Harris, PhD is a biologist working on the role of antioxidants in health, disease, and cancer metabolism.

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Fructose survival hypothesis: how fructose metabolism in the liver triggers ATP depletion, uric acid production, oxidative stress, lipogenesis & leptin resistance.

TOPICS DISCUSSED:

• Glucose vs Fructose Metabolism: Fructose is rapidly metabolized in the liver by fructokinase without feedback, causing ATP depletion and uric acid production, unlike glucose metabolism.
• Liver Effects: Fructose induces uric acid production, NADPH oxidase activation, mitochondrial oxidative stress, and de novo lipogenesis even under caloric restriction.
• Fructose Survival Hypothesis: Fructose signaling promotes fat storage, leptin resistance, foraging behavior, and metabolic syndrome as adaptations for hibernation or starvation, including metabolic water production.
• Brain Impacts: Endogenous fructose production from glucose (polyol pathway) triggered by high glucose, salt, or stress leads to insulin resistance, mitochondrial damage, and neuroinflammation in Alzheimer’s-vulnerable regions.
• Evolutionary Context: Human uricase mutation ~12 million years ago enhanced fructose effects for fat storage during seasonal starvation but increases vulnerability today.
• Modern Triggers: Added sugars, high fructose corn syrup, salt-sugar combinations, and omega-6 fats synergize with fructose to amplify inflammation, appetite, and disease risk.
• Alzheimer’s Link: Fructose-driven brain changes mirror Alzheimer’s pathology, with high brain fructose in patients and potential for fructokinase inhibitors as therapy.

ABOUT THE GUEST: Richard Johnson MD, is a professor of medicine who has conducted clinical practice and NIH-funded research on sugar metabolism since the late 1990s. His work focuses on the role of fructose in metabolic syndrome, obesity, and related diseases.

RELATED CONTENT:

• Article | Dietary Fructose & Metabolic Health: An Evolutionary Perspective
• M&M 249: Fructose, Microglia, Anxiety & Brain Development | Justin Perry | 249

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Deep-dive into a 2026 cardiology review paper claiming seed oils reduce inflammation, exposing misrepresentations of cited clinical trials, and detailing how oxidized Ω-6 fats trigger inflammation.

Companion article: Click HERE

TOPICS DISCUSSED:

• Seed Oil Profiles: Typical seed oils like sunflower are high in linoleic acid (omega-6 PUFA), while canola is higher in monounsaturated fats and resembles olive oil.
• Review Paper Critique: The 2026 JACC review falsely claims sunflower oil reduce inflammation like olive oil, citing an RCT that showed benefits only for canola and olive.
• RCT Analysis: In Iranian women with metabolic issues, switching to canola or olive oil lowered CRP by increasing MUFA and decreasing PUFA intake; sunflower oil produced no change.
• CRP Biology: CRP responds to oxidized lipids and cellular damage patterns, rising with exercise or infection and marking oxidized Ω-6 metabolites in modern diets.
• Oxidized Lipids: Ω-6 fats in LDL and cardiolipin oxidize easily, generating 4-HNE, MDA, and other signals that trigger immune clearance, similar to bacterial threats.
• Sterile Inflammation: High dietary linoleic acid causes chronic immune activation without pathogens, potentially contributing to metabolic and cardiovascular issues.

PRACTICAL TAKEAWAYS:

• Prioritize monounsaturated fats from olive or avocado oil over high-linoleic seed oils like standard sunflower or soybean for lower oxidative stress potential.
• Check labels for high-oleic versions of sunflower oil, which shift the profile toward monounsaturated fats.
• Evaluate nutrition claims by examining original studies and fatty acid compositions rather than accepting review summaries at face value.

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Human genetic variation in dietary fat metabolism and its implications for health & disease.

TOPICS DISCUSSED:

• Linoleic Acid Rise: Linoleic acid now comprises 6-8% or more of energy in Western diets.
• Metabolic Pathways: Omega-6 linoleic acid converts to arachidonic acid and pro-inflammatory oxylipins; omega-3 ALA converts via shared enzymes to EPA/DHA with anti-inflammatory effects.
• FADS Genetic Variants: Ancestry-linked haplotypes in the FADS cluster create large “pipe” size differences, altering fatty acid by up to 40% between ancestral and derived versions.
• Population Differences: African ancestry populations often have high-conversion “big pipe” genotypes; Indigenous American ancestry populations have low-conversion “small pipe” genotypes; European ancestry comes with a mix of both.
• Omega-3 Deficiency: High linoleic intake suppresses EPA production, especially in small-pipe populations, contributing to hypertriglyceridemia and fatty liver in Mexican cohorts.
• Clinical Evidence: Reanalysis of VITAL trial showed 83% reduction in myocardial infarction with omega-3 supplementation in African Americans; Mexican data link low EPA to unique diabetes forms.
• Methodological Issues: Compositional data (from GC-FID measurements) versus absolute concentration measurements can flip relationships between linoleic acid and key biomarkers.

ABOUT THE GUEST: Floyd Chilton PhD is Professor and Director of the Center for Precision Nutrition and Wellness at the University of Arizona. His research focuses on functional genomics, fatty acid metabolism, and precision nutrition, particularly how genetic ancestry influences responses to dietary fats.

RELATED EPISODE:

• M&M 291: Omega Polyunsaturated Fats & Inflammation | Philip Calder

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Pregnenolone, a neurosteroid derived from cholesterol, affects brain activity and shows promise for treating mood and substance abuse disorders.

TOPICS DISCUSSED:

• Steroid Biosynthesis: Cholesterol converted to pregnenolone, the precursor for all steroid hormones including cortisol, aldosterone, and sex hormones.
• Corticosteroids: Synthetic versions like prednisone primarily target glucocorticoid receptors for anti-inflammatory uses but can impact mood and cognition.
• Pregnenolone Mechanisms: Positive allosteric modulator of NMDA receptors for cognition and negative allosteric modulator of CB1 cannabinoid receptors.
• Allopregnanolone: GABAergic derivative of pregnenolone; its IV form Brexanolone is FDA-approved for postpartum depression.
• Clinical Trials: Pregnenolone at 100-500 mg improved depressive symptoms in placebo-controlled studies of bipolar disorder patients.
• Cannabis Interaction: THC robustly induces brain pregnenolone production; supplementation may reduce cannabis and alcohol use.
• Corticosteroid Brain Impact: Prednisone use associated with smaller hippocampal volumes and memory deficits.

ABOUT THE GUEST: Sherwood Brown, MD, PhD is Vice Chair for Clinical Research in the Department of Psychiatry at the University of Texas Southwestern Medical Center in Dallas. With a background in chemistry, his research focuses on steroids and comorbidities in people with mood disorders.

RELATED EPISODE:

• M&M 124: Hormonal Contraception, Sex Hormones, Menstruation, Pregnancy, Puberty, Estrogens, Androgens, Effects of Birth Control on Cognition | Adriene Beltz

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How omega-3 fats in human health, including dietary intake needs, supplements, & omega fat testing.

TOPICS DISCUSSED:

• ω-3 chemistry: EPA and DHA differ from plant ALA in chain length and double-bond count, making them structurally and biologically distinct — and largely irreplaceable by ALA conversion.
• ALA-to-EPA/DHA conversion: A small percentage of dietary ALA converts to EPA, and conversion to DHA is even lower; vegans rely on this inefficient pathway for all long-chain omega-3s.
• Cardiovascular mechanisms: ω-3s lower triglycerides, reduce platelet stickiness, improve endothelial function, and slow resting heart rate, reducing cardiovascular risk.
• ω-3 Index: Defined as red blood cell EPA+DHA as a percent of total fatty acids; 8–12% is the target range, while most Americans sit around 4–5%.
• Brain & dementia risk: Higher DHA blood levels are associated with significantly lower risk of dementia and Alzheimer’s in large cohorts including the UK Biobank and Framingham.
• Linoleic acid nuance: Higher blood levels of dietary linoleic acid (omega-6) associate with lower dementia and cardiovascular risk; downstream omega-6 metabolites — not linoleic acid itself — associate with adverse outcomes.
• Supplementation practicalities: Most people need 1–2 g/day of EPA+DHA to reach an ω-3 Index >8%; oxidation concerns with fish oil supplements may be overstated.

ABOUT THE GUEST: Bill Harris, PhD is founder of both OmegaQuant Laboratory and the Fatty Acid Research Institute (Sioux Falls, SD), where his work centers on blood fatty acid biomarkers as predictors of disease risk in large population cohort studies.

KNOW YOURSELF:

• OmegaQuant: At-home blood testing to see fatty acid profiles, including omega-3 fatty acids. Use link to see options and support M&M.

RELATED EPISODE:

• M&M 134: Omega Fats, Vegetable & Seed Oils, Sugar, Processed Food, Metabolic Health & Dietary Origins of Chronic Inflammatory Disease | Artemis Simopoulos

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How dietary fatty acids regulate the initiation, propagation, and resolution of inflammation.

TOPICS DISCUSSED:

• Parenteral nutrition history: IV nutrition evolved from soybean oil alone in the 1960s to complex blends including fish oil as the biology of ω-3s became understood.
• Three phases of inflammation: Initiation, propagation (driven by ω-6–derived prostaglandins and leukotrienes), and active resolution (driven by ω-3-derived resolvins and protectins).
• Pro-resolving mediators: Resolution is an active biological process, not passive; EPA and DHA generate resolvins and protectins that actively terminate inflammation.
• Aspirin’s ω-3 mechanism: Aspirin inhibits arachidonic acid metabolism but allows EPA/DHA to access COX-2, upregulating pro-resolution mediators — a likely underappreciated mechanism of action.
• Cell membrane competition: EPA and DHA physically displace arachidonic acid in membranes, shifting the balance of mediators produced and improving resolution capacity.
• Linoleic acid & EPA synthesis: High linoleic acid intake saturates shared desaturase enzymes, inhibiting the body’s conversion of ALA to EPA — meaning reducing ω-6 can raise ω-3 levels without supplementation.
• Dose & timing of ω-3 incorporation: ~2g/day of EPA+DHA shifts the arachidonic acid-to-EPA ratio enough to measurably reduce prostaglandin E2 production; white blood cells reflect changes within a month.

ABOUT THE GUEST: Philip Calder, PhD is Professor of Nutritional Immunology in the Faculty of Medicine at the University of Southampton. His research focuses on how dietary fatty acids — particularly omega-3s — modulate immune responses and inflammatory processes across clinical and healthy populations.

RELATED EPISODE:

• M&M 200: Dietary Fats & Seed Oils in Inflammation, Colon Cancer & Chronic Disease | Tim Yeatman & Ganesh Halade

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A metabolic view of Alzheimer's disease & the recent discovery of compounds that reverse advanced disease symptoms in mouse models by restoring mitochondrial health.

TOPICS DISCUSSED:

• Classic Alzheimer’s pathology: amyloid plaques and tau tangles identified over 120 years ago, long assumed to drive irreversible neuron loss.
• Limitations of amyloid focus: plaques appear in some cognitively normal brains; antibody therapies have shown limited clinical benefit.
• Metabolic perspective: brain energy failure as a tipping point where repair mechanisms are overwhelmed, linking genetics, injury, and aging.
• Neuroprotection via P7C3 compounds: discovered through hippocampal neurogenesis screen; preserves mitochondrial function and normalizes NAD/NADH ratio without elevating NAD excessively.
• Recovery in models: treatment after symptom onset reversed cognitive deficits, blood-brain barrier damage, oxidative stress, and axon issues in amyloid and tau mouse models, despite persistent plaques.
• Broader implications: energy restoration enables surviving neurons to function; similar protective effects seen in TBI and other organs under stress.

ABOUT THE GUEST: Andrew Pieper, MD, PhD, is a board-certified psychiatrist and neuroscientist, professor at Case Western Reserve University, and director of the Brain Health Medicines Center at the Harrington Discovery Institute. He directs a research group focused on neuroprotection after brain injury and neurodegenerative disease.

RELATED EPISODE:

• M&M 208: Glyphosate, Choline & Alzheimer’s: Toxins & Nutrition to Prevent Neurodegeneration | Ramon Velazquez

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How exercise in parents can improve the metabolic and cardiovascular health of their offspring through epigenetic mechanisms.

TOPICS DISCUSSED:

• Parental exercise & offspring metabolic health: exercise before and during pregnancy improves glucose tolerance and reduces fat gain in offspring.
• Paternal effects via sperm: moderate voluntary wheel running alters small non-coding RNAs, especially tRNA fragments, in sperm and enhances glucose clearance, with stronger benefits in female offspring.
• Maternal exercise mechanisms: benefits arise from in utero environment, placental changes, and breast milk composition rather than major oocyte alterations.
• Human milk oligosaccharides: exercise increases 3’-sialyllactose in milk, linked to better offspring microbiome and metabolic outcomes.
• Sex-biased & intergenerational effects: maternal exercise impacts male offspring metabolism more; effects can transmit to F2 generation depending on the transmitting parent’s sex.

ABOUT THE GUEST: Kristin Stanford, PhD is an associate professor in the Department of Physiology and Cell Biology at The Ohio State University Wexner Medical Center, where she serves as associate director of the Diabetes and Metabolism Research Center. Her lab investigates molecular mechanisms by which exercise enhances metabolic and cardiovascular health, with a focus on intergenerational effects.

RELATED EPISODE:

• M&M 145: Epigenetics, Endocrine Disruptors, Obesogens & Obesity, Inheritance of Acquired Characteristics | Bruce Blumberg

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How the vagus nerve regulates inflammation; bioelectronic therapies to treat inflammatory conditions.

Nick speaks with Dr. Kevin Tracey about inflammation as a major driver of modern diseases, the vagus nerve’s role in balancing immune responses via reflexes, limitations of anti-cytokine drugs, and emerging bioelectronic medicine using targeted nerve stimulation.

TOPICS DISCUSSED:

• Inflammation is related to diseases that contribute to most deaths today: heart disease, diabetes, neurodegeneration, and cancer.
• Molecular signals involved in inflammation, such as cytokines.
• Homeostasis is maintained by push-pull mechanisms, with excitatory and inhibitory responses co-deployed in ways that maintains balance.
• The vagus nerve’s anatomy, sensory/motor fibers, and the inflammatory reflex that suppresses cytokine production in the spleen via acetylcholine and norepinephrine.
• Vagus nerve stimulation devices delivering brief daily pulses to reduce inflammation without broad immunosuppression, now FDA-approved for refractory rheumatoid arthritis.
• Challenges in measuring inflammation and oversimplifications online about “stimulating” the vagus nerve.

ABOUT THE GUEST: Kevin Tracey, MD is a neurosurgeon, president and CEO of the Feinstein Institutes for Medical Research at Northwell Health, and professor of molecular medicine and neurosurgery. He discovered the inflammatory reflex, showing how the vagus nerve controls immune responses, and co-founded SetPoint Medical to develop FDA-approved vagus nerve stimulation for rheumatoid arthritis.

RELATED EPISODE:

• M&M 143: Gut-Brain Communication, Vagus Nerve, Fats & Sugars, Food Addiction, Gut Hormones & Weight Loss Drugs | Will de Lartigue

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How light regulate circadian rhythms, mitochondrial function, hormones, and appetite.

Nick & Dr. Alexis Cowan discuss non-image-forming effects of light on the body, from melanopsin-driven circadian signaling in the eye to UV-stimulated pathways in skin and brain that influence melatonin, cortisol, melanin production, and energy balance.

TOPICS DISCUSSED:

• Melanopsin & non-image-forming light: blue light signals daytime to the SCN master clock, suppressing melatonin and promoting alertness.
• UV light, POMC & peptide hormones: UVB exposure in skin and hypothalamus produces alpha-MSH (reduces appetite, boosts energy expenditure) and beta-endorphin (improves mood), independent of vitamin D.
• Mitochondrial effects of light: red/infrared supports function like a gas pedal; isolated blue light acts as brakes, impairing energy production and biophoton signaling.
• Artificial light: Evening blue light from screens inhibits melatonin, poisons mitochondria, and creates discordant timing signals versus balanced natural sunlight.
• Melanin beyond skin: produced via UVB, it harnesses energy, buffers oxidative stress, and links to dopamine pathways; low sun exposure ties to metabolic issues and conditions like Parkinson’s.
• Vitamin D as biomarker: supplementation shows limited benefits because it reflects broader UVB-driven processes, not a standalone fix.

ABOUT THE GUEST: Alexis Cowan, PhD earned her PhD in molecular biology at Princeton in the Rabinowitz lab, a leading metabolism research group, where she studied fasting, ketogenic diets, and exercise; she completed a postdoc at UPenn before shifting focus to circadian and quantum biology. She now educates on light, mitochondria, and quantum biology.

RELATED EPISODE:

• M&M 221: Regenerative Energy & the Light Inside You | Jack Kruse

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Is the fundamental purpose of sleep to remove oxidized fats from the brain?

Nick & Dr. Amita Sehgal talk about the latest science on why animals sleep. Using fruit flies, her lab shows that waking generates oxidized lipids in neurons that are shuttled to glia and then cleared by macrophage-like cells during sleep. This process protects mitochondria, supports memory, and links sleep to metabolic cleanup rather than just rest.

TOPICS DISCUSSED:

• Drosophila as a model: Fruit flies sleep with immobility, reduced responsiveness, and homeostatic rebound; their genetics reveal conserved mechanisms found in humans.
• Circadian vs homeostatic sleep: Circadian timing sets when we sleep; homeostatic drive builds need from prolonged wakefulness independent of time of day.
• Metabolic waste during wake: Neuronal activity oxidizes lipids in mitochondria; these damaged lipids transfer to glial support cells via apolipoproteins.
• Immune cells clear brain trash: Macrophage-like hemocytes dock at the brain during sleep, phagocytose oxidized lipids, and remove them; blocking this docking reduces sleep and impairs memory.
• Peroxisomes & oxidative stress: These organelles handle specific fats and rise with wakefulness; disrupting them increases brain oxidation that can be partially rescued by antioxidants like N-acetylcysteine.
• Sickness sleep differs from normal sleep: Infection-induced sleep redirects energy to immune defense and depletes rather than restores brain energy stores.

ABOUT THE GUEST: Amita Sehgal, PhD is the John Herr Musser Professor of Neuroscience at the University of Pennsylvania, an HHMI Investigator, and director of the Chronobiology and Sleep Institute. She uses Drosophila genetics to uncover basic mechanisms of circadian rhythms and sleep.

RELATED EPISODE:

• M&M 257: Sleep, Mitochondrial Metabolism & Oxidative Stress | Gero Miesenbock

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The science, hype, and unknowns surrounding popular peptides like BPC-157 & TB-500 ("Wolverine stack") for injury recovery & tissue repair.

Nick & Dr. Flynn McGuire discuss the surge in peptide use for injury recovery. They cover peptide basics, the preclinical evidence for BPC-157 and TB-500, mechanisms like angiogenesis and tissue repair, the lack of robust human trials, sourcing risks, regulatory bans, and the gap between anecdotal reports and scientific certainty.

TOPICS DISCUSSED:

• Peptide basics: Short amino acid chains (e.g., insulin, GLP-1 agonists); BPC-157 derived from gastric juice, TB-500 a fragment of thymosin beta-4.
• Rise in popularity: Driven by podcasts, social media, biohacking culture, and post-COVID distrust in institutions; “bro science” often precedes formal research.
• BPC-157 mechanisms: Pleiotropic effects including VEGF upregulation, nitric oxide pathways, angiogenesis, reduced fibrosis, and possible neuromuscular stabilization.
• TB-500 & “stacking”: Often combined with BPC-157 for presumed synergy; marketed as “Wolverine stack” for rapid healing.
• Evidence limitations: Strong rodent data for tendon/muscle repair, but almost no high-quality human trials; one small retrospective study and ongoing phase 2 trial in China.
• Safety and risks: Unknown long-term effects, potential cancer concerns via angiogenesis; no established dosing, potency, or administration route in humans.
• Sourcing & quality issues: Often obtained as “research chemicals” online; variable purity, stability concerns, no reliable regulation or third-party verification for most users.

ABOUT THE GUEST: Flynn Mcguire, MD is a physical medicine and rehabilitation resident at the University of Utah; he conducts clinical work in neurologic recovery and musculoskeletal care and has authored a narrative reviews on peptides for musculoskeletal healing.

RELATED EPISODE:

• M&M 252: Scarring, Fibrosis, Oxidative Stress, and Psilocybin & Aging | Louise Hecker

Reference Paper:

• Paper | Regeneration or Risk? A Narrative Review of BPC-157 for Musculoskeletal Healing

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Biology of obesity resistance and factors influencing weight gain in humans and animals.

TOPICS DISCUSSED:

• Historical views on obesity: In some cultures, like northern Africa or Stone Age societies, high body fat signaled status or attractiveness due to food scarcity, unlike today’s focus on leanness amid calorie abundance.
• Energy balance components: Metabolizable energy (95% absorption on average, but varying 1-11%) and unabsorbed nutrients excreted as waste significantly influence weight.
• Obesity resistance in animals: Inbred mouse strains show wide variation in weight gain on high-fat diets, often somewhat uncoupled from overeating, suggesting roles for feed efficiency, energy expenditure, or waste rather than intake alone.
• Genetic & twin studies: Monozygotic twins overfed 1,000 extra calories daily vary widely in weight gain (4-13 kg), indicating genetic influences, while mouse litter size affects lifelong obesity propensity via early-life programming.
• Bloodborne factors & hormones: Parabiosis studies led to leptin’s discovery for defending against weight loss, but evolutionary logic suggests systems also prevent excess gain, though modern environments may weaken this.
• Human thinness research: Constitutionally thin people snack more, move less, yet have better cardiometabolic health, but we don’t yet understand why.
• GLP-1 drugs & future directions: These slow gut transit and suppress appetite, but obesity’s root causes remain unclear; emerging thinness studies could inform prevention beyond drugs.

ABOUT THE GUEST: Jens Lund, PhD is a postdoctoral researcher at the University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research.

RELATED EPISODE:

• M&M 132 | Obesity Epidemic, Diet, Metabolism, Saturated Fat vs. PUFAs, Energy Expenditure, Weight Gain & Feeding Behavior | John Speakman

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Mitochondria in human evolution, climate adaptation, maternal genetics, aging, and disease.

TOPICS DISCUSSED:

• Endosymbiotic theory: Mitochondria arose from oxidative bacteria engulfed by archaea-like hosts, confirmed by phylogenetic analysis.
• Maternal mtDNA inheritance: Mitochondrial DNA is inherited from the mother, not the father. There are adaptive reasons for this.
• Haplogroups & adaptation: Tropical lineages tightly couple energy production for efficiency; northern ones uncouple to generate heat.
• Heteroplasmy & aging: Mixed mutant and normal mitochondria accumulate in cells, eroding energy in high-demand tissues like brain and heart.
• Bioenergetics in disease: Many common conditions, from Parkinson’s to cancer, stem from mitochondrial-nuclear interactions rather than nuclear genes alone.
• Ketogenic diets: High-fat intake fuels mitochondrial beta-oxidation, which may compensate for brain energy deficits in epilepsy and bipolar disorder.
• Warburg effect: Cancer cells shift to glycolysis to prioritize biosynthetic building blocks over maximal ATP production.
• Modern mismatches: Global travel pairs ancestral mtDNA with mismatched diets and climates, raising risks for metabolic dysfunction.

ABOUT THE GUEST: Douglas Wallace, PhD is a geneticist and evolutionary biologist who has studied mitochondria for over 50 years. He currently directs the Center for Mitochondrial and Epigenomic Medicine at Children’s Hospital of Philadelphia and the University of Pennsylvania.

RELATED EPISODE:

• M&M 260 | Energy Resistance Principle in Life, Healing & Disease | Martin Picard & Nirosha Murugan

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Role of bile acids in cholesterol regulation, digestion & metabolic diseases like diabetes.

TOPICS DISCUSSED:

• Bile acids basics: They enable cholesterol excretion, with about half of bodily cholesterol eliminated this way, and also aid digestion by emulsifying fats to increase enzyme access.
• Bile production & pathway: Synthesized in liver hepatocytes, bile flows via ducts to the gallbladder for storage or directly to the small intestine; post-meal, cholecystokinin triggers gallbladder contraction for fat emulsification.
• Regulation of bile acids: Self-regulated to prevent cytotoxicity, as excess can damage cell membranes; insulin and bile acids themselves influence synthesis and transport, with defects in insulin-resistant states.
• Bile acids in metabolic diseases: Increased synthesis, especially 12-hydroxylated types, occurs in type 2 diabetes and insulin resistance, potentially as an adaptation for better nutrient absorption during perceived scarcity.
• Gallbladder removal & gallstones: Common due to cholesterol supersaturation forming stones; removal eliminates concentration but preserves bile flow, reducing tolerance for high-fat meals.
• Bariatric surgery impacts: Procedures like gastric bypass increase circulating bile acids without major synthesis changes, while more extreme ones boost synthesis due to impaired intestinal sensing.
• Cholesterol homeostasis: Cells tightly regulate membrane cholesterol for fluidity and signaling; most bodily cholesterol is synthesized internally, with LDL receptors key to blood levels.
• Ongoing research: Haeusler’s lab explores manganese’s role in metabolism, bile acids in liver inflammation, and insulin’s effects on lipoproteins.

ABOUT THE GUEST: Rebecca Haeusler, PhD is an associate professor at Columbia University in the departments of medicine and pathology and cell biology, affiliated with the Naomi Berrie Diabetes Center and the Digestive and Liver Diseases Research Center.

RELATED EPISODE:

• M&M 269 | Soybean Oil: Obesity, Fatty Liver Disease, Gut Health, IBS & Colitis | Frances Sladek

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How the body's internal circadian clocks regulate metabolism, energy balance, and health.

TOPICS DISCUSSED:

• Master circadian clock in the brain: Light detection via retina entrains the suprachiasmatic nucleus, which coordinates body-wide rhythms; intrinsic period slightly deviates from 24 hours, allowing seasonal flexibility.
• Peripheral clocks in organs: Nearly all cells have autonomous clocks; liver and fat clocks rapidly adjust to feeding time, while brain clock aligns more tightly to light.
• Clock mutations and metabolism: Disrupting core clock genes (e.g., CLOCK, BMAL1) causes obesity, liver fat accumulation, and impaired insulin secretion without hyperinsulinemia.
• Timing of food intake: Eating the same high-fat calories during rest phase causes more weight gain than during active phase due to differences in energy dissipation.
• Modern disruptions (jet lag, shift work, blue light): Create desynchrony between brain and peripheral clocks, contributing to metabolic issues; late-night eating impairs glucose handling.
• Critical illness & feeding: Tube feeding at night (opposite natural cycle) induces rapid insulin resistance, highlighting mismatch costs.
• Hormone rhythms: Testosterone, glucocorticoids, and others peak at specific times; misalignment affects stress, reproduction, and metabolism.
• Weight loss drugs & maintenance: GLP-1 drugs reduce intake effectively, but regain involves neuroendocrine adaptations tied to brain clock pathways.

ABOUT THE GUEST: Joseph Bass, MD, PhD is Chief of Endocrinology, Metabolism and Molecular Medicine at Northwestern University Feinberg School of Medicine, Director of the Center for Diabetes and Metabolism, and a leading researcher who pioneered the link between circadian clock genes and metabolic disorders including obesity and diabetes.

RELATED EPISODE:

• M&M 237 | Circadian Biology: Genetics, Behavior, Metabolism, Light, Oxygen & Melatonin | Joseph Takahashi

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Gene regulation through RNAs, the neurobiology of opioid addiction, and how psychedelics affect drug-seeking by modulating inflammation and plasticity. Not medical advice.

TOPICS DISCUSSED:

• Gene regulation basics: DNA transcribes to RNAs, including non-coding types like microRNAs that inhibit mRNA translation into proteins, influencing up to 60% of the proteome.
• Non-coding RNAs in neuroplasticity: MicroRNAs and circular RNAs regulate synaptic changes, with activity-induced ones like miR-485-5p linked to rapid responses in drug cue memory and addiction reinforcement.
• Opioid addiction models: Rats self-administer heroin or fentanyl via levers, showing compulsive seeking; fentanyl’s higher potency drives faster learning but similar long-term effects to heroin when doses are equated.
• Differences between opioids: Heroin and fentanyl both activate mu-opioid receptors for euphoria and dopamine release, but fentanyl lingers longer; no major behavioral differences in seeking once potency is matched.
• Psilocybin’s effects on addiction: A single psilocybin dose post-abstinence reduces heroin-seeking in rats by dampening neuroinflammation in brain regions like the nucleus accumbens and prefrontal cortex.
• Brain Inflammation: Opioids induce pro-inflammatory changes via cytokines like IL-17A and pathways like TNF-alpha, leading to glial activation and blood-brain barrier leaks; psilocybin counters this.
• MicroRNA biomarkers: Blood microRNAs reflect gene expression patterns tied to disease states, with potential to predict opioid relapse risk, treatment response, or neonatal withdrawal severity non-invasively.
• Future research: Ongoing work links psilocybin’s serotonin 2A activation to anti-inflammatory gene changes, plus human studies on microRNAs for personalized addiction treatments.

ABOUT THE GUEST: Stephanie Daws, PhD is an associate professor at Temple University in the Center for Substance Abuse Research and Department of Neurosciences, where she researches mechanisms of drug-seeking behavior with a focus on opioids and psychedelics.

RELATED EPISODE:

• M&M 2 | Psilocybin, LSD, Ketamine, Inflammation & Novel Psychedelic Medicines | Charles Nichols

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The biology of fat tissue, estrogen's role in metabolism and health, and how exercise interacts with these processes, especially during menopause.

TOPICS DISCUSSED:

• Adipose tissue basics: White fat primarily stores energy in large lipid droplets, while brown fat burns fatty acids for heat via high mitochondrial density; white fat can “brown” with exercise or certain foods like capsaicin.
• Fat distribution & health: Subcutaneous fat (under skin) is more insulin-sensitive and less problematic than visceral fat (around organs), which links to metabolic issues; females store more subcutaneously pre-menopause, shifting to visceral post-menopause.
• Estrogen signaling: Estradiol binds nuclear and membrane receptors to regulate gene expression and mitochondrial function; it enhances insulin sensitivity and browning in fat cells, with receptors like ER-alpha feminizing fat distribution.
• Fat storage: Fat cells enlarge (hypertrophy) more than multiply in obesity, leading to hypoxia, inflammation, and insulin resistance; excess fatty acids spill to liver and muscle, worsening metabolic dysfunction.
• Menopause effects: Estrogen drop causes visceral fat gain, reduced energy expenditure, insulin resistance, and higher metabolic disease risk; symptoms include hot flashes and reduced exercise motivation, modeled in rodents via ovary removal.
• Exercise & estrogen links: Exercise boosts estrogen receptor expression and mitochondrial density in fat, mimicking estrogen’s browning effects; synergism may explain reduced exercise responsiveness post-menopause.
• Brain-fat connections: Estrogen in the nucleus accumbens influences exercise motivation and fat browning; manipulations there alter running behavior and adipose metabolism in rodents.

ABOUT THE GUEST: Victoria Vieira-Potter, PhD leads a lab at the University of Missouri, studying how estrogen and exercise influence adipose cells.

RELATED EPISODE:

• M&M 174 | Adipose Tissue & Body Fat: Obesity, Insulin, Leptin, Fertility, Weight Loss & GLP-1 Drugs | Sean Hartig

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The brain's mysterious claustrum region, its role in cognitive flexibility, and how substances like alcohol and psychedelics affect neural circuits and behavior. Not medical advice.

TOPICS DISCUSSED:

• Cerebral cortex structure: Described as a six-layered structure with pyramidal neurons and inhibitory interneurons; information flows between layers and regions to process sensory input and enable complex behaviors.
• Claustrum anatomy & connectivity: A sheet-like subcortical structure embedded in white matter, bidirectionally connected to cortical areas, especially prefrontal regions in rodents, with broader connections in primates and humans suggesting an integrative role.
• Claustrum function in cognition: Experiments show claustrum activation during task switches from easy to demanding modes, synchronizing cortical networks via inhibition and rebound excitation, potentially enabling flexible behavior.
• Mouse models in neuroscience: Mice are used for genetic tractability to manipulate and monitor specific circuits, revealing claustrum’s role in vigilance tasks but not simple ones.
• Alcohol’s effects on brain circuits: Chronic alcohol promotes inflexible behaviors by altering striatal interneurons and inhibitory inputs, leading to compulsive drinking despite aversive consequences.
• Psychedelics & brain networks: Psilocybin disrupts default mode and other networks, inhibits claustrum via serotonin 1B receptors, with effects persisting 24 hours, possibly contributing to therapeutic benefits.
• Evolution of claustrum: Connectivity expands from rodents to humans, shifting from cognitive-specific to broader network control, including anti-correlated states like default mode versus task-engaged.
• Integration of claustrum & basal ganglia: Claustrum funnels prefrontal signals to basal ganglia for action selection; alcohol may impair this, exacerbating inflexibility in addiction.

ABOUT THE GUEST: Brian, PhD is a professor in the Department of Pharmacology and Physiology at the University of Maryland School of Medicine, where he leads a neuroscience lab studying brain circuits underlying flexible and inflexible behaviors using mouse models, with a focus on alcohol use disorder.

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Pharmacology & neurobiology of psychedelics & MDMA, focusing on isomers, sex-specific effects, and mechanisms in animal models. Not medical advice.

TOPICS DISCUSSED:

• Biased agonism: Different drugs activate the same receptor (e.g., 5-HT2A) but trigger varied intracellular pathways, explaining why LSD is psychedelic while similar lisuride is not.
• Enantiomers & isomers: Mirror-image versions of drugs like MDMA (S and R forms) and LSD (four isomers) often produce distinct effects; only one LSD isomer is psychedelic, for example.
• MDMA isomer effects: S-MDMA induces stronger head twitches (psychedelic proxy) via serotonin release, and increases dendritic spines in male mice but not females; R-MDMA has somewhat different effects.
• Sex-specific drug responses: In mice, females show stronger psychedelic effects (head twitches) from psilocybin and DOI at the same dose, but males exhibit greater post-acute benefits like reduced opioid withdrawal.
• Psilocybin in opioid addiction models: A single dose reduces place preference for oxycodone and withdrawal symptoms in male mice more than females, with opposite spine density effects in reward-related brain areas.
• Mechanisms beyond 5-HT2A: Psychedelics involve other receptors like metabotropic glutamate receptors, forming dimers with 5-HT2A to enable dual signaling pathways; effects in subcortical regions like nucleus accumbens are 5-HT2A-independent.
• Clinical implications: Street MDMA may vary in S/R ratios, affecting experiences; clinical trials often use racemic mixtures without weight-adjusted dosing, potentially missing sex differences.

ABOUT THE GUEST: Javier Gonzalez-Maeso, PhD is a professor of pharmacology and toxicology at Virginia Commonwealth University, with a PhD in medicine from Spain focused on G-protein coupled receptors and human brain studies in depression and addiction.

RELATED EPISODE:

• M&M 230 | Psilocybin & MDMA: Inflammation, Stress & Brain-Body Communication | Michael Wheeler

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The AMP kinase pathway's role in cellular energy sensing, nutrient allocation, and its connections to health practices like fasting, exercise, and diet.

TOPICS DISCUSSED:

• Cellular energy basics: ATP/ADP/AMP as energy currencies; AMP kinase activates on low ATP to conserve and redirect resources, like a budget manager.
• AMP kinase mechanics: Heterotrimeric enzyme phosphorylating 100+ substrates; localizes dynamically in cytosol, mitochondria, nucleus to integrate signals.
• Nutrient detection: Senses fatty acids in fasting/ketogenic states, boosting fat oxidation and mitochondria independent of energy drops.
• Fasting/exercise impacts: Elevate AMP kinase for mitophagy, better fuel switching; mimic historical scarcity absent under modern constant feeding.
• mTOR relationship: AMP kinase inhibits mTOR to stop growth in low energy states; feedback loop disrupted by abundance, promoting tissue buildup.
• Disease links: Low AMP kinase in obesity/diabetes reduces flexibility; activation prevents cancer but may aid tumor survival in therapy.
• Drugs/diets: Metformin and GLP-1s like Ozempic activate AMP kinase for glucose control/weight loss; ketogenic diets activate at intermediate levels for fat efficiency.

ABOUT THE GUEST: Gregory Steinberg, PhD is a Professor of Medicine at McMaster University and co-directs the Centre for Metabolism, Obesity, and Diabetes Research, focusing on cellular energy sensors like AMP kinase.

RELATED EPISODE:

• M&M 260 | Energy Resistance Principle in Life, Healing & Disease | Martin Picard & Nirosha Murugan

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How industrial farming, seed oils, soy, and pesticides impact food nutrition and health. Not medical advice.

TOPICS DISCUSSED:

• Soy’s rise in farming: Originating from paint uses and wartime chemicals, soy became dominant due to subsidies and large-scale farming practices, but introduces high PUFAs, phytoestrogens, and pesticides into animal feeds.
• Feed’s impact on eggs: Chicken feeds high in soy and corn raise linoleic acid levels in eggs compared to low-soy alternatives; low-PUFA eggs improve digestibility for many.
• PUFAs & health effects: Feeding PUFAs fattens animals faster and disrupts human gut lining and metabolism; body fat composition changes take time, linking to chronic issues like low energy.
• Phytoestrogens in soy: These compounds pass into animal products, affecting estrogen signaling and gut health; mainstream nutrition often overlooks their risks despite historical low exposure.
• Dairy variations: Raw milk retains lactoferrin for iron regulation and gut support, plus enzymes and probiotics destroyed in pasteurization; it may resolve dairy intolerances for some.
• Regenerative farming model: Armstrong’s cooperative emphasizes traditional feeds to “resaturate” foods, reducing PUFAs; supports small farms amid declining farm numbers.
• Ancestral diets insight: Traditional diets vary but share low PUFA levels, avoiding modern chronic illnesses tied to industrial fats.

ABOUT THE GUEST: Ashley Armstrong, PhD co-founded Angel Acres Farm in Michigan and now runs Nourish Food Club, a cooperative of small farms producing low-PUFA, soy-free animal foods.

RELATED EPISODE:

• M&M 273: Nutrition Content of Animal & Plant Foods: Beef, Plant-Based Meat, Raw vs. Processed Milk

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How individuals vary in responses to carbs, fibers, and fats.

TOPICS DISCUSSED:

• Personalized health profiling: Snyder’s lab sequences genomes and measures molecules from blood, urine, and microbiomes to detect diseases early, emphasizing data-driven discovery over assumptions.
• Fiber variations and effects: Responses to dietary fibers vary individually, with microbiome playing a key role.
• Glycemic responses to carbs: People spike differently to foods like rice, potatoes, or bread; tied to insulin resistance subtypes in muscles, liver, or pancreas.
• Type 2 diabetes heterogeneity: 90% of diabetes cases are type 2 with subtypes like muscle or hepatic resistance; triggers include genetics and infections, with prediabetes often undetected.
• Continuous glucose monitors (CGMs): Affordable tools measure glucose every five minutes, revealing personal food triggers; spikes link to risks like cardiovascular disease and cancer.
• Lipidomics: Lipids are diverse, serving as energy sources, structural components, and signaling molecules; understudied but key in metabolism and gene expression.
• Maternal health & pregnancy: Metabolomics shows thousands of changes, including hormone shifts; cord blood analysis reveals fetal nutrient use and drug transfers, with markers for preterm birth or healthy outcomes.
• Future research: Exploring epigenetic changes in diabetes, personalized nutrition mitigation, and digital markers from wearables for mental health tied to diet and gut-brain axis.

ABOUT THE GUEST: Michael Snyder, PhD is the Stanford W. Ascherman Professor of Genetics and former chair of the Department of Genetics at Stanford University School of Medicine, where he directs the Center for Genomics and Personalized Medicine.

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How agricultural practices influence the nutrient density of foods, particularly meat, and the importance of hidden compounds beyond standard nutrition labels.

TOPICS DISCUSSED:

• Nutrient density profiling: Labs analyze thousands of compounds beyond macros and vitamins; this “dark matter” includes phytonutrients that may support health despite not being essential.
• Phytonutrients in foods: Plant secondary metabolites like polyphenols act as antioxidants and influence pathways like mTOR; animals convert plant compounds into bioactives humans access via meat.
• Red meat definition: Refers to meats high in myoglobin, including beef and lamb; most meats are red in wild forms, but human intervention affects color and classification.
• Ruminant animals: Animals like cows that have multi-chambered stomachs to digest plants; this metabolism differs from non-ruminants (e.g. chickens), affecting nutrient profiles in their meat.
• Grass-fed vs. grain-fed beef: Grass-fed has higher omega-3 fats and phytonutrients from diverse plants; studies show it improves human omega-6:3 ratios and biomarkers from grass-fed, pastured-raised animals.
• Farming practices & variations: Plant diversity boosts beef nutrients.
• Upcoming research: Long-term trials on effects of pasture-raised foods on human health; interactive dashboards for farmers to profile nutrients and inform policy.

ABOUT THE GUEST: Stephan Van Vliet, PhD is an Assistant Professor in the Department of Nutrition, Dietetics, and Food Sciences at Utah State University, where he directs the Center for Human Nutrition Studies, focusing on linking food production systems to nutrient profiles and conducting clinical trials on health impacts.

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Cellular metabolism, mitochondrial health, and the roles of diet and environment in metabolic health, fetal & child development, and Alzheimer's.

TOPICS DISCUSSED:

• Cellular growth vs. burning: Cells alternate between growing (using glucose for building blocks in low-oxygen environments) and burning (generating ATP in mitochondria with oxygen); dysregulation leads to metabolic issues.
• Key regulatory enzymes: PI3 kinase imports glucose, AMP kinase builds mitochondria, and mTOR drives cell division; their synchronization determines healthy modes, while desynchronization causes diseases.
• Fructose as a dose-dependent mitochondrial toxin: High fructose intake inhibits AMP kinase, reducing mitochondrial function and diverting energy to fat storage; it is dose-dependent, like alcohol, and unnecessary in the diet.
• Obesogens & endocrine disruptors: Chemicals like tributyltin (TBT) alter gene expression across generations, promoting obesity unrelated to calories; modern exposures increase reactive oxygen species (ROS), burdening cells.
• Fetal & neonatal development: Maternal diet, especially high sugar or formula feeding, can cause neonatal obesity and fatty liver; breastfeeding supports proper jaw development and oxygen intake.
• Brain metabolism & Alzheimer’s: The brain’s high energy needs make it vulnerable to mitochondrial issues and ROS; energy deficits from diet, stress, and toxins lead to synapse loss and inflammation, treatable via prevention.
• ROS & health: Mitochondria produce ROS as a byproduct of ATP generation; excess from diet or environment causes damage, but antioxidants and lifestyle can mitigate risks.

PRACTICAL TAKEAWAYS:

• Limit added sugars in your diet to reduce mitochondrial stress and ROS, focusing on whole foods over ultra-processed items for better metabolic health.
• Prioritize breastfeeding for infants when possible to support proper physical development and reduce future metabolic risks.
• Incorporate regular exercise and social activities to manage stress and boost brain-protective factors like BDNF, aiding neurodegeneration prevention.
• Get adequate sleep to regulate cortisol and maintain cellular energy balance, helping prevent brain fog and chronic diseases.

ABOUT THE GUEST: Robert Lustig, MD is a pediatric endocrinologist and Professor Emeritus at the University of California, San Francisco, with a background in neuroendocrinology and obesity research.

*Not medical advice.

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Deep dive into how ketogenic diets and carbohydrate intake effect exercise performance, and misconceptions in sports nutrition.

TOPICS DISCUSSED:

• Insulin as a powerful metabolic hormone: regulates nutrient storage across tissues, overriding others like glucagon to promote fat and glucose storage during abundance.
• Glucagon & GLP-1 roles in metabolism: Glucagon mobilizes liver glucose during scarcity; GLP-1, amplified in drugs like Ozempic, suppresses hunger but originated as a diabetes treatment.
• Transition to ketosis in fasting or low-carb diets: Low insulin enables fat breakdown into ketones for brain fuel, allowing survival for weeks without food, with adaptation taking about four weeks.
• Hypoglycemia vs. glycogen depletion: Low blood sugar causes fatigue and irritability due to brain energy deficit, while muscle glycogen levels do not directly limit performance.
• Ketogenic diets & exercise performance: Studies show no difference in endurance after adaptation, with some athletes performing better on low-carb due to enhanced fat oxidation.
• High-carb diets in athletes: In one study, about 30% developed prediabetes-like fasting glucose elevations, linked to total carb intake, despite leanness and fitness.
• Misconceptions in sports nutrition: Guidelines recommend 60-90g carbs/hour, but evidence shows 10g suffices to maintain blood sugar and performance, avoiding insulin spikes that impair fat use.
• Individual variability in diet response: Athletes vary in optimal fuel sources; it’s possible to by athletic and lean but also metabolically unhealthy.

PRACTICAL TAKEAWAYS:

• For workouts over ~60 minutes, consume ~10g carbs per hour (e.g., a third of a banana) to maintain blood sugar and prevent fatigue, regardless of overall diet.
• Allow at least four weeks for adaptation when trying a ketogenic diet, enabling the body to fully transition to the ketogenic state.
• Monitor personal responses to carb intake, as high levels can elevate fasting glucose even in fit individuals; consider lower-carb options if experiencing metabolic issues.
• Prioritize metabolic flexibility through varied diets or fasting periods to improve energy stability, but consult resources for proper formulation to support health.

ABOUT THE GUEST: Andrew Koutnik, PhD earned a PhD in biomedical sciences with a focus on exercise physiology and metabolic health, informed by his personal diagnosis of type 1 diabetes in childhood.

*Not medical advice.

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Neurobiology of maternal care in mammals: hormonal influences, stress effects & a study on psilocybin's unexpected effects during the postpartum period.

Sponsor: SporesMD. Use code TRIKOMES for 20% off pharmaceutical-grade mushroom liquid cultures & mycology products.

Topics Discussed:

• Maternal care behavior in rodents: Nursing, pup retrieval, grooming, and nest-building, essential for altricial pups’ survival; conserved across mammals but varies by species.
• Hormonal changes in pregnancy: Estradiol and progesterone surge then drop at birth, crossing the blood-brain barrier to enable infant attraction and care via gene expression and neuroplasticity.
• Brain circuitry for parenting: Medial preoptic area acts as a central hub, coordinating motivation and sensory inputs; present in both sexes but activated differently by hormones and experience.
• Stress impacts on mothers: Social stressors like male intruders dysregulate care, leading to frantic behaviors and avoidance; models human psychosocial stress linked to postpartum mood disorders.
• Sex differences in pup care: Mothers groom male pups more, influencing sexual behaviors, which effects future behavior.
• Psilocybin in postpartum mice: Single dose increased anxiety in mothers, showed no antidepressant effects, and transferred via milk, causing long-term anhedonia and impairments in offspring as adults.
• Serotonin system development: Early exposure to serotonergic drugs like psilocybin or SSRIs alters lifelong behavior, highlighting sensitive periods in brain reorganization.

Practical Takeaways:

• Reduce postpartum stress through social support to enhance maternal bonding and minimize mood disorder risks.
• Approach psychedelics cautiously during postpartum due to potential anxiety increases and offspring effects via milk.
• Recognize hormonal shifts heighten sensitivity to infant cues, aiding natural caregiving instincts.
• Monitor environmental factors like food availability or threats that could disrupt parental behaviors in high-stress scenarios.

About the guest: Danielle Stolzenberg, PhD is an associate professor of psychology at the University of California, Davis, where her lab studies the neurobiology of maternal care.

Reference Paper:

• Study: Psilocybin during the postpartum period induces long-lasting adverse effects in both mothers and offspring

Related Episode:

• M&M 180: Mother-Infant Bonding, Maternal Care & Breastfeeding, Neural Basis of Hunger & Social Behavior | Marcelo Dietrich

*Not medical advice.

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Metabolic effects of soybean oil and linoleic acid on obesity, fatty liver, and liver function.

Topics Discussed:

• Historical trends in soybean oil use: Consumption increased dramatically since the 1960s due to farming subsidies, now providing over 10% of calories for many Americans, far exceeding the 1-2% required biologically.
• Soybean oil’s effects in mice: Diets with 8-10% linoleic acid cause obesity, fatty liver, and diabetes over weeks, unlike coconut oil diets; effects persist even after diet switch unless combined with fasting.
• Role of HNF4 protein: This conserved liver transcription factor binds linoleic acid, regulating gene expression for metabolism; variants shift between carbohydrate and fat processing, with imbalances linked to fatty liver and cancer.
• Oxylipins from linoleic acid: Conversion in liver drives obesity; mice unable to produce them resist weight gain on soybean oil, suggesting these metabolites are key culprits.
• Vitamin B1 & soybean oil: Diets deplete B1 in liver and blood, contributing to obesity; supplementation with B1 analogs prevents weight gain, unlike beef tallow diets which preserve B1 levels.
• Gut & microbiome impacts: Soybean oil alters gut bacteria, potentially reducing B1 production and increasing permeability, leading to inflammation; farm animals fed soybean meal pass effects to consumers.
• Broader health implications: Reanalysis of old human studies questions linoleic acid’s heart benefits; focus on reducing processed foods and seed oils, while noting olive oil’s advantages from historical contexts.

Practical Takeaways:

• Limit processed foods and seed oils like soybean to reduce linoleic acid intake, aiming for 1-2% of calories; read labels and opt for olive oil or home-cooked meals.
• Incorporate intermittent fasting, such as 12-16 hours without eating daily, to help reverse obesity effects from high-linoleic diets, based on mouse reversibility studies.
• Choose grass-fed or naturally fed animal products to avoid indirect soybean oil exposure from feed, potentially preserving nutrient levels like vitamin B1.
• Monitor diet when traveling or changing habits, as shifts in oil types can affect medication metabolism via liver enzymes.

About the guest: Frances Sladek, PhD is a professor whose research focuses on the nuclear receptor HNF4 and the health impacts of dietary fats, particularly soybean oil.

*Not medical advice.

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How seasonal changes in light and dietary unsaturated fats affect circadian rhythms in mammals.

Topics Discussed:

• Evolutionary context of circadian rhythms: All organisms have adapted to Earth’s 24-hour day for survival, with internal clocks slightly offset and adjusted by environmental cues.
• Molecular clock mechanism: Involves a feedback loop where proteins turn on/off genes, lasting ~24 hours, regulated by phosphorylation and degradation for timing precision.
• Genetic variations in sleep: Families with mutations in clock genes like PER2 cause extreme morning lark behavior, altering protein stability and period length by hours.
• Light entrainment: Morning light shortens human clocks (average 24.2 hours) to match 24-hour days; seasonal day length changes require gradual adjustments.
• Food & metabolic links: Seasonal food scarcity/abundance affects clock via glucose and fatty acids competing for protein modifications, as shown in diabetic mouse models.
• Role of unsaturated fats: Paper finds MUFA/PUFA ratios in diet alter phosphorylation of clock proteins, speeding or slowing adaptation to winter/summer light cycles in mice.
• Modern environmental impacts: Artificial light extends “daytime” signals, while constant food access erases seasonal patterns, contributing to obesity and diabetes risks.
• Jet lag & adaptations: Sudden time shifts mimic seasonal experiments; high-sugar/fat intake may phenocopy genetic effects to aid adjustment, though not recommended for health.

Practical Takeaways:

• Expose yourself to morning natural light to help synchronize your internal clock and improve daily energy.
• Consume main meals during daylight hours and avoid late-night eating to align with natural metabolic rhythms.
• Limit evening screen time to reduce artificial blue light disrupting sleep onset.
• Consider varying diet seasonally, favoring diverse, whole foods to mimic natural availability patterns for better health.

About the guest: Louis Ptacek, MD is a neurologist and professor at the University of California, San Francisco. He researches inherited neurological diseases and sleep traits, including genetic variations causing extreme early rising.

Related Episode:

• M&M 237: Circadian Biology: Genetics, Behavior, Metabolism, Light, Oxygen & Melatonin | Joseph Takahashi

*Not medical advice.

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How ketosis and ketogenic diets work and how these tools can improve metabolic health, brain function, and even cancer management.

Topics Discussed:

• Organs have different fuel preferences: brain strongly prefers glucose, heart prefers fatty acids, skeletal muscle is flexible and likes fat/ketones.
• Humans evolved with high metabolic flexibility; regular ketosis was normal for ancestors, but today most people never experience it.
• “Keto flu” is largely glucose withdrawal plus electrolyte/sodium loss; proper salt and hydration prevent most symptoms.
• Classic medical ketogenic diet is ~90% fat (historically saturated); modern versions often use more monounsaturated fats, MCTs, and higher protein.
• Saturated fat is not inherently atherogenic in the context of weight stability or caloric deficit; excess calories from any source can dysregulate metabolism.
• Exogenous ketones (e.g. BHB) provide energy, reduce ROS, stabilize membranes, increase inhibitory tone (GABA), and have hormone-like signaling effects independent of diet.
• Cancer cells often show Warburg effect (damaged mitochondrial respiration → heavy reliance on glycolysis); lowering glucose and raising ketones can stress cancer cells.
• True keto-adaptation for athletic performance requires 6–12 weeks; after that, elite athletes can match or exceed prior high-carb performance at sub-maximal and endurance efforts.

Practical Takeaways:

• Therapeutic carbohydrate restriction (50–100 g/day for many people) plus occasional fasting or ketone supplements can restore metabolic flexibility with far fewer side effects than strict keto.
• Prioritize whole-food fats (eggs, fatty fish, beef, olive oil, butter/lard) and minimize processed keto products loaded with seed oils.
• Supplementing BHB (salts or esters) or MCT oil can ease the transition into ketosis, boost ketones without strict dieting, and may support brain and metabolic health.
• Regularly check basic blood markers (glucose, lipids, electrolytes) and consider an OmegaQuant test; optimizing metabolic health is one of the strongest preventable steps against cancer, neurodegeneration, and heart disease.

Supplemental Ketone (BHB):

• KetoCitra—Ketone body BHB with potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off.

*Not medical advice.

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How dietary polyunsaturated fats, especially omega-6 from seed oils, influence inflammation & heart health.

Topics Discussed:

• Polyunsaturated fatty acids (PUFAs): Omega-6 from seed oils like safflower and corn can convert to pro-inflammatory molecules, while omega-3s produce resolving ones; imbalance biases toward chronic inflammation.
• Inflammation regulation: Acute inflammation aids healing but requires active “on” and “off” signals from lipid mediators; chronic inflammation arises from excess omega-6, delaying resolution.
• Heart health & diet: High omega-6 diets worsen post-heart attack outcomes in mice by elevating pro-inflammatory lipids.
• Evolution & historical context: PUFAs are essential but naturally balanced in pre-industrial diets; modern processing skews ratios, contributing to diseases, as shown in early rat experiments needing minimal fats for survival.
• Aging & lifestyle factors: Excess omega-6 exacerbates inflammation in older mice; sleep, exercise, and balanced fats are crucial for metabolic health and enzyme function in processing lipids.
• Cannabis & omega-6 interaction: In mice on high omega-6 diets, CBD-rich cannabis smoke reaches the heart quickly, suppresses immune response, and weakens cardiac strain, unlike in balanced-diet controls.
• Genetic models: FAT-1 mice converting omega-6 to omega-3 show better healing and neuroprotection; FAT-2 mice doing the opposite exhibit liver fibrosis and metabolic issues, highlighting omega-6 excess harms.

Practical Takeaways:

• Balance omega-6 and omega-3 intake by reducing seed oils in processed foods and increasing sources like fish or algae to support inflammation resolution and heart health.
• Monitor and adjust fat intake with age, as older individuals are more sensitive to omega-6 excess leading to immune dysregulation.
• Avoid combining high omega-6 diets with smoking, as it may impair immune and cardiac responses based on animal data.

About the guest: Ganesh Halade, PhD is a cardiovascular scientist and associate professor at the University of South Florida Morsani College of Medicine.

*Not medical advice.

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Methods & challenges of establishing causal relationships in health research, emphasizing epidemiology, randomized trials, and genetic approaches.

Topics:

• Epidemiology: Studies disease influences using observational designs like case-control and prospective cohorts, plus trials, to identify patterns and test hypotheses.
• Hierarchy of evidence critique: Rejects rigid pyramids favoring RCTs, as all studies can be biased; advocates triangulation integrating varied data types for robust conclusions.
• RCT strengths & weaknesses: Randomization balances confounders, but issues like poor blinding, attrition, or subversion can undermine results; large samples may yield spurious precision if biased.
• Confounding & reverse causation: Examples include yellow fingers and lung cancer (both from smoking) or early atherosclerosis inflating CRP-disease links; hard to fully control statistically.
• Nutrition epidemiology: Observational studies often overstate benefits (e.g., vitamin E for heart disease), leading to failed trials; incentives favor new findings over revisiting errors.
• Mendelian randomization: Uses genetic variants as proxies for exposures (e.g., ALDH2 for alcohol metabolism) to mimic randomization; reveals no heart benefits from alcohol, unlike observational data.
• Negative controls: Tests implausible outcomes (e.g., smoking and murder) or exposures (e.g., paternal smoking in pregnancy) to check for confounding artifacts.
• Evidence triangulation: Combines diverse studies with different biases (e.g., cross-cultural comparisons) for causality; applied to dismiss HDL-raising drugs despite initial promise.

Practical Takeaways:

• Scrutinize health claims by checking for negative controls or variety in evidence sources to avoid mistaking correlation for causation.
• For personal decisions like alcohol intake, consider genetic studies showing risks at all levels, and aim for moderation or abstinence based on overall evidence.
• When evaluating supplements or diets, prioritize trials over observational data, and question media hype that ignores confounding factors.

About the guest: Dr. George Davey Smith, MD, DSc is a professor of clinical epidemiology at the University of Bristol and director of the MRC Integrative Epidemiology Unit.

*Not medical advice.

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Integration of brain metabolism with neural signaling, highlighting how core metabolites regulate energy use and protect neurons.

Topics Discussed:

• Brain energy efficiency: Brains are much more energy-efficient than computers for similar processing, relying on adaptive metabolic strategies evolved under energy scarcity.
• Metabolism vs. information processing: Core metabolites like glutamate bridge basic cellular energy production and neural signaling.
• Lactate as a signal: Produced during exercise, lactate diffuses from muscles to brain, modulating neuronal excitability and providing neuroprotection.
• BHB in ketosis: During fasting or ketogenic diets, beta-hydroxybutyrate displaces glucose as fuel, enhances antioxidant defenses, and activates protective potassium channels in neurons.
• Adenosine and sleep: Accumulates from ATP breakdown during wakefulness, triggering sleep and locally inhibiting overactive neural networks for energy conservation.
• Glial cells’ role: Astrocytes and oligodendrocytes handle sophisticated metabolism, release signaling molecules like lactate, and modulate synapses, and influence diseases like Alzheimer’s.

Practical Takeaways:

• Regular exercise elevates lactate, which signals the brain to adapt metabolism and may enhance neuroprotection against stress.
• Intermittent fasting or ketogenic diets can induce ketosis with BHB, potentially boosting brain antioxidant defenses and preconditioning against metabolic stress.
• Prioritizing sleep helps clear adenosine buildup, restoring energy balance and supporting long-term neural health.

About the guest: Dr. Luis Felipe Barros, MD, PhD is a Chilean neurobiologist and professor at the Universidad de Valparaíso, where he leads a lab studying brain metabolism from glucose transport to mitochondrial function.

Related Episode:

• M&M 255 | Unlocking Energy: How Nutrition & Drugs Impact Your Mitochondria | Chris Masterjohn

*Not medical advice.

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Mitochondrial fatty acid synthesis is a little-known but essential pathway that supports energy production and metabolic health.

Summary: Dr. Sara Nowinski explains how mitochondria not only burn fuels to make ATP but also synthesize their own fatty acids inside the matrix; this conserved pathway produces lipoic acid (an essential enzyme cofactor) and longer-chain fats required for proper assembly of the electron transport chain, and disrupting it impairs respiration, glucose handling, and insulin sensitivity while enhancing it appears protective against obesity and heart injury.

About the guest: Sara Nowinski, PhD is an assistant professor in the Department of Metabolism and Nutritional Programming at Van Andel Institute in Grand Rapids, Michigan, where since 2021 she has led a lab focused on mitochondrial biology and the mitochondrial fatty acid synthesis (mitoFAS) pathway.

Topics Discussed:

• Basic mitochondrial energy production: food → pyruvate/fatty acids → acetyl-CoA → TCA cycle → electron transport chain → ATP
• Mitochondrial fatty acid synthesis (mitoFAS): a bacterial-like pathway that builds fats on an acyl carrier protein inside the matrix
• Lipoic acid: an 8-carbon fatty acid made only by mitoFAS, covalently attached to key enzymes (e.g., pyruvate dehydrogenase); cannot be rescued by supplements for cofactor use
• Longer mitoFAS products (14–16 carbons) stabilize electron transport chain assembly factors, explaining why pathway loss collapses respiration even when lipoic acid is intact
• Knocking out mitoFAS causes embryonic lethality, insulin resistance, poor glucose homeostasis, and a rare neurodegenerative disorder (MEPAN syndrome)
• Overexpressing the mitochondrial acyl carrier protein protects mice from diet-induced obesity, insulin resistance, and cardiac injury
• Muscle cell differentiation fails without mitoFAS, hinting at a role in tissue development and repair

Practical Takeaways:

• Supplemental lipoic acid can act as an antioxidant but cannot replace the lipoic acid your mitochondria must make themselves for enzyme function.
• Severe impairment of mitochondrial fatty acid synthesis is linked to insulin resistance and metabolic disruption, suggesting mitochondrial health (beyond just biogenesis) matters for glucose control.

*Not medical advice.

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How internal states like hunger and hormones shape instinctive behaviors, particularly parental care

Episode Summary: Dr. Johannes Kohl explains instinctive behaviors in mammals, emphasizing how states like hunger and hormonal cycles modulate actions such as parental care; they discuss hypothalamic circuits, hormone integration, and pregnancy-induced brain changes, highlighting the balance between motivations like feeding and nurturing offspring.

About the guest: Jonny Kohl, PhD heads the State-Dependent Neural Processing Lab at the Francis Crick Institute in London.

Discussion Points:

• Instinctive behaviors: Pre-wired actions like escaping predators or parental care enable survival without learning, yet remain modifiable by experience and internal states.
• Internal states: Defined as slowly changing conditions (minutes to weeks) like hunger or hormonal fluctuations that influence brain processing & behavior prioritization.
• Hunger regulation: Hypothalamic AGRP neurons detect caloric deficits, creating motivational discomfort relieved by food anticipation, operating on multiple timescales via neurotransmitters & peptides.
• Parental care: Virgin mice show variable pup-directed behaviors; hunger increases aggression, modulated by estrous cycle hormone ratios (estradiol/progesterone).
• Hormone-brain interactions: Steroid hormones like estradiol and progesterone diffuse into the brain, altering gene expression, neuronal excitability, and circuit plasticity over short and long timescales.
• Pregnancy adaptations: Late pregnancy rewires MPOA circuits via surging hormones, preparing robust maternal behavior before birth (anticipatory brain plasticity).

Practical Takeaways:

• Recognize hunger’s impact: Mild food deprivation can heighten irritability or aggression, which can affect social interactions.
• Consider hormonal influences: Cyclical hormone changes affect mood and motivation; tracking cycles may help predict and manage behavioral shifts.
• Prioritize self-care in parenting: Sleep and nutrition deficits mimic hunger states, potentially reducing patience; ensure rest and meals to support nurturing behaviors.
• Question chronic hormone use: Long-term interventions like birth control or testosterone can alter brain function; weigh benefits against potential side effects.

*Not medical adv

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How mitochondria travel between cells and how this hidden communication shapes metabolism, immunity, and even potential therapies.

Episode Summary: Dr. Jon Brestoff talks about mitochondrial dynamics inside cells, their transfer between unrelated cells (distinct from inheritance during division), and its roles in adipose tissue communication, macrophage cleanup, and systemic metabolic signaling; they explore how high-fat diets disrupt this process, potential hormetic benefits, therapeutic mitochondria transplantation for diseases like Leigh syndrome and obesity, and broader immunometabolism crosstalk.

About the guest: Jon Brestoff, MD, PhD is an associate professor of pathology and immunology at Washington University School of Medicine in St. Louis, where he directs the Initiative for Immunometabolism.

Discussion Points:

• Mitochondria per cell range from ~100-5000; they move via fusion/fission, vertical inheritance (cell division), or horizontal transfer without division.
• Transfer mechanisms: free release, extracellular vesicles, or tunneling nanotubes using cytoskeleton transport.
• In healthy fat tissue, adipocytes routinely donate mitochondria to macrophages for degradation (quality control); high-fat (lard-based, long-chain FA) diets block macrophage uptake, diverting mitochondria to other organs.
• Diverted mitochondria may induce “mito-hormesis” (mild oxidative stress boosting antioxidants) or signal adipocyte metabolic status inter-organ.
• Mitochondria transplantation shows promise in animal models for ischemia-reperfusion, obesity, and mitochondrial diseases.
• Immune cells prefer glycolysis but have low mitochondrial biomass; transplanted mitochondria tilt T-cells toward anti-inflammatory regulatory phenotype.
• Circulating cell-free mitochondria rival immune cell numbers.
• Obesity inflammation stems from dying oversized adipocytes releasing lipids/mitochondria, forming crown-like structures with pro-inflammatory macrophages.
• Leigh syndrome from genetic mutations disrupting the electron transport chain.
• Transfer may be an evolutionary relic of endosymbiosis; cells may selectively use exogenous mitochondria like a “generator” during metabolic crisis.

Reference Paper:

• Study: The power and potential of mitochondria transfer

Related Episode:

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A biophysical rethink of life, health, and disease through the lens of the Energy Resistance Principle (ERP).

Episode Summary: A reframe of biology as energy flow through resistance rather than mere molecular machinery, introducing the Energy Resistance Principle (ERP): life requires a Goldilocks balance of electron flow from food to oxygen via mitochondria; too much or too little resistance drives aging, disease, and death. Explain mitochondria as energy transformers, link ERP to insulin resistance, psychiatric disorders, and healing, and explore health as a dynamic field-like state optimized by flux modulation.

About the guest: Nirosha Murugan, PhD is a biophysicist studying how physical signals pattern biology to decode and reprogram health; Martin Picard, PhD is a mitochondrial psychobiologist at Columbia University, exploring how mitochondrial energy dynamics connect to human experiences, health, and healing. They collaborate on biophotons, light emission, and multi-scale energy signaling.

Discussion Points:

• Mitochondria transform electrons from food into versatile electricity via proton gradients.
• Energy Resistance Principle: transformation needs resistance; chronic high resistance causes dissipative heat, damage, aging.
• GDF15 cytokine signals mitochondrial stress to brain, triggering energy conservation/mobilization.
• Insulin resistance: adaptive defense against electron overload, reversible by fasting/exercise.
• Psychiatric illness: excess brain energy resistance; exercise, keto, psychedelics redistribute flux.
• Health: dynamic optimization of energy resistance, not absence of disease.
• Healing: daily recovery from micro-damage via balanced resistance.
• Future: energy-based diagnostics/therapies (light, TMS) over molecule-only drugs.

*Not medical advice.

Reference Paper: The energy resistance principle

Related Episode:

• M&M 70: Mitochondria, Aging, Cellular Energy, Metabolism, Gray Hair Reversal & Brain-Body Communication | Martin Picard

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How artificial light impacts female menstrual cycles and their relationship to lunar cycles of the moon.

Summary: Dr. Förster talks about how biological clocks, including circadian, tidal, lunar, and annual cycles, regulate behaviors in various species, with a focus on lunar cycle effects on human menstrual cycles. They explore historical and modern data suggesting that menstrual cycles may synchronize with lunar phases, a phenomenon potentially disrupted by modern artificial lighting, particularly blue light from LEDs post-2010. The conversation also covers circadian rhythm mechanisms in fruit flies and humans, highlighting the role of light and neuropeptides in maintaining biological synchrony.

About guest: Charlotte Förster, PhD is a senior professor at the University of Würzburg specializing in chronobiology, particularly circadian rhythms in fruit flies, and has recently explored lunar cycle influences on human menstrual cycles.

Discussion Points:

• Biological Clocks: Various clocks (circadian, tidal, lunar, annual) regulate behaviors; circadian clocks manage 24-hour cycles, while lunar clocks influence reproduction in marine species like corals and Christmas Island crabs.
• Lunar Cycle & Menstruation: Historical data (pre-2010) showed many women’s menstrual cycles synchronized with lunar phases (full or new moon), but this decreased post-2010, possibly due to blue light from LEDs disrupting biological rhythms.
• Blue Light Impact: Blue light from modern devices mimics daylight, potentially desynchronizing circadian and lunar clocks, with melanopsin in the eyes playing a key role in light sensitivity.
• Winter Synchronization: Menstrual cycle synchrony with lunar phases is stronger in winter, particularly January, possibly due to brighter moonlight or gravitational effects when Earth is closest to the Sun.
• Circadian Mechanisms: In fruit flies, 240 neurons manage circadian rhythms via clock genes with a 24-hour feedback loop, conserved in humans, where neuropeptides regulate slower, sustained rhythms.
• Health Implications: Disrupted circadian rhythms can desynchronize body clocks, impacting digestion, immunity, and increasing risks of cardiovascular issues, obesity, and cancer.
• Lifestyle Tips: To maintain synchrony, maximize daytime light exposure, minimize nighttime blue light, time meals appropriately, and exercise during the day, not late at night.

Reference paper:

• Study: Synchronization of women’s menstruation with the Moon has

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The genetic & developmental changes behind bipedalism & human anatomy.

Wide release date: October 15, 2025.

Episode Summary: Dr. Terence Capellini talks about the evolution of bipedalism in humans, exploring when and why it emerged, the anatomical changes required, and the genetic mechanisms behind these adaptations. They discuss how environmental shifts, like shrinking forests, drove the need for upright walking, the gradual skeletal changes in the pelvis and limbs, and how these changes may have facilitated larger brain sizes. Capellini highlights the complexity of evolutionary processes, emphasizing the role of multiple genetic changes in regulatory regions rather than single genes.

About the guest: Terence Capellini, PhD is a professor and chair of the Department of Human Evolutionary Biology at Harvard University. His research focuses on developmental genetics and human evolution.

Discussion Points:

• Bipedalism likely became common ~3.5 million years ago with Australopithecus afarensis, with earlier hominins like Ardipithecus showing mosaic traits.
• Environmental changes, such as shrinking forests and expanding grasslands, created selective pressures favoring bipedal locomotion.
• The human pelvis evolved to be shorter, wider, and curved, with muscles like the gluteus medius shifting to stabilize upright walking.
• Genetic changes in non-coding regulatory regions, not protein-coding genes, drive the developmental shifts in pelvic growth, with hundreds of small-effect changes involved.
• Bipedalism may have widened the birth canal, potentially enabling the evolution of larger brains in later hominins like Homo erectus.
• Humans have more slow-twitch muscle fibers than chimpanzees, supporting endurance activities like long-distance running, possibly linked to energetic trade-offs with brain growth.
• Shoulder and arm adaptations for throwing and tool use evolved more gradually, becoming prominent ~2 million years ago with Homo erectus.

Reference paper:

• Study: The evolution of hominin bipedalism in two steps

Related content:

• M&M 171: Comparative Brain Evolution: Mammals, Primates & Humans | Robert Barton

*Not medical advice.

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The biological roots of sleep are tied to mitochondrial metabolism.

Episode Summary: Dr. Gero Miesenböck discusses the evolutionary and metabolic basis of sleep, exploring how mitochondrial energy production in neurons, particularly in fruit flies, drives the need for sleep to manage harmful byproducts like reactive oxygen species and lipid peroxides. They discuss how sleep-inducing neurons sense these byproducts, the role of mitochondrial dynamics, and the broader implications for why all animals, from jellyfish to humans, require sleep. The conversation also touches on how body size and metabolism influence sleep needs across species.

About the guest: Gero Miesenböck, MD is a professor of physiology at the University of Oxford, renowned for his pioneering work in optogenetics and his research on the neurobiology of sleep using fruit flies and mice.

Discussion Points:

• Sleep is universal across animals, even in jellyfish without centralized brains, suggesting a fundamental metabolic purpose tied to mitochondrial energy production.
• Mitochondria produce energy efficiently using oxygen but generate reactive oxygen species that can damage cells through lipid peroxidation, necessitating sleep to repair this damage.
• Sleep-inducing neurons in fruit flies contain sensors that track lipid peroxidation products, acting like a digital memory to signal when sleep is needed.
• Smaller animals with faster metabolisms, like mice, require more sleep and have shorter lifespans due to higher oxygen consumption and oxidative stress.
• Mitochondrial diseases in humans often cause intense tiredness, likely due to increased electron leaks in the mitochondrial energy production process.
• The evolutionary origin of sleep likely stems from the oxygen revolution 2.5 billion years ago, enabling complex life but requiring mechanisms like sleep to manage metabolic side effects.
• Caloric restriction reduces sleep need by lowering the production of harmful metabolic byproducts, supporting the link between metabolism and sleep.

Reference paper:

• Study: Mitochondrial origins of the pressure to sleep

Related content:

• M&M 12: Organisms, Cities, Companies & the Science of Scale | Geoffrey West

*Not medical advice.

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The surprising link between oral bacteria and heart disease.

Episode Summary: Dr. Pekka Karhunen explains the connection between oral bacteria, cholesterol, and cardiovascular disease, discussing how oxidized LDL cholesterol triggers inflammation in arteries, how bacteria from the mouth can infiltrate arterial plaques to form biofilms, and the implications for heart disease prevention through lifestyle changes like better oral hygiene.

About the guest: Pekka Karhunen, MD, PhD is a medical doctor and forensic pathologist with decades of experience, specializing in cardiovascular diseases. He has created a unique biobank of coronary arteries from over 10,000 autopsies conducted in Finland. His research focuses on the role of bacteria in atherosclerosis, particularly through studying coronary artery plaques.

Discussion Points:

• Cholesterol is essential for life, but oxidized low-density lipoprotein (LDL) cholesterol is seen as a foreign substance by the immune system, leading to chronic inflammation in coronary arteries.
• Macrophages ingest oxidized LDL, turning into dysfunctional foam cells that contribute to plaque buildup, known as atheromas, in arteries.
• Plaque rupture, potentially caused by increased pressure from cholesterol accumulation or hemorrhage within the plaque, can trigger heart attacks.
• Bacteria, especially from the mouth, can enter arterial plaques via bacteremia (e.g., from dental procedures) and form biofilms, evading immune detection.
• Biofilms in plaques, made of extracellular matrix like polysaccharides, protect bacteria and may contribute to plaque instability or calcification over time.
• Poor oral hygiene is linked to higher cardiovascular disease risk, as bacteria from dental infections can enter plaques, suggesting dental care as a preventive measure.
• Karhunen’s research found oral bacteria, like Viridans streptococci, in coronary plaques, with unpublished data also detecting gut and skin bacteria, indicating diverse bacterial involvement.

Related content:

• M&M 247: Cholesterol: Immune Benefits, Heart Health, Statins & Research Malpractice | Uffe Ravnskov

*Not medical advice.

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How nutrition and medications impact mitochondrial health.

Wide release date: October 1, 2025.

Episode Summary: Dr. Chris Masterjohn talks about the intricate relationships between nutrition, prescription drugs, and mitochondrial health, discussing how molecules like acetaminophen and SSRIs affect the body beyond their intended purposes, particularly impacting inflammation and energy metabolism. The discussion gets into the broader implications of serotonin outside the brain, the side effects of commonly used medications, and the importance of personalized nutritional strategies to optimize mitochondrial function.

About the guest: Chris Masterjohn, PhD holds a doctorate in nutritional sciences and is a co-founder of Mitome, a company focused on mitochondrial testing to optimize cellular energy production.

Discussion Points:

• Acetaminophen & Inflammation: Acetaminophen (Tylenol) may contribute to chronic low-grade inflammation by blocking both the initiation and resolution of inflammation, potentially linked to health issues like autism when used during pregnancy.
• Serotonin’s Role Beyond the Brain: Approximately 95% of serotonin is found in the gut, regulating motility, with SSRIs causing side effects like nausea due to increased extracellular serotonin.
• SSRIs & Mitochondrial Function: SSRIs disrupt serotonin uptake into cells, reducing mitochondrial melatonin production, which impairs the body’s ability to handle hypoxic stress and produce ATP efficiently.
• Statins & Mitochondrial Impact: Statins, used to lower cholesterol, inhibit the mevalonate pathway, affecting not just cholesterol but also CoQ10 and vitamin K2, crucial for mitochondrial function, potentially leading to side effects like myopathy.
• Mitochondrial Testing with Mitome: Masterjohn’s company, Mitome, uses cheek swab tests to measure mitochondrial respiratory chain activity, providing personalized dietary and lifestyle recommendations to optimize cellular energy production.
• Nutrition & Mental Health: Masterjohn shares his personal experience of severe mental health issues on a vegan diet, which improved dramatically with a nutrient-dense diet rich in organ meats, highlighting individual nutritional needs.
• Energy Metabolism’s Universal Role: Mitochondrial ATP production governs everything from daily energy levels to long-term health, with personalized testing helping identify and address specific bottlenecks.

*Not medical advice.

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Genetic & environmental factors that affect brain health, including why people age faster in outer space. (Note: technical difficulties affected the audio quality of this recording somewhat)

Episode Summary: Dr. Jacob Raber explains how apolipoproteins, particularly ApoE, influence brain health and disease risk; their role in cholesterol metabolism, Alzheimer’s disease, and responses to environmental stressors like radiation and viral infections; interplay between genetics, diet, and lifestyle factors, highlighting how these affect cognitive function and resilience to stress; research into space radiation, the gut-brain axis, and potential interventions for neurodegenerative diseases.

About the guest: Jacob Raber, PhD, is a neuroscientist at Oregon Health & Science University (OHSU) in Portland, where he leads a lab studying genetic and environmental influences on brain health, particularly using mouse models with human genes.

Discussion Points:

• Apolipoproteins (ApoE2, E3, E4) are proteins involved in cholesterol and lipid metabolism in the brain, with ApoE4 increasing risks for Alzheimer’s and cardiovascular disease.
• ApoE4 carriers may face higher risks for cognitive decline but could have advantages in specific contexts, like fertility or certain infections.
• Environmental stressors, such as space radiation and viral infections like West Nile, can exacerbate oxidative stress, impacting brain health.
• The gut microbiome influences brain function indirectly via the gut-liver-brain axis, with ongoing studies exploring its role in Alzheimer’s and traumatic brain injury.
• Lifestyle factors like diet, exercise, and sleep are critical for brain health, potentially mitigating genetic risks like ApoE4.
• Statins, commonly used for cholesterol management, may impair learning in healthy animals, suggesting context-dependent effects.
• Research into space radiation reveals potential therapeutic applications, such as using heavy ion radiation for cancer treatment.
• Genetic variations, including ethnicity and sex, influence ApoE-related disease risks, with women and certain populations showing higher Alzheimer’s susceptibility.
• Chronic low-level stressors, like air pollution, may pose greater risks to brain health than acute exposures due to insufficient activation of protective mechanisms.

Related content:

• M&M 165: PUFAs in Brain Health & Disease, Dietary Fats, Brain Lipids, Nutrition | Richard Bazinet

*Not medical advice

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How maternal obesity epigenetically reprograms liver metabolism in offspring, predisposing them to metabolic disease.

Episode Summary: Dr. Elvira Mass talks about macrophages, specialized immune cells that vary by tissue and play crucial roles beyond fighting infections, such as supporting organ function; Kupffer cells (liver macrophages) and how maternal obesity during pregnancy reprograms these cells in offspring, leading to fatty liver disease, fibrosis, and even cancer later in life, based on mouse studies showing epigenetic and metabolic shifts like increased glycolysis, with insights into developmental windows, nutritional mismatches, and broader implications for human health.

About the guest: Elvira Mass, PhD, is a Professor of Developmental Immunology at the University of Bonn in Germany, where her lab focuses on the development and function of macrophages in various tissues.

Discussion Points:

• Macrophages are diverse, tissue-specific cells that develop from embryonic precursors, performing unique tasks like providing growth factors in organs.
• Kupffer cells in the liver monitor blood from the gut and are exposed to maternal nutrients during fetal development.
• Maternal obesity (induced in mice via high-fat diets) programs offspring Kupffer cells epigenetically, leading to fatty liver in newborns and progression to diseases like cancer, even on normal diets.
• A "nutritional mismatch" between in utero high-fat exposure and postnatal normal diets worsens liver issues, as cells are "prepared" for excess high-fat intake but face scarcity.
• Key mechanism: Reprogrammed Kupffer cells overproduce apolipoproteins, driving excess lipid uptake in liver cells (hepatocytes), linked to transcription factor HIF-1α and a shift to inefficient glycolysis.
• Offspring from obese mothers show sex differences (males affected earlier) and persistent changes.
• Human parallels: Rising childhood fatty liver (once rare and tied to alcoholism) correlates with maternal obesity; studies like Dutch Hunger Winter show early gestational disruptions cause lifelong issues.
• Broader factors: Microbiome changes, specific fatty acids, and environmental toxins like microplastics may also reprogram macrophages; diets in studies vary beyond fat content, affecting results.
• Advice: Maintain consistent healthy habits pre- and during pregnancy; avoid sudden diet shifts, as developmental windows are critical for long-lived cells like Kupffer cells.

Reference Paper:

• Study: Kupffer cell programming by

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Aging, tissue repair, and the longevity benefits of psilocin.

Episode Summary: Dr. Louise Hecker discusses her research on tissue repair and regeneration, explaining how fibroblasts drive wound healing by forming scar tissue but fail to resolve properly with age, leading to fibrotic diseases like pulmonary fibrosis and liver cirrhosis; they discuss aging hallmarks such as oxidative stress and telomere shortening, and highlight Hecker's study showing psilocybin's active metabolite, psilocin, extends cellular lifespan in lab cultures by reducing oxidants and preserving telomeres, while monthly doses in aged mice improved appearance and survival rates.

About the guest: Louise Hecker, PhD is an Associate Professor of Medicine at Baylor College of Medicine, specializing in repair and regeneration processes, particularly in aging and fibrotic diseases.

Discussion Points:

• Fibroblasts are dormant cells that activate during injury to pull wounds closed and form scars, then de-differentiate or die; aging impairs this, causing persistent scarring and disease.
• Aging reduces the body's regenerative capacity; different organs vary in repair efficiency, with skin healing better than heart tissue.
• Oxidative stress, like "rust" in the body, accumulates with age due to imbalanced reactive oxygen species production and antioxidant defenses, contributing to cellular damage.
• Telomeres act as protective DNA caps that shorten with cell divisions, serving as a hallmark of biological aging; sirtuins are master regulators influencing aging processes.
• Hecker's in vitro study showed psilocin dose-dependently extended fibroblast lifespan by 29-50%, lowering oxidative stress below young cell levels and preserving telomeres.
• In aged mice (equivalent to 60-65 human years), monthly high-dose psilocybin (15 mg/kg) led to healthier appearance, regrown fur, and 80% survival when controls reached 50% mortality after 10 months.
• Psilocybin's effects may stem from serotonin receptors expressed in many cell types beyond the brain, suggesting broader anti-aging potential; future work explores mechanisms, optimal dosing, and applications for age-related diseases.
• Fungi like magic mushrooms represent an under-explored "kingdom" for medicine, with psilocybin's durable effects hinting at systemic impacts on aging.

Reference Paper:

• Study: Psilocybin treatment extends cellular lifespan and improves survival of aged mice

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The effects of protein restriction on metabolism, liver hormones, brain, and behavior.

Episode Summary: Dr. Christopher Morrison talks about how animals sense and prioritize nutrients like protein, discussing defense mechanisms for essentials such as oxygen, water, sodium, and energy; the brain's role in detecting protein deprivation via signals like FGF21; trade-offs between growth, reproduction, and longevity under protein restriction; and reconciling high-protein diets for satiety and muscle maintenance with low-protein benefits for metabolic health and lifespan extension.

About the guest: Christopher Morrison, PhD is a professor and researcher at the Pennington Biomedical Research Center in Baton Rouge, Louisiana, where he has worked for over 22 years focusing on nutrition, metabolism, and chronic diseases like obesity and diabetes.

Discussion Points:

• The body prioritizes nutrients hierarchically: oxygen and water first, then sodium, energy, and protein, with weaker defenses for carbs or fats.
• Animals develop specific appetites for deprived nutrients, like salt or protein, often through post-ingestive learning rather than just taste.
• Protein restriction (e.g., 5% vs. 20% in diets) increases food intake and energy expenditure in mice to maintain protein levels, even at the cost of extra calories.
• FGF21, a liver hormone, signals protein deprivation to the brain (via NTS region), driving protein-seeking behavior and metabolic changes; it's essential for low-protein responses.
• Protein restriction extends lifespan in lab animals by suppressing growth signals like IGF-1 and mTOR, but may impair immunity or wound healing in real-world conditions.
• High protein aids satiety, weight loss, and muscle building, but overconsumption may shorten lifespan; optimal intake depends on age, activity, and goals (e.g., not for pregnant or elderly).
• No one-size-fits-all for protein: mild restriction may benefit middle-aged sedentary people for health, while athletes need more; balance avoids excesses.

Related content:

• M&M 106: Diet, Macronutrients, Micronutrients, Taste, Whole vs. Processed Food, Obesity & Weight Loss, Comparative Biology of Feeding Behavior | Stephen Simpson & David Raubenheimer

*Not medical advice.

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Cellular clean up by immune cells and how early-life fructose exposure leads to neurodevelopmental problems.

Episode Summary: Dr. Justin Perry talks about the body's constant cellular turnover—about 3 million cells die per second in adults (double in children and women)—handled by phagocytes like macrophages that engulf and digest debris to prevent diseases like lupus. They explore phagocytosis steps, macrophage adaptations in tissues like the brain (microglia), and how high fructose intake impairs microglial function in developing mice, leading to uncleared brain cells and anxiety-like behaviors, with implications for human neurodevelopmental disorders amid rising fructose consumption.

About the guest: Justin Perry, PhD is an immunologist and clinical psychologist who leads a lab at Memorial Sloan Kettering Cancer Center focusing on how the body clears dead cells and debris to maintain homeostasis.

Discussion Points:

• The body turns over 1-2% of its 30 trillion cells daily, mostly blood cells, but neurons in kids and endometrium in women turnover at ~2x this rate
• Phagocytosis involves "find me," "eat me," and digestion signals; failures can cause autoimmunity.
• Microglia are brain macrophages that uptake fructose via GLUT5 transporter.
• Early high fructose exposure (comparable to one soda daily) impairs the pruning of synapses and dead neurons.
• In mice, prenatal or postnatal fructose causes phagocytosis deficits in the prefrontal cortex, leading to heightened fear responses and poor fear extinction, mimicking anxiety disorders.
• Fructose correlates with rising neurodevelopmental issues like autism and anxiety; it's passed via breast milk, and liquid forms (e.g., sodas) overwhelm metabolic shields more than solid fruits.
• Macrophages may hold keys to diseases from atherosclerosis to cancer; deleting GLUT5 in microglia reverses fructose's effects, hinting at evolutionary roles in aging or low-oxygen states.

Related content:

• M&M 215: Cancer Metabolism: Sugar, Fructose, Lipids & Fasting | Gary Patti
• Article | Dietary Fructose & Metabolic Health: An Evolutionary Perspective

Reference Paper:

• Study | Early life high fructose impairs microglial phagocytosis and neurodevelopment

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The potential link between acetaminophen (Tylenol) and autism, with a surprise phone call from RFK partway through.

Episode Summary: Dr. William Parker talks about autism spectrum disorder (ASD), its rising prevalence since the 1980s, and the controversial hypothesis that acetaminophen exposure in susceptible infants and children triggers most cases via oxidative stress. They discuss ASD's clinical definition; historical misconceptions like the "refrigerator mother" theory; genetic susceptibilities; acetaminophen's metabolism, which produces toxic byproducts in underdeveloped livers, leading to brain effects.

About the guest: William Parker, PhD spent nearly 30 years as a professor at Duke University researching underlying causes of chronic conditions, including discovering the immune function of the human appendix and pioneering studies on immune systems in wild animals.

Discussion Points:

• Autism is a spectrum disorder with core symptoms like social deficits, repetitive behaviors, and aversion to new stimuli.
• Parker argues overwhelming evidence points to acetaminophen as the primary trigger in susceptible individuals, causing oxidative stress via toxic metabolite NAPQI.
• Acetaminophen, marketed as Tylenol or paracetamol, was not tested for neurodevelopmental effects in neonatal animals until 2014, despite widespread use since 1886; it's metabolized differently in babies, whose livers lack mature detox pathways.
• Susceptibility factors include low glutathione (an antioxidant), poor sulfation/glucuronidation metabolism, folate receptor autoantibodies, and events like immune reactions that prompt acetaminophen use during oxidative stress.
• Regressive autism, where children lose milestones after seeming normal, often follows acetaminophen given for fevers or illnesses, explaining parental vaccine suspicions (as shots coincide with drug use).
• Adult acetaminophen is generally safe but causes liver toxicity in overdoses or with alcohol; antidote is NAC to boost glutathione.
• Parker has suggested to policymakers that we should avoid acetaminophen during pregnancy, birth, and early childhood (under age 3-5); parents should plan ahead for fevers/pain without it, but seek medical help for unusual symptoms.

*Not medical advice.

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Wide release date: August 25, 2025

Episode Summary: Dr. Uffe Ravnskov talks about his decades-long career challenging the idea that high cholesterol causes heart disease, discussing LDL's protective role in the immune system by binding to bacteria, the harms and biases in statin research influenced by pharmaceutical companies, evidence that high cholesterol benefits the elderly and reduces infection/cancer risks, and how mental stress or infections elevate cholesterol as a response rather than a cause.

About the guest: Uffe Ravnskov, MD, PhD is a physician and independent researcher who earned his MD from the University of Copenhagen in 1961 and a PhD in nephrology. He has worked in various clinics in Sweden since the 1960s, focusing his research on challenging the cholesterol hypothesis in heart disease. Now 91, he has published over 200 papers, authored books like "The Cholesterol Myths.”

Discussion Points:

• LDL cholesterol helps the immune system by sticking to bacteria, clumping them for removal; low LDL increases infection risk.
• Animal studies show injecting LDL protects against lethal infections, while historical data links severe infections to worse atherosclerosis.
• Elderly people with high cholesterol live longer; low cholesterol raises mortality risk more than high levels.
• Familial hypercholesterolemia (FH) doesn't cause early death via cholesterol alone—co-inherited coagulation factors are the issue, and FH patients often have lower infection rates.
• Statins lower LDL but increase infection risk, cause muscle weakness/brain issues (often blamed on aging), and show no clear benefit in unbiased meta-analyses.
• Research biases include cherry-picking studies, exaggerating benefits via relative (not absolute) risk, and pharma funding suppressing critical views.
• Mental stress can raise cholesterol by 10-50% in 30 minutes, often misread as a heart disease cause rather than an effect.
• Saturated fat and high cholesterol aren't proven harmful; Ancel Keys' claims ignored contradictory evidence.
• Stopping statins often reverses side effects quickly, improving quality of life.

Related episode:

• M&M 244: Seed Oils & Heart Disease: Oxidized LDL, Cholesterol, Fat & Cardiology | Tucker Goodrich

Reference Paper:

• LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature

*Not medical advice.

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The appendix's hidden role and how "good" parasites like helminths shape immune health.

Episode Summary: Dr. William Parker discusses gut anatomy, the appendix's role in harboring beneficial bacterial biofilms and immune tissue, and how modern hygiene depletes helminths (intestinal worms), causing immune overreactions like allergies, autoimmunity, and psychiatric conditions. He explores helminth self-therapy for treating relapsing MS, depression, and allergies; challenges in clinical trials due to patent issues; and why COVID-19 was milder in low-income, helminth-rich regions.

About the guest: William Parker, PhD conducted research at Duke University for over 27 years on immunology, appendicitis, and the hygiene hypothesis. After retiring from Duke, he serves as a visiting scholar at the University of North Carolina at Chapel Hill, leading efforts on biome reconstitution via helminths.

Discussion Points:

• Appendix is not vestigial; it concentrates immune tissue and biofilms to cultivate good gut bacteria, preventing pathogens via mucus and IgA antibodies.
• Hygiene hypothesis: Soap, toilets, and clean water reduce helminths/protozoa, leading to untrained, hyperactive immunity and rising allergies/autoimmunity since the 1800s.
• Helminths (worms) stimulate immune "exercise," training immunity; biohackers use hookworms (cheap, skin-entry), porcine whipworms, or rat tapeworms orally for relief from allergies, MS flares, depression/anxiety.
• Effects are temporary; need ongoing exposure (e.g., replenish every 6 months); immigrants from helminth-rich areas develop Western diseases within a few years.
• COVID-19: Hyper-immunity caused severe reactions in hygienic West, but helminth presence in low-income Africa/Asia prevented cytokine storms, leading to empty clinics.
• Therapy barriers: Non-patentable organisms require $100M+ trials; push for open-source, government-funded biome restoration over crude immunosuppressants.

Related episode:

• M&M 144: Inflammation, Innate Immunity, Allergies & Allergens, Immune System Evolution, Fasting & Metabolism | Clare Bryant

*Not medical advice.

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What is the core evolved function of the endocannabinoid system?

Episode Summary: Dr. Giovanni Marsicano is a neuroscientist based in Bordeaux, France, where he leads a research group at INSERM focusing on the endocannabinoid system.

About the guest: Giovanni Marsicano, PhD discusses the endocannabinoid system, starting with its core components like CB1 receptors and lipid-based molecules derived from omega-6 fatty acids; its cellular signaling, evolutionary role in energy storage for uncertain futures (exostasis vs. homeostasis); effects across tissues; motivation, appetite, pain relief, and anxiety regulation; biphasic effects of cannabinoids.

Discussion Points:

• The endocannabinoid system acts as an "exostatic" regulator, promoting energy accumulation for future needs by enhancing food palatability, nutrient absorption, and fat storage, unlike "endostatic" systems that address immediate hunger.
• CB1 receptors appear in vertebrates with adipose tissue, suggesting an evolutionary link to storing fat for survival in unstable environments.
• Endocannabinoids are lipids from omega-6 fats; high intake boosts their levels, potentially fueling obesity by creating a self-perpetuating cycle of overeating.
• Activation of CB1 can have biphasic effects due to receptors on different cell types like excitatory vs. inhibitory neurons.
• Pregnenolone, a steroid precursor, acts as a natural CB1 inhibitor to prevent excessive activation, blocking harmful effects like psychosis from high THC doses.
• The system influences motivation beyond food, including sex and even human activities like sports or storytelling, by rewarding actions for potential future benefits.
• In the brain, CB1 on mitochondria and astrocytes modulates energy use, olfaction, and social stress transmission, with implications for disorders like Alzheimer's.

Reference Paper:

• CB1 Receptor as the Cornerstone of Exostasis

Related episode:

• M&M 123: Endocannabinoids, Stress, Anxiety, Cannabis | Matthew Hill

*Not medical advice.

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Overview and alternative interpretation to the mainstream view on how dietary fat and cholesterol relate to cardiovascular disease.

Episode Summary: Tucker Goodrich is an engineer by training who has become a prominent independent researcher and blogger on nutrition and metabolic health, focusing on the harms of seed oils and polyunsaturated fats.

About the guest: Nick Jikomes and Tucker Goodrich explore atherosclerosis and heart disease, critiquing the standard model that blames high LDL cholesterol while highlighting how oxidized LDL—driven by dietary linoleic acid from seed oils—plays a key role in plaque formation and inflammation; they discuss historical shifts in heart disease rates, genetic factors like familial hypercholesterolemia, the limitations of animal studies, and why reducing seed oil intake could prevent issues more effectively than just lowering cholesterol.

Discussion Points:

• Atherosclerosis involves plaque buildup in arteries, often leading to heart attacks, but plaques contain oxidized fats and cholesterol, not just native cholesterol.
• Dietary cholesterol has little impact on blood levels or heart disease in humans, unlike in rabbits used in many studies.
• High LDL may not be inherently bad; oxidized LDL from polyunsaturated fatty acids (PUFAs) like linoleic acid causes macrophages to overeat and form harmful foam cells.
• Familial hypercholesterolemia patients only show higher heart disease rates in modern, industrial diets high in seed oils, not historically.
• Populations like the Kitavans and Tsimané have high apoB but no heart disease on traditional diets low in industrial foods.
• Fried foods are oxidized seed oils, explaining why they're unhealthy despite omega-6 fats being labeled "heart-healthy."
• Omega-3 fats can displace omega-6 in cells, reducing oxidation risk.

Reference Papers:

• Witztum & Steinberg (1991)
• Boren et al. (2022)

Related episode:

• M&M 136: Seed Oils, Omega-6 PUFAs, Inflammation, Obesity, Diabetes, Chronic Disease & Metabolic Dysfunction | Chris Knobbe

*Not medical advice.

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Human metabolism, primate evolution, and modern health challenges with evolutionary anthropologist Herman Pontzer.

Episode Summary: Anthropologist Dr. Herman Pontzer discusses human evolution and metabolism, comparing humans to primates like chimps and gorillas to explain our higher energy use, bigger brains, and longer lives despite trade-offs in reproduction and activity; they discuss dietary shifts from plant-based to hunting-gathering, metabolic adaptations, and modern issues like obesity, where exercise aids health but diet drives weight loss, emphasizing ultra-processed foods' role in overeating and the promise of new drugs like GLP-1 agonists.

About the guest: Herman Pontzer, PhD is a professor of evolutionary anthropology and global health at Duke University. He is the author of books like "Burn" and "Adaptable," which explore how bodies adapt to diets, activity, and environments.

Discussion Points:

• Humans burn 20% more daily energy than other primates (controlling for body size), enabling big brains, more babies, and longer lives, but requiring efficient food strategies like hunting and gathering.
• Unlike apes, humans evolved smaller guts, higher body fat (15-30% vs. apes' <10%), and mixed diets of animal and plant foods.
• Hunter-gatherers like the Hadza are far more active than sedentary Westerners but burn similar calories, as bodies adapt by reducing basal metabolism, inflammation, and hormones.
• Obesity stems more from increased calorie intake via ultra-processed foods than it does from reduced activity; exercise boosts health but rarely causes major weight loss on its own.
• Early humans likely scavenged rancid meat, evidenced by low stomach pH similar to vultures, aiding digestion of risky foods.
• Ketosis isn't unique to high-meat diets; even Inuit on low-carb diets resist it, and other carnivores don't stay in ketosis constantly.
• Across global populations, richer countries have higher BMI and slightly higher total energy expenditure due to larger bodies, but basal rates drop with lower pathogen loads.
• For weight loss, Dr. Pontzer points to diets high in fiber/protein for satiety; intermittent fasting works by cutting calories, not magic; GLP-1 drugs mimic hormones to curb hunger, although we stay mindful of potential long-term effects.

Related episode:

• M&M 160: Diet, Hunting, Culture and Evolution of Paleolithic Humans & Hunter Gatherers | Eugene Morin

*Not medical advice.

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The deep connection between sunlight and life, from the scale of the cosmos to the quantum.

Episode Summary: Astrophysicist Dr. Robert Fosbury discusses the sun's characteristics as a star, its analogies to living systems via entropy and complexity, and Erwin Schrödinger's insights on life as order-maintaining entities; he explores how near-infrared (NIR) light from the sun penetrates bodies to enhance mitochondrial function and metabolism, critiques modern artificial lighting's health impacts like mitochondrial dysfunction leading to diseases, and advocates returning to natural light environments for better wellness, drawing connections from cosmology to everyday architecture and lifestyle.

About the guest: Robert Fosbury, PhD is a is a retired astrophysicist. He spent his career at the European Space Agency, working on Hubble and JWST projects, and now pursues interdisciplinary research linking stellar phenomena to biological processes like light's impact on vision and metabolism.

Discussion Points:

• Stars like the sun maintain low-entropy states by exporting entropy as light, mirroring how life ingests low-entropy food to sustain order and homeostasis.
• The universe's complexity peaks midway in entropy increase, with stars producing elements that enable biological complexity, evolving toward cognition.
• Near-infrared light, peaking in solar output at ~1.6 microns due to atmospheric physics, catalyzes mitochondrial ATP production by facilitating electron transport, not via photosynthesis but photo-metabolism.
• Modern LEDs and windows block near-infrared, contributing to mitochondrial dysfunction, obesity, diabetes, and aging; historical thermal lights like incandescents provided beneficial infrared.
• Outdoor environments, especially under trees, flood bodies with reflected near-infrared for health, while blue skies act as cold sinks boosting thermodynamic efficiency.
• Eyes are mitochondria-rich, vulnerable to poor light; therapies using near-infrared slow macular degeneration by improving energy production.
• Ultra-processed foods are "high-entropy" with no structural order, akin to waste, reducing nutritional value for maintaining bodily order.
• Practical fixes: Use low-voltage incandescents indoors, prioritize outdoor time, design buildings with infrared-transmitting glass, and light people, not spaces, for energy savings and health.

Related episode:

• M&M 146: Photobiology, Sunlight, Firelight, Incandescent Bulbs vs.

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How brain synapses work and fuel themselves with fat.

Episode Summary: Dr. Timothy Ryan talks about the high energy costs of synapses, the role of mitochondria and glycolysis, and challenge the long-held view that the brain relies solely on glucose by discussing new evidence that neurons burn fats from lipid droplets for fuel, especially during activity. The talk touches on metabolic flexibility, links to epilepsy treatments like ketogenic diets, neurodegenerative diseases, and future research on brain energy sources.

About the guest: Timothy Ryan, PhD is a professor of biochemistry at Cornell University. His research focuses on the molecular mechanisms of synaptic transmission, particularly vesicle recycling and the bioenergetics that power neural communication.

Discussion Points:

• Synapses are tiny structures with ~100 vesicles per site (on average), converting electrical signals to chemical ones.
• Brain tissue is energy-hungry due to trillions of synapses (in humans), relying on local mitochondria (present in only ~half of synapses) and glycolysis.
• Vesicles use proton pumps and transporters to concentrate neurotransmitters, requiring ATP to maintain gradients.
• Neurons are metabolically fragile; cutting fuel supply quickly impairs synapses.
• Dogma held brains don't burn fats, but new work shows neurons form lipid droplets (fat stores) that are invisible because constantly used for energy via beta-oxidation.
• Silencing neurons builds lipid droplets like resting muscle; activity speeds their breakdown, indicating demand-driven fat use.
• Inhibiting neuron-specific fat-processing enzymes accumulates droplets and induces torpor (hibernation-like state) in animals, signaling metabolic stress.
• Ketogenic diets aid epilepsy by shifting to ketones; fats may explain this, with potential ties to aging and neurodegeneration like Alzheimer's.
• Brain may be a "hybrid" fuel user (glucose + fats), with open questions on fat sources and roles in cognition or disease protection.

Related episode:

• M&M 158: Ketosis & Ketogenic Diet: Brain & Mental Health, Metabolism, Diet & Exercise, Cancer, Diabetes | Dominic D'Agostino

*Not medical advice.

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Episode Summary: Dr. Eugene Chang talks about the microbiome’s role as a vital organ, the impacts of antibiotics and Western diets on microbial health, and strategies for restoring a damaged microbiome through diet and fecal microbial transplants. They delve into microbiome dysbiosis, its links to modern diseases, and Chang’s research on personalized microbiome interventions.

About the guest: Eugene Chang, MD is a physician-scientist and Professor of Medicine at the University of Chicago, specializing in gastroenterology. His research focuses on the gut microbiome as a vital organ influencing metabolic and immune health.

Discussion Points:

• The gut microbiome is a vital organ, acquired early in life, that supports metabolic and immune functions, but can be disrupted by antibiotics, leading to diseases like C. difficile colitis.
• Western diets, high in saturated fats and low in fiber, contribute to microbiome dysbiosis, linked to modern conditions like inflammatory bowel diseases, obesity, and allergies.
• Microbiome health is better assessed by functional markers (e.g., short-chain fatty acid production) than taxonomic diversity, as diversity varies widely among healthy individuals.
• A patient with severe food intolerance due to antibiotic-induced microbiome damage was treated over 50 weeks with a tailored diet, restoring healthy microbiome function.
• Different dietary fibers (e.g., beans vs. seaweed) are metabolized at varying rates, affecting gut health; fermented foods like kefir can bypass digestion issues.
• Diet can rapidly reshape the microbiome within 24-48 hours, but severe dysbiosis may require microbial transplants if key microbes are extinct.
• Chang’s research shows a high-fiber, low-fat diet outperforms fecal microbial transplants in restoring microbiome resilience in mice post-antibiotics.
• Future microbiome medicine may involve personalized “omni microbial transplants” targeting both small and large intestines for comprehensive restoration.

Related episode:

• M&M 203: Metagenomics, Microbiome Transmission, Gut Microbiome in Health & Disease | Nicola Segata

*Not medical advice.

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The genetics of sleep duration and sleep timing.

Episode Summary: Dr. Ying-Hui Fu discusses her research on the genetics of sleep, focusing on natural short sleepers who thrive on 4-6 hours of sleep and the heritability of sleep traits like duration and timing. She explores how sleep efficiency, rather than just duration, may explain why some need less sleep without health deficits, and delves into the molecular and circadian mechanisms regulating sleep.

About the guest: Ying-Hui Fu, PhD is a neuroscientist and professor at UCSF, where her lab studies the genetics of human sleep behaviors, particularly sleep duration and schedule.

Discussion Points:

• Sleep Traits Are Genetic: Sleep duration (how long you sleep) and sleep schedule (when you sleep) are partially heritable, with most people needing 7-9 hours, while rare natural short sleepers thrive on 4-6 hours.
• Natural Short Sleepers: These individuals fall asleep quickly, have high sleep efficiency, and live healthy, active lives without deficits, possibly due to faster toxin clearance and repair during sleep.
• Sleep Efficiency Matters: Short sleepers may complete restorative sleep processes (e.g., clearing toxins, repairing damage) more efficiently, allowing them to need less sleep.
• Circadian & Entrainment Pathways: Sleep timing is regulated by a molecular clock and environmental cues like light, with mutations in entrainment pathways causing extreme schedules (e.g., early bedtime or night owl tendencies).
• Modern Lifestyle Harms Sleep: Stimuli like blue light and tense media disrupt sleep patterns, leading to widespread sleep deprivation and health risks.
• Shift Work Risks: Shift workers face higher risks of diseases like cancer and neurodegeneration due to disrupted sleep cycles, though genetic background influences susceptibility.
• Finding Your Sleep Rhythm: A two-week vacation without stimulants or artificial light can help determine your natural sleep schedule and duration.
• Sleep’s Health Impact: Poor sleep is a major factor in aging and diseases like Alzheimer’s, making it as critical as diet and exercise for health.

Related episode:

• M&M 237: Circadian Biology: Genetics, Behavior, Metabolism, Light, Oxygen & Melatonin | Joseph Takahashi

*Not medical advice.

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A blend of biology, philosophy, and history exploring how hormones and endocrine disruptors affect social behavior and society.

Episode Summary: Dr. Charles Cornish-Dale discusses the decline of masculinity in modern society, linking it to falling testosterone levels, environmental endocrine disruptors, and the limitations of liberal democracy. Drawing on Francis Fukuyama’s “End of History & the Last Men” and historical perspectives, Cornish-Dale argues that biological and societal factors, including diet and hormonal interventions like birth control, are reshaping male and female behaviors, with profound implications for health and social structures.

About the guest: Charles Cornish-Dale, PhD is a medieval historian and anthropologist with a PhD from Oxford. His new book is, “The Last Men: Liberalism and the Death of Masculinity.”

Discussion Points:

• Thymos & Masculinity: Cornish-Dale uses the ancient Greek concept of thymos, meaning spiritedness, to explain male drives for recognition and distinction, which he ties to testosterone-driven behaviors.
• Testosterone Decline: Studies like the Massachusetts Male Aging Study show a ~20% drop in male testosterone levels over 17 years, correlating with reduced reproductive health and social withdrawal.
• Endocrine Disruptors: Chemicals in plastics, pesticides, and soy products mimic estrogen, disrupting hormonal balance and potentially causing developmental and behavioral issues.
• Diet & Behavior: Historical shifts to grain-based diets, as noted by Plato, and modern plant-based trends may suppress thymos and alter hormonal profiles, impacting societal dynamics.
• Hormonal Contraceptives: Birth control can thin the ventromedial prefrontal cortex in women, affecting emotional regulation, especially if taken during teenage years, with potential permanent effects.
• Fukuyama’s End of History Framework: Cornish-Dale critiques liberal democracy’s inability to satisfy megalothymia (the desire to be better), contributing to a crisis of purpose for men.

Related episode:

• M&M 193: History of Diet & Food, Population Density & Social Stability, Psychological Pandemics, Physical & Mental Health in Civilizational Cycles

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How our biological clocks shape biology from the molecular to behavioral level.

Episode Summary: Dr. Joseph Takahashi discusses circadian rhythms, exploring their biological basis, from molecular mechanisms to their impact on metabolism and health; the discovery of circadian clock genes; role of the suprachiasmatic nucleus, and how light, feeding, and oxygen influence these rhythms. The conversation highlights practical implications, such as the effects of artificial light and meal timing on health, and touches on emerging research linking stronger circadian clocks to longevity.

About the guest: Joseph Takahashi, PhD is a renowned neuroscientist at UT Southwestern Medical Center, where he leads research on circadian clock genes.

Discussion Points:

• The suprachiasmatic nucleus in the hypothalamus acts as the brain's central clock, syncing with light via the retina.
• Key circadian genes like CLOCK and BMAL regulate thousands of genes, especially those involved in metabolism, impacting health outcomes.
• Internal desynchronization, when brain and organ clocks misalign (e.g., from eating at night), can lead to metabolic issues like pre-diabetes.
• In mice, eating at the right time (night for nocturnal animals) extends lifespan by up to 35% under caloric restriction, compared to 10% with spread-out feeding.
• Artificial light, especially blue light at night, disrupts melatonin and circadian rhythms, while natural sunlight supports healthy eye development.
• Melatonin, a darkness-signaling hormone, is best for resetting rhythms (e.g., jet lag) at low doses, not as a sedative, and U.S. supplements vary widely in quality.
• Oxygen-sensing proteins interact with circadian clock components, hinting at links between altitude, metabolism, and health.
• Learning and memory show diurnal variations, with better performance at certain times, influenced by circadian modulation of synaptic activity.
• A stronger circadian clock, created genetically in mice, led to 16% longer lifespan and resistance to weight gain (unpublished research).

Related episode:

• M&M 202: Why Do Animals Sleep? | Vlad Vyazovskiy

*Not medical advice.

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Cellular self-organization, cytoskeleton dynamics, and membrane wound healing.

Episode Summary: Cell Biologist Dr. Bill Bement explains the dynamic world of the cell cortex, discussing how actin filaments and microtubules drive processes like cell division and wound healing through self-assembly and self-organization; energy dynamics of these processes; the role of rho GTPases in patterning; the implications for diseases such as cancer and muscular dystrophy, using vivid analogies and video demonstrations to make complex concepts accessible.

About the guest: Bill Bement, PhD is a cell biology professor at the University of Wisconsin-Madison, where he has studied cellular processes for over 30 years. He leads a lab focused on the cell cortex, investigating cell division and repair. His work emphasizes self-organization and cytoskeletal dynamics, contributing to insights into diseases like muscular dystrophy.

Discussion Points:

• The cell cortex, the outer layer of a cell, includes the plasma membrane & underlying proteins like actin & myosin, which enable dynamic shape changes.
• Actin filaments self-assemble without energy input, growing & shrinking to facilitate cell movement and division, while microtubules, stiffer hollow tubes, aid in chromosome separation.
• Self-organization in cells, driven by energy-dependent feedback loops, creates complex patterns like mitotic spindles.
• Cellular wound healing involves concentric rings of rho GTPases and actin, closing wounds rapidly, a process critical for surviving natural damage from mechanical stress or toxins.
• Energy costs of cytoskeletal rearrangements are significant but likely less than protein synthesis, though precise measurements remain challenging.
• Cancer metastasis may rely on enhanced cell repair, allowing metastatic cells to survive mechanical damage while squeezing through tissues.
• Muscular dystrophy involves excessive damage or impaired repair, highlighting the importance of cell repair mechanisms.
• Bement’s lab is developing tools for synthetic self-organization, aiming to manipulate cellular processes to address repair deficits in diseases.

Related episode:

• M&M 220: Cell Death, Oxidative Stress, PUFAs & Antioxidants | Pamela

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How brains compute and learn, blending neuroscience with AI insights.

Episode Summary: Dr. Marius Pachitariu discusses how the brain computes information across scales, from single neurons to complex networks, using mice to study visual learning. He explains the differences between supervised and unsupervised learning, the brain’s high-dimensional processing, and how it compares to artificial neural networks like large language models. The conversation also covers experimental techniques, such as calcium imaging, and the role of reward prediction errors in learning.

About the guest: Marius Pachitariu, PhD is a group leader at the Janelia Research Campus, leading a lab focused on neuroscience with a blend of experimental and computational approaches.

Discussion Points:

• The brain operates at multiple scales, with single neurons acting as computational units and networks creating complex, high-dimensional computations.
• Pachitariu’s lab uses advanced tools like calcium imaging to record from tens of thousands of neurons simultaneously in mice.
• Unsupervised learning allows mice to form visual memories of environments without rewards, speeding up task learning later.
• Brain activity during sleep or anesthesia is highly correlated, unlike the high-dimensional, less predictable patterns during wakefulness.
• The brain expands sensory input dimensionality (e.g., from retina to visual cortex) to simplify complex computations, a principle also seen in artificial neural networks.
• Reward prediction errors, driven by dopamine, signal when expectations are violated, aiding learning by updating internal models.
• Large language models rely on self-supervised learning, predicting next words, but lack the forward-modeling reasoning humans excel at.

Related episode:

• M&M 44: Consciousness, Perception, Hallucinations, Selfhood, Neuroscience, Psychedelics & "Being You" | Anil Seth

*Not medical advice.

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How dietary fats and cannabinoids shape brain function and mental well-being.

Episode Summary: Dr. Steven Laviolette discusses the role of lipids, particularly endocannabinoids and fatty acids, in brain signaling and mental health, discussing how dietary omega-3 and omega-6 imbalances, prenatal THC exposure, and fatty acid binding proteins (FABPs) impact mood, anxiety, and neuroinflammation, while highlighting potential dietary interventions to mitigate these effects.

About the guest: Steven Laviolette, PhD is a professor at the University of Western Ontario, holding a PhD, and his lab focuses on the brain’s cannabinoid system and its role in mental health. He investigates how cannabinoids and fatty acids influence brain development and disorders like anxiety and schizophrenia.

Discussion Points:

• The brain uses fats like endocannabinoids (e.g., anandamide, 2-AG) not just for structure but as signaling molecules to regulate emotional and cognitive processing.
• Prenatal THC exposure in rodents skews the omega-3/omega-6 balance toward pro-inflammatory omega-6, leading to cognitive and mood issues in offspring, but omega-3 supplementation can mitigate these effects.
• Fatty acid binding proteins (FABPs), especially FABP5, shuttle endocannabinoids like anandamide to degradation sites, and inhibiting FABP5 increases anandamide levels, reducing anxiety and depression without addictive side effects.
• FABP5 inhibitors show promise as safer alternatives to benzodiazepines.
• Both THC and CBD can induce problems during early development, challenging the notion that CBD is universally safe, especially during pregnancy.
• Dietary interventions, like omega-3 supplementation or antioxidants (e.g., L-theanine, N-acetylcysteine), may counteract the negative psychiatric effects of cannabinoid exposure, particularly during adolescence.
• The North American diet, high in omega-6, contributes to neuroinflammation and mental health issues, underscoring the need for nutritional neuroscience to address these imbalances.

Related episode:

• M&M 165: PUFAs in Brain Health & Disease, Dietary Fats, Brain Lipids, Nutrition | Richard Bazinet

*Not medical advice.

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Are seed oils really driving chronic disease (and sunburns), or is it hype?

Episode Summary: Dr. Brian Kerley talks about the health impacts of seed oils, their high omega-6 fatty acid content, and their role in chronic diseases through mechanisms like lipid peroxidation and oxidative stress. They explore how these industrially processed oils may contribute to conditions like heart disease and obesity, discuss the challenges of studying their long-term effects, and highlight the cultural and political dimensions of dietary trends.

About the guest: Brian Kerley, MD is a family medicine-trained hospitalist physician who gained online prominence as the "Seed Oil Disrespecter" through his meme account, raising awareness about the health risks of seed oils.

Discussion Points:

• Seed Oils & Health Risks: Seed oils (e.g., soybean, corn, etc.) are high in omega-6 polyunsaturated fatty acids (PUFAs), linked to oxidative stress and lipid peroxidation, producing toxic compounds like 4-HNE and acrolein that damage cells.
• Evolutionary Perspective: The high omega-6 levels in modern diets are evolutionarily novel, deviating from natural omega-6 to omega-3 ratios found in traditional diets, potentially exacerbating health issues across diverse populations.
• Challenges with RCTs: Randomized controlled trials (RCTs) often fail to capture the long-term effects of seed oils due to the need for extended washout periods (up to 8 years) and the pervasive presence of omega-6 in modern food environments.
• Cultural & Political Coding: Dietary trends like seed oil avoidance have become politically charged, with Kerley noting the polarization between institutional health narratives and alternative health communities, complicating public health discussions.
• Personal Impact: Dr. Kerley’s focus on seed oils stems from personal experiences, including managing his daughter’s mitochondrial disorder, highlighting the personal stakes in dietary choices.

Related episode:

• M&M 192: Seed Oils, Chronic Disease, Diet & Religious Cults, Mainstream Medicine vs. Independent Research | Tucker Goodrich

*Not medical advice.

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A critique of SSRIs and pharma’s influence on medicine, including SSRI-induced sexual dysfunction, suicidality, and violence.

Long Summary: Dr. David Healy critiques modern medicine, focusing on SSRIs and psychiatric medicine, including: how pharmaceutical companies manipulate clinical trial data, ghostwrite studies, and influence medical practice, often ignoring patient experiences; highlighting issues like post-SSRI sexual dysfunction (PSSD), the immediate sensory effects of SSRIs, and their potential to induce suicidal or violent behavior; challenging the reliance on randomized controlled trials (RCTs) over individual patient reports; and more.

About the guest: David Healy, MD, PhD, a psychiatrist and pharmacologist, has decades of experience researching the serotonin system and SSRIs, working across Ireland, the UK, Canada, and the US. He is a professor at McMaster University and a vocal critic of pharmaceutical industry practices.

Discussion Points:

• SSRIs cause near-immediate sensory effects, like genital numbing, in most people.
• Post-SSRI sexual dysfunction (PSSD) can persist for years or decades after stopping the drug, affecting many long-term users.
• Healy argues RCTs prioritize averages over individual experiences, often missing serious side effects like suicidality.
• Pharmaceutical companies ghostwrite studies and manipulate data, with journals like the New England Journal of Medicine publishing misleading articles.
• Serotonin theory of depression lacks evidence.
• Industry tactics include dismissing patient reports as anecdotes and using high doses in trials to mask weak efficacy.
• SSRIs can increase suicide risk, not just during initiation but also when adjusting doses or withdrawing, as seen in cases like the Aurora movie theater shooting.
• Regulatory bodies like the FDA often fail to investigate adverse effects due to bureaucratic processes and lack of follow-up.
• Healy emphasizes doctors’ failure to prioritize patient observations, driven by industry-influenced standards of care.

Related episode:

• M&M 88: Depression, Serotonin, SSRIs, Psychiatry & Social Media | Joanna Moncrieff

*Not medical advice.

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Episode Summary: Dr. Andrew Chadeayne discusses the chemistry of psilocybin and other psychedelics, their potential therapeutic applications, and the challenges of commercializing them in a shifting biotech market. The conversation delves into the complexities of magic mushroom composition, debunking myths like "lemon tekking," and uncovers the booming, unregulated alternative products industry, including kratom and synthetic psilocybin analogs sold in vape shops.

About the guest: Andrew Chadeayne, PhD is a chemist who also holds a law degree, specializing in patent law. He is the founder and CEO of CaaMTech, a startup specializing in the development of novel psychedelic compounds. Chadeayne collaborates with academic labs to advance psychedelic science while navigating the commercial landscape.

Discussion Points:

• Psilocybin is a prodrug converted to psilocin, but magic mushrooms contain other psychoactive molecules like beta-carbolines, which may enhance effects by inhibiting degradation.
• Chadeayne’s team develops psilocin prodrugs to shorten psychedelic trips, making clinical administration more manageable without altering effects.
• The "lemon tek" myth—that lemon juice converts psilocybin to psilocin—is false; it enhances absorption by extracting compounds, not altering chemistry.
• Magic mushroom bruising indicates psilocin degradation, as oxidized psilocin forms blue, inactive dimers.
• The multi-billion dollar alternative products industry sells kratom and synthetic psilocybin analogs, often mislabeled, in vape shops, raising safety and regulatory concerns.
• Kratom’s minor alkaloid, 7-hydroxymitragynine, is ~40x more potent than morphine, with no reported overdoses but high habit-forming potential.
• Non-hallucinogenic serotonin 2A agonists, like those developed by CaaMTech’s spinout, show promise for conditions like migraines without requiring a psychedelic trip.

Related episode:

• M&M 71: Chemistry of Magic Mushrooms, DMT Analogues, Entourage Effects in Cannabis & Fungi, Novel Psychedelic Medicines, Psychedelic Startups | Andrew Chadeayne

*Not medical advice.

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Episode Summary: Dr. Michael Wheeler talks about neuroimmune interactions, exploring how the immune system and brain communicate, particularly through the blood-brain barrier and meninges; how chronic stress and inflammation can alter brain circuits, contributing to mood disorders like depression; how drugs like psilocybin and MDMA may reduce inflammation by modulating immune cells in the meninges, offering potential therapeutic benefits.

About the guest: Michael Wheeler, PhD is an Assistant Professor of Neurology at Harvard Medical School. His lab studies how immune responses influence behavior, mood disorders, and addiction.

Key Conversation Points:

• The blood-brain barrier (BBB) is not as impermeable as once thought, allowing immune signals like cytokines to influence brain function even in healthy states.
• Chronic stress can weaken the BBB, increasing inflammation and affecting mood-regulating circuits, potentially contributing to depression.
• Microglia, the brain’s resident immune cells, help maintain neural circuits by pruning synapses and regulating metabolism.
• Psychedelics like psilocybin and MDMA can reduce inflammation by prompting immune cells (monocytes) to leave the meninges, potentially via vascular effects.
• These psychedelics may act in a context-specific “window,” requiring a dysregulated tissue state to exert anti-inflammatory effects, not as broad-spectrum anti-inflammatories.
• Neuroinflammation may underlie some treatment-resistant depression cases, suggesting immunotherapy could complement traditional psychiatric treatments.
• The brain encodes peripheral immune signals, like gut inflammation, in specific circuits, which can “remember” and recreate inflammatory responses.
• Aging may naturally increase blood-brain barrier leakiness, heightening the brain's susceptibility to peripheral inflammation.
• Future research aims to explore how psychedelics influence plasticity and their potential in treating inflammation-related diseases beyond psychiatry.

Related episode:

• M&M 2: Psilocybin, LSD, Ketamine, Inflammation & Novel Psychedelic Medicines | Charles Nichols

*Not medical advice.

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Episode Summary: New research on how dietary fats, particularly omega-6 fatty acids like linoleic acid, influence triple-negative breast cancer progression by activating the mTOR pathway, a key regulator of cell growth; role of the FABP5 protein in enhancing cancer cells’ sensitivity to omega-6 fats; differences between breast cancer subtypes; broader implications of dietary balance for health.

About the guest: John Blenis, PhD is a Professor of Pharmacology at the Meyer Cancer Center at Weill Cornell Medicine. Nikos Koundouros, PhD is a postdoctoral fellow in Blenis’ lab.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.

Key Points:

• mTOR pathway acts as a cellular “brain,” sensing nutrients like amino acids, glucose, and fats to regulate growth. Its dysregulation can drive cancer.
• High dietary omega-6 fatty acids, like linoleic acid found in seed oils, can fuel triple-negative breast cancer growth by activating mTOR.
• FABP5, a lipid chaperone protein, is overexpressed in triple-negative breast cancer, making these tumors more sensitive to omega-6 fats, suggesting its potential as a therapeutic target.
• Modern diets with high omega-6 to omega-3 ratios disrupt inflammation balance, unlike historical 1:1 ratios, potentially increasing cancer risk.
• Genetic variations and cancer subtypes highlight the need for tailored dietary recommendations, as blanket nutrition advice may not suit all patients.
• While omega-6 fats exacerbate existing triple-negative breast cancer, their role in initiating cancer remains unclear, requiring further study.
• High omega-6 intake may influence other cancers (e.g., prostate, colon) and chronic diseases like obesity, linked to FABP5 and inflammation.

Related episode:

• M&M 200: Dietary Fats & Seed Oils in Inflammation, Colon Cancer & Chronic Disease | Tim Yeatman & Ganesh Halade

*Not medical advice.

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Episode Summary: Dr. Gyorgy Buzsaki discusses the hippocampus’s role beyond memory and spatial navigation, delving into its broader functions in cognition, action planning, and brain-body interactions; how hippocampal rhythms, like sharp wave ripples, influence memory consolidation, glucose regulation, and metabolic health, challenging conventional neuroscience assumptions; the interplay of brain rhythms, sleep, and preconfigured neural dynamics; the history and conceptual foundations of neuroscience; and more.

About the guest: Gyorgy Buzsaki, MD, PhD is a professor at NYU. He leads a lab investigating how neural circuits underpin cognition, particularly through oscillations and brain-body interactions. His work has significantly advanced understanding of memory formation and spatial navigation.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.

Key Conversation Points:

• Hippocampus isn’t just for memory or navigation; it may orchestrate action planning and abstract representations of the world, shaped by evolutionary constraints.
• Brain rhythms, like sharp wave ripples, synchronize neural activity, enabling efficient communication and impacting bodily functions like glucose homeostasis.
• Sharp wave ripples, prominent during non-REM sleep and consummatory states, are critical for memory consolidation and may link sleep disruptions to metabolic disorders.
• Buzsaki challenges the idea of memory as fixed synaptic patterns, proposing it’s more like dynamic, cloud-like sequences, endlessly reconfigurable.
• The brain’s intrinsic dynamics prioritize action generation and learning from consequences over external representations.

Related episode:

• M&M 16: Sleep, Dreams, Memory & the Brain | Bob Stickgold

*Not medical advice.

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The biophysics of life, exploring how light & energy shape biology, with biophysicist Dr. Nirosha Murugan.

Episode Summary: Dr. Murugan discusses the role of biophysics in biology, focusing on how light, particularly biophotons emitted by cells, influences processes like wound healing, neural activity, and cancer detection; how microtubules may act as biological fiber optics, the impact of modern light environments on health; her work inducing limb regeneration in frogs using silk hydrogels and growth factors; cancer as an energetic dysfunction; potential of non-invasive photonic diagnostics; the need for new tools to study these phenomena.

About the guest: Nirosha Murugan, PhD is a biophysicist and assistant professor at Wilfrid Laurier University in Waterloo, Ontario. Her lab investigates the biophysics of life.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.

Key Conversation Points:

• Cells emit biophotons, ultra-weak light tied to metabolism, which may carry information for processes like immune response and neural communication.
• Microtubules might function as biological fiber optics, potentially guiding light within cells for signaling purposes.
• Red and near-infrared light can accelerate wound healing and reduce inflammation, likely by modulating mitochondrial activity.
• Cancer cells emit distinct photonic signatures, which could enable non-invasive diagnostics by detecting light differences from healthy tissues.
• Modern light environments, unlike natural sunlight, may subtly affect health by altering biological responses to electromagnetic signals.
• Biological systems act as metamaterials, patterning energy flow in ways that constrain and shape molecular and behavioral outcomes.

Related episode:

• M&M 221: Regenerative Energy & the Light Inside You | Jack Kruse

*Not medical advice.

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Short Summary: Dr. Alex Kwan unpacks the latest neuroscience research on how psychedelics like ketamine & psilocybin reshape the brain.

About the guest: Alex Kwan, PhD, is an associate professor of biomedical engineering at Cornell University. His lab employs advanced imaging to study how psychedelics and other drugs affect the mammalian brain.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.

Episode Summary: Dr. Alex Kwan discusses how psychedelics like ketamine and psilocybin induce rapid neuroplastic changes in the brain, particularly in the prefrontal cortex, contrasting their effects with traditional antidepressants like SSRIs, and exploring their potential for treating depression and chronic pain through structural and functional brain alterations.

Key Takeaways:

• Ketamine & psilocybin rapidly increase dendritic spine density in the prefrontal cortex, enhancing neural connections within days, unlike SSRIs, which take weeks.
• These drugs show sustained neuroplastic changes in mice, lasting weeks to months after a single dose, suggesting long-term brain rewiring.
• Serotonin 2A receptor is critical for psilocybin’s neuroplastic effects, as precise genetic knockouts in adult mice eliminate spine growth.
• Unlike ketamine, psilocybin activates the insula, a brain region linked to chronic pain processing, hinting at new therapeutic potential.
• Both drugs induce similar gene expression patterns in areas like the prefrontal cortex and amygdala, but differ in specific regions like the insula.

Related episode:

• M&M #30: Psilocybin, Ketamine, Neuroplasticity & Imaging the Brain | Alex Kwan

*Not medical advice.

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Short Summary: The flaws of nutrition epidemiology with Dr. John Speakman

About the guest: John Speakman, PhD is a professor at the University of Aberdeen and runs a lab in Shenzhen, China, focusing on energy balance, obesity, and aging.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.

Episode Summary: Dr. John Speakman explores the pitfalls of nutrition epidemiology, a field that links diet to health outcomes like cancer and obesity but often produces contradictory results. They discuss flawed methods like 24-hour recalls and food frequency questionnaires, which rely on memory and are prone to bias, and introduce Speakman’s new tool using doubly labeled water to screen implausible dietary data. The conversation highlights systematic biases, such as under-reporting by heavier individuals, and emerging technologies like photo diaries and AI for better dietary tracking.

Key Takeaways:

• Nutrition epidemiology studies often contradict each other due to unreliable methods.
• Common techniques like 24-hour recalls & food frequency questionnaires suffer from memory issues, portion size issues, and systematic biases, often underestimating food intake.
• Heavier individuals (higher BMI) under-report food intake more, skewing associations between diet & obesity.
• Speakman’s tool, based on 6,500 doubly labeled water measurements, predicts energy expenditure to flag implausible dietary survey data.
• Emerging technologies, like smartphone photo diaries and AI food identification, promise more accurate dietary tracking than traditional surveys.
• Randomized controlled trials, not surveys, provide the most reliable dietary insights; single-day intake surveys linked to outcomes years later are dubious.
• Speakman advises ignoring most nutrition epidemiology headlines due to their inconsistency and lack of prognostic value for behavior change.

Related episode:

• M&M #132: Obesity Epidemic, Diet, Metabolism, Saturated Fat vs. PUFAs, Energy Expenditure,

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Short Summary: Cancer’s metabolic roots with Dr. Thomas Seyfried.

About the guest: Thomas Seyfried, PhD is a professor of biology at Boston College. He has researched cancer metabolism, epilepsy, and lipid biochemistry for over 40 years.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.

Episode Summary: Dr. Thomas Seyfried discusses the mitochondrial metabolic theory of cancer, challenging the dominant somatic mutation theory. He explores how cancer cells rely on fermentation due to defective oxidative phosphorylation, drawing on Otto Warburg’s work. Seyfried explains how ketogenic diets and nutritional ketosis can starve cancer cells by limiting glucose and glutamine, while sharing evidence from nuclear transfer experiments and clinical studies. The conversation also covers environmental factors driving cancer and the importance of metabolic flexibility for prevention.

Key Takeaways:

• Cancer is characterized by dysregulated cell growth, but Seyfried argues it stems from mitochondrial dysfunction, not just genetic mutations.
• Cancer cells ferment glucose & glutamine, unable to use fatty acids or ketones, making ketogenic diets a potential therapeutic tool.
• Nuclear transfer experiments show cancer traits reside in the cytoplasm, not the nucleus, challenging the somatic mutation theory.
• Environmental factors like processed foods, stress, and poor sleep disrupt mitochondrial function, increasing cancer risk.
• Seyfried’s glucose-ketone index helps monitor metabolic states to manage cancer & chronic diseases.
• Cancer rates are rising in younger people, possibly due to obesity, inflammation, and environmental toxins.
• Metabolic flexibility, cycling between ketosis and carb-based states, may mimic ancestral patterns and reduce chronic disease risk.

Related episode:

• M&M #215: Cancer Metabolism: Sugar, Fructose, Lipids & Fasting | Gary Patti

*Not medical advice.

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Short Summary: Heart health and the ketogenic diet, with expert insights from a cardiologist and researcher.

About the guest: Matthew Budoff, MD, is a preventive cardiologist and professor of medicine at UCLA School of Medicine.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Transcript and other information on Substack.

Episode Summary: Dr. Matthew Budoff discusses cholesterol, heart disease, and his study on the ketogenic diet’s impact on lean, metabolically healthy individuals with high LDL cholesterol. He explains LDL, HDL, and triglycerides, debunking myths about their direct link to heart disease, and emphasizes the importance of coronary calcium scans to assess plaque buildup. Budoff also covers statins, dietary cholesterol, and personalized heart health strategies.

Key Takeaways:

• LDL cholesterol is not a definitive predictor of heart disease; plaque buildup, assessed via coronary calcium scans, is a better indicator.
• Lean metabolically healthy people on a ketogenic diet may have high LDL without increased plaque progression after one year.
• Coronary calcium scans, costing ~$100, are recommended for men around age 40 and women around 45-50 to evaluate heart disease risk.
• Statins effectively lower LDL and can reverse soft plaque, but may be overprescribed for those without plaque buildup.
• Dietary cholesterol has minimal impact on blood cholesterol, as the liver produces ~85% of it.
• Ketogenic diet can aid weight loss & diabetes control but may cause high LDL in some lean individuals, known as lean mass hyper-responders.
• Plaque progression depends more on existing plaque than LDL levels in metabolically healthy ketogenic diet followers.
• Heart health varies widely due to genetics and other unknown factors, underscoring the need for personalized assessments.

Related episode:

• M&M #158: Ketosis & Ketogenic Diet: Brain & Mental Health, Metabolism, Diet & Exercise, Cancer, Diabetes | Dominic D'Agostino

*Not medical advice.

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Short Summary: The science of obesity and appetite regulation, blending genetics and neurobiology with practical insights

About the guest: Giles Yeo, PhD is a professor of molecular neuroendocrinology at the University of Cambridge. He leads a lab studying obesity and appetite regulation.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.

Episode Summary: Nick interviews Dr. Giles Yeo about the genetics and neurobiology of obesity, starting with the discovery of leptin in the obese mouse model, detailing its role in appetite regulation via the hypothalamus, and discussing GLP-1 drugs like Ozempic for weight loss. It delves into how genetic factors, like the leptin-melanocortin pathway, influence hunger, the heritability of body weight, and societal factors driving the obesity epidemic, emphasizing the interplay of biology and environment.

Key Takeaways:

• Leptin, discovered through the obese mouse, signals fat levels to the brain, but its absence causes severe obesity and infertility, as seen in rare human mutations.
• The hypothalamus, a key brain region, senses hormones like leptin and GLP-1, balancing hunger and satiety through POMC (anorexigenic) and AgRP (orexigenic) neurons.
• Body weight heritability is 40-70% at the population level, but this does not mean that 40-70% of someone’s body fat composition is due to genetic factors outside human control. Dr. Yeo unpacks how to think about it.
• GLP-1 drugs (e.g., Ozempic) mimic gut hormones to reduce appetite, offering some people 15-25% weight loss, but require long-term safety monitoring.
• According to Dr. Yeo, obesity reflects energy imbalance, but nutritional density matters more than calorie counting for health, and societal changes are needed to prevent it.

Related episode:

• M&M #132: Obesity Epidemic, Diet, Metabolism, Saturated Fat vs. PUFAs, Energy Expenditure, Weight Gain & Feeding Behavior | John Speakman

*Not medical advice.

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Short Summary: A mind-bending dive into evolutionary biology and health through a biophysicist’s lens, with Dr. Jack Kruse delivering provocative insights about biology, medicine, and health.

About the guest: Jack Kruse, MD, is a neurosurgeon known for integrating biophysics into medicine. He challenges conventional biochemistry with his “leptin prescription” and decentralized health approach.

Episode Summary: Dr. Jack Kruse joins host Nick Jikomes to explore the Great Oxygenation Event’s role in shaping life, linking it to modern health via biophysics over biochemistry. They discuss oxygen’s impact on metabolism, the significance of deuterium-depleted water, and sunlight’s influence on the leptin-melanocortin pathway. Kruse shares his dramatic weight loss journey using sunlight and cold therapy, critiques modern tech-driven obesity, and unveils a controversial history of SV40 in vaccines, tying it to cancer spikes.

Key Takeaways:

• The Great Oxygenation Event (2.1-2.4 billion years ago) drove life’s shift to oxygen-based metabolism, with cyanobacteria as key players.
• Kruse argues biophysics, not biochemistry, explains evolution, spotlighting light as life’s fundamental driver.
• Deuterium-depleted water is important for enabling our cells and mitochondria to use energy from the TCA cycle without “shocking” the body.
• Sunlight exposure boosts nitric oxide, reducing food needs via the leptin pathway, challenging diet norms.
• Kruse lost 133 pounds in 11 months using sunlight and cold therapy, inspiring his “leptin prescription.”
• He links obesity to indoor tech lifestyles, disrupting heme proteins and mitochondrial function.
• SV40, a virus in 1950s polio vaccines, may connect to cancer rises, a story Kruse says was buried by centralized science.

Related episode:

• M&M #196: Vaccine Contamination & Fiat Science | Kevin McKernan

*Not medical advice.

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Short Summary: A deep dive into the science of oxidative stress, antioxidants, aging, and neurodegenerative diseases like Alzheimer’s.

About the guest: Pamela Maher, PhD is a professor at the Salk Institute in San Diego, California, with a focus on neurodegenerative diseases, oxidative stress, and antioxidants.

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Episode Summary: Dr. Pamela Maher discusses her research on cell death mechanisms, including apoptosis and ferroptosis, and their roles in health and disease. They discuss how oxidative stress from reactive oxygen species can damage cells, the body’s antioxidant defenses like glutathione and studies on natural compounds—fisetin, curcumin, and cannabinol (CBN)—that may protect against brain cell loss. The conversation covers CBN’s mitochondrial benefits in aging mouse models and broader risk factors for dementia, like obesity and hearing loss, emphasizing early intervention.

Key Takeaways:

• Apoptosis is a controlled cell death process vital for development, while ferroptosis, linked to oxidative stress and iron, causes cells to burst and is tied to diseases like Alzheimer’s.
• Oxidative stress arises when reactive oxygen species overwhelm antioxidants, damaging DNA, proteins, and cell membranes, especially polyunsaturated fats.
• Glutathione, a key antioxidant, relies on cysteine and declines with age, but supplements like N-acetylcysteine might help, though tolerability varies.
• Cannabinol (CBN), a THC byproduct, protects mitochondria and improves memory in aging mice, hinting at therapeutic potential beyond cannabinoid receptors.
• Middle-age risk factors like visceral obesity, type 2 diabetes, and hearing loss significantly increase dementia risk, but hearing aids can reduce it.

Related episode:

• M&M #165: PUFAs in Brain Health & Disease, Dietary Fats, Brain Lipids, Nutrition | Richard Bazinet

*Not medical advice.

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Short Summary: A detailed examination of shamanism with anthropologist Manvir Singh, blending evolutionary theory and vivid storytelling.

About the guest: Manvir Singh, PhD is an anthropologist at the University of California, Davis. His new book, "Shamanism: The Timeless Religion," comes out on May 25, 2025.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.

Episode Summary: Dr. Manvir Singh discusses shamanism’s role as a universal human practice, exploring its roots in cultural evolution, cognitive tendencies, and persistence across history and modern society. They discuss how shamans use altered states to address uncertainty—like healing or divination—while examining shamanism’s interplay with centralized religion, its psychological benefits, and parallels in today’s world, from tech gurus to medical placebos.

Key Takeaways:

• Shamanism is a widespread cultural practice involving specialists who enter altered states to engage with unseen forces, often for healing or managing uncertainty.
• It’s not an archaic precursor to modern religion but a recurring expression of spiritual beliefs & practices, competing with other forms.
• Techniques vary widely—dance, music, psychedelics—but only about half of shamans historically used psychoactive substances.
• Modern parallels include tech CEOs and money managers who project exceptionalism to influence others, echoing shamanic charisma without trance.
• Open-label placebos (where patients know it’s fake) still work, suggesting rituals alone can trigger healing, much like shamanic practices.
• Singh sees shamanism as a cognitive technology, not inherently good or bad, shaping how we cope with chaos across cultures and time.

Related episode:

• M&M #86: Shamanism, Psychedelics, Social Behavior, Religion & Evolution of Human Culture | Michael Winkelman

*Not medical advice.

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Short Summary: How environmental chemical exposures affect neurodegenerative disease and health.

About the guest: Gary Miller, PhD is a Professor of Environmental Health Sciences at Columbia University. His research bridges pharmacology, toxicology, and neuroscience to explore neurodegeneration, particularly Parkinson’s and Alzheimer’s diseases.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.

Episode Summary: Dr. Gary Miller talks about neurodegenerative diseases like Parkinson’s and Alzheimer’s, exploring their age-driven nature, early detection challenges, and environmental risk factors such as pesticide exposure and head trauma. They discuss the emerging field of exposomics—studying lifetime chemical exposures—and its potential to uncover links between pollutants, diet, and disease, while highlighting protective factors like caffeine and nicotine, and the role of technology in advancing prevention and treatment.

Key Takeaways:

• Neurodegenerative diseases like Parkinson’s & Alzheimer’s worsen with age, but early intervention could slow progression & improve quality of life.
• Parkinson’s symptoms often appear after significant dopamine neuron loss, but subtle signs like handwriting changes or gait issues might be detectable earlier.
• Environmental factors, including pesticides & air pollution, increase neurodegeneration risk, while caffeine and nicotine surprisingly lower Parkinson’s incidence.
• The exposome—total lifetime exposure to chemicals—offers a new lens to study health, revealing how pollutants & diet interact with our biology.
• Ultra-processed foods & common chemicals like PFAS (in packaging) raise exposure levels, but simple steps like air filters or less processed diets can help reduce risks.

Related episode:

• M&M #145: Epigenetics, Hormones, Endocrine Disruptors, Microplastics, Xenoestrogens, Obesogens & Obesity, Inheritance of Acquired Characteristics | Bruce Blumberg

*Not medical advice.

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Short Summary: Do elephants and other animals have language-like abilities, such as the ability to use individual names to refer to themselves and others?

About the guest: Michael Pardo, PhD studies animal behavior at Cornell University, where he focused on animal communication and cognition. His work includes extensive field research with African elephants in Kenya.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.

Episode Summary: Michael Pardo, PhD talks about his research on animal communication, focusing on whether African savanna elephants use vocal "names" to address each other. They explore the broader context of vocal communication across species like dolphins, parrots, and marmosets, discussing how these systems compare to human language and what they reveal about its evolution. Dr. Pardo shares details of his fieldwork in Kenya, elephant social structures, and their behaviors like mourning the dead, while also touching on the challenges and joys of studying animals in their natural habitats.

Key Takeaways:

• Elephants may use unique vocal rumbles to address specific individuals.
• Dolphins use signature whistles as "calling cards," sometimes imitating others’ whistles to get their attention, hinting at a form of naming.
• Elephant society features female-led family groups and dispersing males.
• Elephants show intriguing behaviors like visiting carcasses and covering them with dirt, suggesting an awareness of death uncommon in most animals.
• Human language evolution may have evolved gradually from simpler communication systems, as seen in various species, rather than emerging suddenly.
• Studying less charismatic animals like chickens could uncover surprisingly complex communication, broadening our understanding of cognition in nature.

Related episode:

• M&M #20: Language, Symbolic Cognition, Evolution, Origins of the Human Mind | Terrence Deacon

*Not medical advice.

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Short Summary: The science of cancer and immunity with Dr. Roychoudhuri, blending cutting-edge research with everyday implications like aspirin’s role in fighting tumor metastasis.

About the guest: Rahul Roychoudhuri, PhD is a Professor of Cancer Immunology at the University of Cambridge. His research bridges basic science and clinical applications, focusing on immune responses to cancer development and spread.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.

Episode Summary: The immune system’s role in detecting and fighting cancer, particularly how cancer cells evade immunity through selection pressures and microenvironment manipulation. They explore cancer initiation via mutations and inflammation, metastasis mechanics, and a surprising link between low-dose aspirin and reduced cancer spread, spotlighting new research on T cells and thromboxane. The discussion ties in dietary fats, aspirin’s anti-inflammatory and anti-clotting effects, and the potential for new therapies to prevent metastasis.

Key Takeaways:

• The immune system constantly surveils and eliminates early cancer cells, but surviving cancers evolve to dodge detection.
• Inflammation can both spark cancer growth and be exploited by tumors to suppress helpful immune responses.
• Cancer metastasis, responsible for ~90% of cancer deaths, involves cells breaking off, traveling, and adapting to new sites.
• New research shows aspirin may curb metastasis by lowering thromboxane, a lipid-derived blood clotting factor.
• Human data hints aspirin reduces metastasis risk in cancers like breast and colorectal, but trials are ongoing.
• Daily low-dose aspirin (75-100 mg) is used for heart health, yet its cancer benefits need more study. 600 mg per day has been observed to reduce metastasis rates in colon cancer patients, but chronic use of that dose carries some risk (ulcers, bleeding).

*Not medical advice.

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Short Summary: How dietary fructose affects the growth rate of cancer.

About the guest: Gary Patti, PhD is a professor at Washington University in St. Louis, holding appointments in chemistry, medicine, and genetics

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.

Episode Summary: Nick Jikomes talks to Dr. Patti, exploring how cancer cells metabolize sugars like glucose and fructose, focusing on a recent study showing fructose indirectly boosts tumor growth in mice via liver-produced lipids called LPCs. The discussion covers cancer biology basics, Warburg effect, tumor microenvironments, and systemic metabolic impacts of cancer, while also touching on dietary implications, fasting, and the complexities of nutrient use in cancer progression.

Key Takeaways:

• Cancer cells often rely heavily on glucose, excreting it as lactate even when oxygen is available (Warburg effect), but take up more than their mitochondria can handle.
• In a study, high fructose diets accelerated tumor growth in mice by 4x, not because cancer cells use fructose directly, but because the liver converts it to LPCs, which tumors use to build membranes.
• Tumors are not just cancer cells; they recruit healthy cells in their microenvironment, and their metabolic effects ripple across the entire body, altering distant tissues.
• Excessive fructose consumption may worsen tumor growth, but cutting it poses little risk and could benefit cancer patients, pending human studies.
• Fasting may reduce cancer initiation risk in animals, but its effect on existing tumors is less clear and could worsen wasting (cachexia) in late stages.
• The body tightly regulates blood glucose via the liver, so simply cutting dietary glucose won’t starve tumors, highlighting cancer’s metabolic adaptability.

Related episode:

• M&M #200: Dietary Fats & Seed Oils in Inflammation, Colon Cancer

*Not medical advice.

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Short Summary: How diet shapes the gut microbiome and impacts health, with microbiologist Dr. Peter Turnbaugh breaking down the complex science.

About the guest: Peter Turnbaugh, PhD is a professor of microbiology and immunology at the University of California, San Francisco, where he leads a lab studying the gut microbiome’s role in nutrition and drug response.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.

Episode Summary: Nick talks to Peter Turnbaugh discuss the pitfalls of oversimplified diet labels in research, Turnbaugh’s studies comparing plant-based and animal-based diets in humans, and how these shifts rapidly alter gut microbes and short-chain fatty acid profiles.

Key Takeaways:

• The term “high-fat diet” in research is often misleading, as it can include high carbs and vary widely, complicating study comparisons.
• In a 2014 study, switching humans to a plant-based (high-fiber) or animal-based (ketogenic, no-fiber) diet changed their gut microbiome within one day, showing its remarkable adaptability.
• Ketogenic diets reduce Bifidobacterium in the gut, which may lower inflammation-linked immune cells (Th17), potentially aiding conditions like multiple sclerosis.
• Short-chain fatty acids (e.g., butyrate) don’t just come from fiber; they persist even on zero-fiber ketogenic diets, hinting at alternative microbial pathways.
• Gut microbes can activate or deactivate drugs, like antibiotics or digoxin, suggesting microbiomes may explain why drugs work differently across individuals.
• Ketone bodies like BHB alone can mimic some ketogenic diet effects on the microbiome and immunity, simplifying research and hinting at therapeutic potential.

Related episode:

• M&M #203: Metagenomics, Microbiome Transmission, Gut Microbiome in Health & Disease | Nicola Segata

*Not medical advice.

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Short Summary: The science of diabetes with Dr. Scott Soleimanpour, blending personal insights and cutting-edge research that gets into mitochondrial biology and more.

About the guest: Scott Soleimanpour, MD, is a physician-scientist at the University of Michigan, where he runs a lab studying pancreatic beta cell biology and mitochondrial quality control in diabetes.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.

Episode Summary: Nick Jikomes interviews Dr. Scott Soleimanpour about the biology of diabetes, exploring the pancreas’s dual role in digestion and blood sugar regulation via beta cells, which produce insulin. They discuss type 1 diabetes as an autoimmune condition with rising incidence and complex beta cell issues, and type 2 as a progressive disease tied to beta cell failure, not just obesity. The conversation covers mitochondrial function in beta cells, lifestyle factors like diet, and the limits of current treatments, offering practical advice for prevention and management.

Key Takeaways:

• The pancreas has two parts: the exocrine (98%) makes digestive enzymes, while the endocrine (1-2%) regulates blood sugar with hormones like insulin from beta cells.
• Type 1 diabetes involves autoimmunity and intrinsic beta cell defects, with rates increasing due to environmental factors, not just genetics.
• Type 2 diabetes hinges on beta cell dysfunction, not obesity alone—only 1 in 5 overweight people develop it, showing other factors matter.
• Beta cells are energy-intensive and long-lived, relying on mitochondria; stress from overwork (e.g., excess insulin demand) can lead to failure.
• Current diabetes drugs don’t rejuvenate beta cells; only TZDs (rarely used) preserve function, highlighting a gap in treatment.

Related episode:

• M&M #140: Obesogens, Oxidative Stress, Dietary Sugars & Fats, Statins, Diabetes & the True Causes of Metabolic Dysfunction & Chronic Disease | Robert Lustig

*Not medical advice.

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Short Summary: A rare, insider’s look at the messy realities of scientific research with Stanford’s Dr. John Ioannidis. The good, the bad, and the ugly about how scientific research actually works.

About the guest: John Ioannidis, MD, PhD is a professor at Stanford University in medicine, epidemiology, population health, and biomedical data science, with an MD from the University of Athens and a PhD from Harvard in biostatistics. He directs the Meta-Research Innovation Center at Stanford (METRICS), focusing on improving research methods and practices. Renowned for his paper “Why Most Published Research Findings Are False,” he’s among the most cited scientists globally, tackling biases and reproducibility in science.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.

Key Takeaways:

• Science’s “replication crisis” isn’t new—it’s baked into how tough and bias-prone research is, hitting all fields, not just “soft” ones like psychology.
• Ioannidis’s famous claim, “most published findings are false,” holds up: stats show many “significant” results are flukes due to weak studies or bias.
• Peer review’s a mixed bag—only a third of papers improve, and unpaid, tired reviewers miss a lot, letting shaky stuff slip through.
• Publishing’s a $30 billion game with 50,000+ journals; big players like Elsevier rake in huge profits from subscriptions and fees, often over $10,000 per paper.
• Researchers game the system—think fake co-authorships or citation cartels—boosting metrics like the H-index, which tracks papers with matching citation counts.
• Ioannidis’s early COVID-19 fatality rate (0.2-0.3%) was spot-on but sparked a firestorm as politics warped science into “clan warfare.”
• NIH funding’s clogged by red tape and favors older researchers, starving young innovators and risky ideas that could shake things up.
• He’s building tools like a public database of scientist stats (4 million downloads!) to spotlight gaming and push for transparent, fair research.

*Not medical advice.

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Short Summary: Personalized health monitoring with Professor Michael Snyder, blending cutting-edge science with practical tips and actionable insights.

About the guest: Michael Snyder, PhD is a Professor of Genetics at Stanford University School of Medicine. He directs the Center for Genomics and Personalized Medicine, which focuses on big data and health innovation. Snyder holds a PhD from Caltech and completed postdoctoral work at Stanford. His career has spanned yeast genomics to human health profiling. Currently, he leads research on advanced molecular and wearable technologies while spinning off companies like Q Bio to translate findings into real-world health solutions.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.

Episode Summary: Nick talks to Dr. Michael Snyder about transforming medicine through personalized health monitoring, leveraging tools like wearables, continuous glucose monitors, and deep molecular profiling. They explore how diet, microbiome, and genetics shape metabolic health, delving into Snyder’s research on diabetes subtypes, short-chain fatty acids, and aging patterns. The conversation also covers practical technologies available today, like smartwatches and home blood tests, and their potential to catch diseases early and extend healthy lifespans.

Key Takeaways:

• Medicine is shifting from sick care to proactive health care using comprehensive data from wearables and molecular profiling.
• Diabetes has many subtypes, not just type 1 or 2, and treatments like drugs or diet should match an individual’s specific profile.
• Dietary fiber boosts gut health by producing short-chain fatty acids, which influence gene expression and may reduce leaky gut risks.
• Aging isn’t linear—big changes spike in the 40s and 60s, varying by person (e.g., heart, kidneys, metabolism), offering chances to adjust lifestyles early.
• Wearables like fitness watches can detect illnesses (e.g., COVID, Lyme) days before symptoms by tracking heart rate shifts.
• Continuous glucose monitors reveal surprising food responses, guiding personalized diets.

*Not medical advice

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Short Summary: Insider’s look at the COVID-19 pandemic response from a seasoned epidemiologist, unraveling myths and lessons with straightforward science.

About the guest: Martin Kulldorff, PhD is an epidemiologist and biostatistician with decades of experience in infectious disease monitoring and vaccine safety. He was formerly a professor at Harvard Medical School.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack. Partial versions are available elsewhere. Full transcript and other information on Substack.

Episode Summary: Dr. Martin Kulldorff discusses the COVID pandemic response, reflecting on the controversial Great Barrington Declaration, which opposed lockdowns in favor of protecting the vulnerable. They explore the virus’s fatality rates, asymptomatic spread, and vaccine efficacy, contrasting textbook epidemiology with real-world decisions. He critiques institutional failures, like the CDC’s misleading claims. He shares optimism for future pandemics with better leadership and public awareness.

Key Takeaways:

• Lockdowns ignored basic public health principles, causing collateral damage like missed cancer screenings, while Sweden’s focused protection approach led to lower excess mortality.
• Early data showed COVID’s risk was 1000x higher for older people, yet lockdowns didn’t prioritize them, unlike textbook strategies.
• Asymptomatic spread made containment impossible, unlike Ebola, where isolation works due to clear symptoms.
• Natural immunity was downplayed despite 2500 years of evidence, leading to wasted vaccines on those already immune.
• CDC falsely claimed vaccines stopped transmission, eroding trust when people got sick anyway, fueling vaccine skepticism.
• mRNA vaccine boosters lack proper trials, and their long-term effects need rigorous study, not assumptions.
• Kulldorff’s new Journal of the Academy of Public Health pushes open peer review to rebuild trust in science.

Related episode:

• M&M #100: Infectious Disease, Epidemiology, Pandemics, Health Policy, COVID, Politicization of Science | Jay Bhattacharya

*Not medical advice.

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Short Summary: Thyroid biology, offering insights into its role in metabolism, development, and longevity, making it a fascinating listen for those interested in how our bodies manage energy and health across the lifespan.

Guest: Diana van Heemst, PhD is a biologist at Leiden University Medical Center, specializing in gerontology and geriatrics. Her research focuses on the neuroendocrine biology of aging and longevity in humans, particularly involving thyroid functions.

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Full Summary: Dr. Diana van Heemst explores the thyroid's critical role in metabolism, growth, development, and transitions across life stages. It discusses the thyroid's evolutionary history, its location in the neck, and how it functions through hormone secretion, specifically T3 and T4. The conversation covers the importance of nutrients like iodine and selenium, the impact of thyroid hormone on various bodily functions, and the implications for health conditions like hypothyroidism and hyperthyroidism. It also touches on how thyroid activity might relate to longevity.

Key Takeaways:

• Thyroid Hormones: T3 and T4 are crucial, with T3 being the active form that regulates metabolism, heart rate, and cognitive functions.
• Iodine and Selenium: Essential for thyroid hormone synthesis; iodine is unique to thyroid hormones, while selenium is vital for the enzymes that regulate hormone availability.
• Hypothyroidism vs. Hyperthyroidism: Hypothyroidism is more common, especially in older age due to autoimmune issues, leading to symptoms like fatigue and cold sensitivity. Hyperthyroidism can result from iodine excess or autoimmune conditions like Graves' disease.
• Developmental Role: Thyroid hormones are vital for major developmental transitions, from birth to puberty, impacting brain development and metabolic adaptation.

*Not medical advice.

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Short Summary: The complexities of neurodegenerative disease, particularly Alzheimer's, environmental influences like glyphosate, and the crucial role of nutrients like choline, with actionable insights into brain health management.

About the guest: Dr.Ramon Valazquez is an Assistant Professor at Arizona State University, leading a research lab at the Neurodegenerative Disease Research Center. His work focuses on environmental factors related to Alzheimer's and other dementias, alongside developing therapeutic strategies.

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Episode Summary: Dr. Ramon Velazquez explores neurodegenerative disease, with a deep dive into Alzheimer's, its pathophysiology including amyloid beta plaques and tau pathology. It examines the controversy around these proteins' roles in disease progression, the influence of environmental toxins like glyphosate on brain health, and the preventive potential of nutritional interventions, particularly choline.

Key Takeaways:

• Neurodegenerative Disease Basics: Alzheimer's disease involves both amyloid beta plaques and tau tangles, with tau pathology more closely linked to clinical symptoms.
• Environmental Impact: Glyphosate, a common herbicide, can cross into the brain, potentially exacerbating neurodegenerative pathways through inflammation.
• Choline: Essential for brain function and fat metabolism, it’s often deficient in diets, particularly plant-based ones. Adequate intake might prevent or mitigate cognitive decline and related diseases.
• Preventive Measures: Early nutritional intervention, like maintaining choline levels, could be vital for preventing neurodegenerative diseases. However, once symptoms are present, such interventions might not reverse existing pathology.

Related episode:

• M&M #145: Epigenetics, Hormones

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Short Summary: The science of glycosylation, its impact on health, and potential treatments for congenital disorders of glycosylation (CDGs).

About the guest: Dr. Eva Morava is a pediatric geneticist originally from Hungary, who has specialized in inborn errors of metabolism, particularly CDGs. She has a background in pediatrics and genetics from training in Hungary and the U.S. and is director of the Inherited Metabolic Disorders Section at GGS.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and to everyone on YouTube. Partial versions are available elsewhere.

Episode Summary: Dr. Eva Morava discusses the critical role of glycosylation in biology, where sugars are not just used for energy but in modifying proteins to perform their functions. She explains how defects in this process lead to CDGs, a group of rare genetic disorders. The conversation covers the mechanics of glycosylation, clinical presentations of CDGs, current research on treatments including dietary interventions and gene therapy, and the broader implications of glycosylation in health, such as in liver disease and cancer.

Key Takeaways:

• Glycosylation Basics: Sugars are attached to proteins (glycosylation) to modify their structure and function, influencing everything from clotting to immune response.
• CDGs: These disorders are caused by genetic defects in the glycosylation process, leading to a wide array of symptoms because many proteins require glycosylation to function correctly.
• Clinical Variability: CDGs can range from severe, multi-systemic presentations to relatively mild cases, affecting life expectancy and quality of life variably.
• Therapeutic Approaches: Current research includes drug repurposing for enzyme activity enhancement, dietary interventions with special sugars like mannose, and gene therapy, with some trials underway.
• Liver Connection: A significant portion of glycosylation occurs in the liver; thus, liver diseases like non-alcoholic fatty liver disease can impact glycosylation.

*Not medical advice.

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Short Summary: How human culture and psychology have evolved, particularly exploring the unique psychological traits of "WEIRD" (Western, Educated, Industrialized, Rich, Democratic) societies, providing insights into why our minds and societies are the way they are today.

About the Guest: Joe Henrich, PhD is a professor of human evolutionary biology at Harvard University. His research focuses on applying evolutionary theory to understand the human mind and culture, particularly how cultural evolution has led to the emergence of WEIRD psychology.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and to everyone on YouTube. Partial versions are available elsewhere.

Key Takeaways:

• WEIRD Psychology: WEIRD stands for Western, Educated, Industrialized, Rich, and Democratic, highlighting unique psychological traits like individualism and analytic thinking which are not universal but specific to Western societies.
• Marriage & Kinship: The Western Church's marriage policies, promoting monogamy and the nuclear family, contributed to the dissolution of extended kinship networks, fostering individualism in Western societies.
• Institutional Influence: Institutions in WEIRD societies, like universities and legal systems, focus on individual rights and mental states, contrasting with other cultures emphasizing group or kin loyalty.
• Modern Challenges: Henrich touches on current issues like the impact of dating apps on mating markets, potentially leading to social instability due to increased male-female inequality in mating success.
• Future of Religion and Culture: The conversation speculates on the future evolution of religion and cultural practices, suggesting that religions fostering high fertility and communal support might gain prominence.

Related episode:

• M&M #129: Biological Sex, Sexual Selection, Sex Behavior, Mating Strategies, Sexual Orientation, Monogamy & Polygyny | David Puts

*Not medical advice.

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Short Summary: Deep dive into systems biology and personalized medicine, exploring how technology and data can revolutionize health care, artificial intelligence, biotechnology, and the future of medicine.

About the Guest: Dr. Lee Hood is a pioneering scientist with a 60-year career in biology, notably at Caltech and the University of Washington. He co-founded the Institute for Systems Biology and has significantly contributed to molecular immunology and the Human Genome Project, holding a PhD in biology.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and to everyone on YouTube. Partial versions are available elsewhere.

Key Takeaways:

• Systems Biology: Understanding complex biological systems by analyzing how individual components interact.
• Data-Driven Health: Use of genomic and phenomic data can lead to personalized health strategies, enhancing wellness and preventing chronic diseases before they manifest.
• AI in Medicine: AI can augment human capabilities in medicine, acting as a vast knowledge base to assist physicians in diagnosis and treatment, potentially leading to a partnership model between AI and human doctors.
• Chronic Disease: Much of the chronic disease burden could potentially be mitigated through lifestyle changes rather than solely through pharmaceutical interventions.
• Future Drug Development: The traditional focus on single-target drugs might shift towards multi-modal strategies, recognizing diseases like Alzheimer's might be a metabolic disorder.
• Peptides and New Therapies: Small peptide drugs are emerging as potential new treatments due to their ability to interact with a range of biological molecules, offering new possibilities beyond traditional small molecule drugs.
• Environmental Impact on Health: While personal behavior significantly influences health outcomes, environmental factors like exposure to toxins can also play critical roles in disease development.

Related episodes:

• M&M #204

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Short Summary: Deep dive into preventive medicine, personalized nutrition, and systems biology, providing listeners with actionable insights on optimizing health through diet & microbiome management.

About the guest: Momo Vuyisich is a biologist with a background in government science, focusing on drug development before shifting to preventive medicine. He holds a PhD in biochemistry and is currently Chief Science Officer of Viome, a startup company dedicated to personalized health through microbiome analysis.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and for free on YouTube. Partial versions are available elsewhere.

Episode Summary: Dr. Vuyisich discusses the transformative potential of preventive medicine by drawing parallels between human health and systems biology, particularly through the lens of the gut microbiome. He explains how Viome uses comprehensive testing (stool, blood, saliva), providing personalized dietary and supplement recommendations based on individual physiological data. Covers the complexity of diseases like IBD, the impact of modern lifestyle on our microbiome, and more.

Key Takeaways:

• Disconnection from Nature: Modern lifestyles have disrupted our symbiotic relationship with nature, leading to microbiome degradation through factors like antibiotics, preservatives, and hygiene practices.
• Personalized Nutrition: Viome's approach involves tailoring food recommendations & supplements to an individual's unique microbiome and physiological needs, highlighting that food impacts can vary greatly between individuals.
• Testing for Prevention: Regular testing with tools like Viome's full body intelligence test can help in making informed dietary changes to prevent diseases before they manifest.
• Lifestyle Over Medication: Many chronic conditions can potentially be managed or prevented through lifestyle adjustments rather than lifelong medication, emphasizing the need for a preventive rather than reactive strategy.

Related episodes:

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Short Summary: A deep dive into the enigmatic world of sleep, exploring its biological functions, evolutionary origins, and diverse manifestations across different species.

About the Guest: Nicola Segata, PhD is a professor at the University of Trento in Italy.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and on YouTube. Partial versions are available elsewhere.

Episode Summary: Dr. Segata explains metagenomics, the study of genetic material from multiple species, and how it has revolutionized microbiome research; microbiome transmission from mother to child; stability and plasticity of the microbiome throughout life stages; obesity and cancer; influence of diet, lifestyle, and medications like antibiotics on microbiome composition.

Key Takeaways:

• Microbiome Variability: The human microbiome varies significantly between individuals and is influenced by genetics, environment, diet, and lifestyle. Thus, personalized approaches to microbiome health may be necessary.
• Transmission and Acquisition: Microbes are transmitted vertically from mother to child at birth and horizontally through personal interactions. This transmission can influence health outcomes over one's lifetime.
• Impact of Diet and Drugs: Diet, particularly coffee consumption, can significantly shape the microbiome, with some bacteria growing in response to specific dietary components. Medications like antibiotics and proton pump inhibitors can also markedly alter microbial communities.
• Health Implications: The microbiome is linked to various health conditions, from metabolic diseases to cancer, with some treatments like fecal microbiota transplantation showing promise in altering microbiome composition for health benefits.
• Ancient vs. Modern Microbiomes: Studies on ancient microbiomes, like the Iceman's, suggest that modern urban microbiomes differ from those of our ancestors, potentially impacting modern health issues.

Related episodes:

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Short Summary: A deep dive into the enigmatic world of sleep, exploring its biological functions, evolutionary origins, and the diverse manifestations across different species.

Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and on YouTube. Partial versions are available elsewhere.

About the Guest: Vlad Vyazovskiy, PhD is a Professor of Sleep Physiology at the Department of Physiology, Anatomy, and Genetics at Oxford University.

Key Takeaways:

• Sleep as a Mystery: Despite extensive research, the fundamental reason why animals sleep remains elusive, with no comprehensive theory yet agreed upon.
• Local Sleep Phenomenon: Sleep might not be a whole-brain event; even within a sleeping brain, different areas can be in different states of activity or rest.
• Sleep in Animals: Sleep varies widely among species, from micro-sleeps in penguins to unihemispheric sleep in dolphins, suggesting sleep could serve multiple, context-dependent functions.
• Synaptic Homeostasis: The hypothesis suggests that sleep could be crucial for renormalizing synaptic connections formed during wakefulness, although this idea is still under scrutiny.
• Hibernation & Torpor: These states relate to sleep but involve significant metabolic changes, possibly acting as survival mechanisms by conserving energy and reducing detectability by predators.
• Psychedelics & Sleep: Research shows psychedelics like 5-MeO-DMT can induce states where animals show signs of sleep in their brain activity while physically active, hinting at complex interactions between brain states and consciousness.

Related episodes:

• M&M #43: Sleep, Dreaming, Deep Neural Networks, Machine Learning & Artificial Intelligence, Overfitted Brain Hypothesis, Evolution of Fiction & Art | Erik Hoel
• M&M #16: Sleep, Dreams, Memory & the Brain | Bob Stickgold

*Not medica

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About the Guest: Alex Wiltschko holds a PhD in neuroscience from Harvard, focusing on olfaction. He transitioned from academic research to AI at Google before founding Osmo, where he applies his expertise in digitizing scents. He aims to innovate in areas like fragrance design and health applications.

Episode Summary: Dr. Wiltschko explores the science of smell, discussing the divide between aroma and olfaction studies and how biological metabolism influences scent. He explains how only a tiny fraction of molecules emitted by strawberries are responsible for their smell, illustrating the precision of olfactory perception. The conversation also covers how Osmo is working to digitize scent, creating technology for safer, custom fragrances and potential future applications like non-invasive disease detection through scent.

Key Takeaways:

• Aroma vs. Olfaction: There's a significant distinction in how the chemistry of scent creation (aroma) and brain processing of scents (olfaction) are studied, with little crossover between these fields.
• Biological Metabolism and Scent: Scent molecules are often byproducts of biological processes, with a complex relationship to nutrition and survival cues.
• Digitizing Scent: Osmo is pioneering the use of AI to digitize and manipulate scents, potentially revolutionizing fragrance design and detection technologies.
• Fragrance Innovation: The company focuses on creating unique, safe, and affordable fragrances for smaller brands, leveraging AI for quick design and production.
• Health Applications: There's potential for scent technology in health, like detecting diseases early through the volatile chemicals humans emit.

Related episodes:

• M&M #114: Marijuana, Plant Chemistry, Terpenes, Volatile Sulfur Compounds, Cannabis Industry, What Pungent Weed Smells Like & Why | Iain Oswald
• M&M #22: Machine Learning, Art

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Podcast episodes are fully available to paid subscribers on the M&M Substack and on YouTube. Partial versions are available elsewhere.

About the Guest: Alex Wiltschko holds a PhD in neuroscience from Harvard, focusing on olfaction. He transitioned from academic research to AI at Google before founding Osmo, where he applies his expertise in digitizing scents. He aims to innovate in areas like fragrance design and health applications.

Episode Summary: Dr. Wiltschko explores the science of smell, discussing the divide between aroma and olfaction studies and how biological metabolism influences scent. He explains how only a tiny fraction of molecules emitted by strawberries are responsible for their smell, illustrating the precision of olfactory perception. The conversation also covers how Osmo is working to digitize scent, creating technology for safer, custom fragrances and potential future applications like non-invasive disease detection through scent.

Key Takeaways:

• Aroma vs. Olfaction: There's a significant distinction in how the chemistry of scent creation (aroma) and brain processing of scents (olfaction) are studied, with little crossover between these fields.
• Biological Metabolism and Scent: Scent molecules are often byproducts of biological processes, with a complex relationship to nutrition and survival cues.
• Digitizing Scent: Osmo is pioneering the use of AI to digitize and manipulate scents, potentially revolutionizing fragrance design and detection technologies.
• Fragrance Innovation: The company focuses on creating unique, safe, and affordable fragrances for smaller brands, leveraging AI for quick design and production.

Related episodes:

• M&M #114: Marijuana, Plant Chemistry, Terpenes, Volatile Sulfur Compounds, Cannabis Industry, What Pungent Weed Smells Like & Why | Iain Oswald
• M&M #22: Machine Learning, Artificial Intelligence, Animal Behavior & Giving Computers a Sense of Smell | Alex Wiltschko

*Not medical advice.

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This episode educates on the complex science of dietary lipids (fats) and inflammation and provides actionable advice for managing your health through dietary choices.

Note: Full episodes are available to paid subscribers on the M&M Substack and are free on YouTube. Partial versions are available elsewhere.

About the guest: Tim Yeatman, MD is a surgical oncologist and professor of surgery at the University of South Florida, also serving as an Associate Center Director for Translational Research and Clinical Innovation at the Tampa General Cancer Institute. Ganesh Halade, PhD is an Associate Professor in the Department of Internal Medicine, focusing on cardiovascular diseases with research centered on inflammation and resolution signaling.

Episode summary: Explores the link between dietary lipids, particularly omega-6 fatty acids from seed oils, chronic inflammation, and cancer. It starts with a historical perspective on cancer as an inflammatory disease, referencing the work of Rudolf Virchow, and delves into how modern diets have shifted to include an imbalance of omega-6 to omega-3 fatty acids, leading to chronic inflammation. Includes insights from a recent study by Yeatman and Halade on lipid dysregulation in colon cancer, explaining how this imbalance can contribute to the development of cancer and other diseases. The conversation also touches on lifestyle factors like diet, exercise, and sleep, and how they interact with lipid metabolism to affect health outcomes.

Related episodes:

• M&M #134: Omega-6-9 Fats, Vegetable & Seed Oils, Sugar, Processed Food, Metabolic Health & Dietary Origins of Chronic Inflammatory Disease | Artemis Simopoulos
• M&M #136: Seed Oils, Omega-6 PUFAs, Inflammation, Obesity, Diabetes, Chronic Disease & Metabolic Dysfunction | Chris Knobbe

*This content is never meant to serve as medical advice

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About the guest: Ben Potter, PhD is an archaeologist & Professor of Anthropology at the University of Alaska-Fairbanks. James Chatter, PhD is a retired archaeologist and paleontologist. They recently published a paper on the diet of the Clovis people of North America at the end of the last Ice Age.

Episode summary: Nick talks to Dr. Potter & Dr. Chatters about: the Clovis culture and initial human colonization of the Americas; human diet since the last Ice Age; ancient human diets; hunting of Mammoths and other large herbivores; Clovis technology & culture, including projectile weapons; and more.

Related episodes:

• M&M #160: Diet, Hunting, Culture and Evolution of Paleolithic Humans & Hunter Gatherers | Eugene Morin
• M&M #154: Evolution & Genetics of Human Diet, Metabolism, Disease Risk, Skin Color and Origins of Modern Europeans | Eske Willerslev

*This content is never meant to serve as medical advice

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Podcast episodes are fully available to paid subscribers on the M&M Substack and full video versions are free on YouTube. This episode will not be posted on YouTube due to the controversial nature of the content.

About the guest: Jessica Rose, PhD is a computational biologist who has been studying and analyzing data from the Vaccine Adverse Event Responding System (VAERS) related to COVID.

Episode summary: Nick and Dr. Rose discuss: Vaccine Adverse Event Responding System (VAERS); analysis of VAERS data for COVID; mRNA technology; spike protein persistence & lipid nanoparticles; common adverse events reported for the Pfizer & Moderna shots; myocarditis & menstrual irregularities; IgG4 antibodies, molecular mimicry & autoimmunity; and more.

Related episodes:

• M&M #196: Vaccine Contamination & Fiat Science | Kevin McKernan
• M&M #100: Infectious Disease, Epidemiology, Pandemics, Health Policy, COVID, Politicization of Science | Jay Bhattacharya

*This content is never meant to serve as medical advice

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Full episodes are available to paid subscribers on the M&M Substack and free on YouTube. This is a free, partial version.

About the guest: Andrew Cutler, PhD is a machine learning engineer who has studied natural language processing, psychometrics & personality using quantitative methods. He writes about the origins of consciousness on his Substack, "Vectors of Mind"

Episode summary: Nick and Dr. Cutler discuss: language & recursion; human evolution & the origins of "higher" consciousness; symbolic cognition, social intelligence & metacognition; creation myths & ritual cults throughout history; snake cults in human history; the intentional ingestion of snake venom in the present-day; the "Stone Ape Theory" of consciousness; the origins of civilization; and more.

Related episodes:

• M&M #141: Evolution, Language, Domestication, Symbolic Cognition, AI & Large Language Models | Terrence Deacon
• M&M #1: Psychedelics, Civilization, Religion, Death & Plant Medicine | Brian Muraresku

*This content is never meant to serve as medical advice

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About the guest: Rosemary Bagot, PhD is an Associate Professor in the Department of Psychology at McGill University and the Canada Research Chair in Behavioural Neurogenomics. Her lab studies the neurobiology of stress at the molecular, circuit, and behavioral levels.

Episode summary: Nick and Dr. Bagot discuss the hypothalamic-pituitary-adrenal (HPA) Axis, cortisol and hormonal responses to stress; neural circuits related to the perception of threats & stressors; resilience & early life stress; sex differences & individual variability in stress response; epigenetics & transgenerational effects of stress; and more.

Related episodes:

• M&M #183: Calorie Restriction & Fasting: Aging, Immunity, Health Biomarkers, Stress, Genetics | Gary Churchill
• M&M #156: Psychology of Stress, Resilience, Emotion & Child Development | Stephen Sideroff

*This content is never meant to serve as medical advice

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About the guest: Jibran Khokhar, PhD is Associate Professor of Anatomy & Cell Biology at Western University in Ontario. His lab studies the neurobiology of the co-occurrence of psychiatric illnesses like schizophrenia with substance use disorders.

Episode summary: Nick and Kevin discuss high comorbidity among mental illness, the dopamine reward system, antipsychotics & other psychiatric drugs; the relationship between THC (marijuana) and psychosis; sex differences in the brain; nicotine e-cigarettes (vaping) compared to smoking; and more.

Related episodes:

• M&M #113: Alcohol Toxicity, Vaping vs. Smoking, Tobacco, Nicotine, Marijuana, Cannabis Terpenes, THC, Toxicology, Health Effects of Vaping | Echo Rufer
• M&M #93: Marijuana, Cognition, Psychosis, Addiction, Cannabinoids, THC, CBD, THCV | Amir Englund

Special offer: Use MINDMATTERSPECIAL2 to get a free 1-year premium subscription to Consensus, a new AI-powered research tool to help you find the best science, faster ($150 value, limited time offer).

*This content is never meant to serve as medical advice.

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About the guest: Kevin McKernan is the founder and Chief Science Officer of Medicinal Genomics. He has worked in biotechnology since the early 1990s, when he was involved in the Human Genome Project.

Episode summary: Nick and Kevin discuss: components of the COVID vaccines, including modified mRNA & lipid nanoparticles; DNA contamination in COVID vaccines; vaccine adverse events & IgG4 immune modulation; concerns with COVID PCR testing; origins of the SARS-CoV-2 virus; Fiat Science from the AIDS epidemic to today; how Big Pharma works with government regulators; decentralized medicine; and more.

Related episodes:

• M&M #149: DNA & RNA Biology, mRNA Vaccines, Vax Contamination & Side Effects, Spike Protein, Ivermectin, Hop Latent Viroid | Kevin McKernan
• M&M #97: How Did the SARS-CoV-2 Virus Originate? | Alex Washburne

Special offer: Use code MINDMATTERSPECIAL for a limited time to get a free 1-year premium subscription to Consensus, a new AI-powered research tool to help you find the best science, faster.

*This content is never meant to serve as medical advice

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About the guest: Andrzej Slominski, MD, PhD is a dermapathologist and skin biologist who has spent decades studying skin biology, especially regarding endocrinology (hormones), stress response, photobiology, and more.

Episode summary: Nick and Dr. Slominski discuss: hormone production in the skin; vitamin D photobiology; risks and benefits of UVB light; skin cancer & sunscreen; protective effects of melatonin production in the skin; and more.

Related episodes:

• M&M #104: Benefits & Risks of UV Radiation & Sunlight, Skin Health, Vitamin D, Nitric Oxide, Evolution of Skin Color | Richard Weller
• M&M #146: Photobiology, Sunlight, Firelight, Incandescent Bulbs vs. LEDs, Mitochondria, Melatonin, Sunscreen & the Optics of the Body | Scott Zimmerman

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About the guest: Joshua Siegel, MD, PhD is a psychiatrist & systems neuroscience at New York University. He uses functional imaging to study the effects of psychedelics and other drugs on the human brain.

Episode summary: Nick and Dr. Siegel discuss: fMRI and how it works; relationship between neural activity and blood flow; functional connectivity & the default mode network of the human brain; the functional effects of psilocybin on the brain; the role that subjective & expectancy effects in psychedelics medicine; and more.

Related episodes:

• M&M #173: Psychedelics, Consciousness, Psychiatry, Psychology, Mental Health & the Entropic Brain Hypothesis
• M&M #163: Anesthesia, Placebo Effects, Consciousness, Subjectivity, MDMA, Ketamine, Opioids, Psychedelics

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About the guest: Richard Cytowic is a neurologist, poplar science writer and professor at the George Washington University.

Episode summary: Nick and Dr. Cytowic discuss: the effects of smart phones and social media on the developing and adult brain; artificial blue light vs. broad spectrum natural light; attention & addiction to technology; sensory overstimulation & “virtual autism”; synesthesia and multimodal sensory perception; and more.

Related episodes:

• M&M 78: Nature vs. Nurture, Neurogenetics, Personality, Autism, Schizophrenia, Synesthesia, Perception, Agency & Free Will | Kevin Mitchell

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About the guest: Thomas Weimbs, PhD is a biologist at UC-Santa Barbara whose lab studies kidney function in health and disease.

Episode summary: Nick and Dr. Weimbs discuss: basic kidney biology; kidney stones and their causes, including dietary oxalates and fructose; the kidney damaging effects of common pharmaceuticals like Ibuprofen; the beneficial effects of BHB and ketosis for kidney health; the myth that high protein intake is bad for the kidney; kidney diseases and their causes; and more.

Full version available on Substack and YouTube.

Related episodes:

• M&M 158: Ketosis & Ketogenic Diet: Brain & Mental Health, Metabolism, Diet & Exercise, Cancer, Diabetes | Dominic D'Agostino
• M&M #139: Metabolic Switching, Fasting, Ketosis, Neuroplasticity, Diet & Neurodegenerative Disease | Mark Mattson

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About the guest: Nick Norwitz, PhD received his PhD in Physiology at Oxford University and is finishing his MD degree at Harvard Medical School. He is also an independent content creator focused on making metabolic health mainstream.

Episode summary: Nick and Dr. Norwitz discuss: blood lipids & cholesterol; high cholesterol levels and what they can mean for different people; the “lean mass hyper-responder” phenotype to carb restriction; ketogenic & carnivore diets; public trust in medical & science institutions; n=1 (“n of one”) science experiments; and more.

Related episodes:

• M&M 158: Ketosis & Ketogenic Diet: Brain & Mental Health, Metabolism, Diet & Exercise, Cancer, Diabetes | Dominic D'Agostino
• M&M 192: Seed Oils, Chronic Disease, Diet & Religious Cults, Mainstream Medicine vs. Independent Research | Tucker Goodrich

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About the guest: Nicole Avena, PhD is a neuroscientist at Mount Sinai. She studies the effects of sugar and diet on animal behavior and the brain. She is also the author of, “Sugarless.”

Episode summary: Nick and Dr. Avena discuss: drug addiction vs. food addiction; glucose, fructose & artificial sweeteners; the extent to which sugar consumption can drive dependency & withdrawal; fructose metabolism & live health; sweetness & palatability; ultra-processed foods; and more.

Related episodes:

• M&M 140: Obesogens, Oxidative Stress, Dietary Sugars & Fats, Statins, Diabetes & the True Causes of Metabolic Dysfunction & Chronic Disease | Robert Lustig
• M&M #134: Omega-6-9 Fats, Vegetable & Seed Oils, Sugar, Processed Food, Metabolic Health & Dietary Origins of Chronic Inflammatory Disease | Artemis Simopoulos | #134

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About the guest: Angel Nadal, PhD is a biologist in Spain whose lab studies endocrine disruptors (e.g. microplastics), hormones (estrogen, insulin), and the endocrine functions of the pancreas in health & disease.

Episode summary: Nick and Dr. Nadal discuss: endocrine biology of the pancreas; insulin and estrogen signaling in the pancreas; BPA, microplastics, and other xenoestrogens; pregnancy & fetal development; effects of hormone disruptors in males vs. females; and more.

Related episodes:

• M&M 145: Epigenetics, Hormones, Endocrine Disruptors, Microplastics, Xenoestrogens, Obesogens & Obesity, Inheritance of Acquired Characteristics | Bruce Blumberg
• M&M #124: Hormonal Contraception, Sex Hormones, Menstruation, Pregnancy, Puberty, Estrogens, Androgens, Effects of Birth Control on Cognition | Adriene Beltz

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About the guest: Gary Churchill, PhD is a statistician & geneticist at the Jackson Research laboratory in Maine. His lab uses a systems approach to investigate the genetics of complex biological traits in health & disease.

Episode summary: Nick and Dr. Churchill discuss: his recent papers looking at the effects of caloric restriction & intermittent fasting on nearly 1,000 genetically diverse mice; how dietary restrictions affect longevity, metabolic health, immunity, and hundreds of biomarkers; the role of genetics vs. diet in aging; and more.

Related episodes:

• M&M #139: Metabolic Switching, Fasting, Ketosis, Neuroplasticity, Diet & Neurodegenerative Disease

This content is never meant to serve as medical advice.
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About the guest: Ev Fedorenko is a neuroscientist at MIT. He lab studies the neural basis of language, speech, and thought in the human brain.

Episode summary: Nick and Dr. Fedorenko discuss: the relationship between language and thought; the extent to which language is for thinking vs. communication; Noam Chomsky’s Universal Grammar theory; Sapir-Whorf hypothesis; language acquisition & language learning; language networks in the brain; neuroanatomy & brain lateralization; large language models (LLMs) & machine intelligence; and more.

Related episodes:

• M&M #141: Evolution, Language, Domestication, Symbolic Cognition, AI & Large Language Models
• M&M #20: Language, Symbolic Cognition, Evolution, Origins of the Human Mind | Terrence Deacon

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About the guest: Nir Lipsman, MD, PhD is a neurosurgeon and neuroscientist at the University of Toronto.

Episode summary: Nick and Dr. Lipsman discuss: neurosurgery; the blood-brain barrier and how it works; using focused ultrasound technology to non-invasively treat patients; regulatory impediments to clinical research; costs, constraints, and future applications of ultrasound tech for treating psychiatric conditions; and more.

Related episodes:

• M&M #168: Sleep: Neural Circuits, Orexin/Hypocretin, Hypothalamus, Neuromodulators, Stress & Cortisol, Sleep Drugs & Ultrasound Technology | Luis de Lecea
• M&M #147: Ketamine: Opioid System, Sex Differences, S- vs. R- Isomers, Depression & Ultrasound Imaging Technology | Tommaso Di Ianni

*This content is never meant to serve as medical advice.

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About the guest: Marcelo Dietrich, MD, PhD is an associate professor in Comparative Medicine & Neuroscience at Yale University, where his lab studies the neural basis of behavior in mammals.

Episode summary: Nick and Dr. Dietrich discuss: maternal care behavior, mother-infant bonding, and feeding in infant mammals; neural circuits regulating hunger & satiety; brain development & early social learning; behavioral variability among individuals; and more.

Related episodes:

• M&M #159: Neuroscience of Social Behavior, Pain, Empathy, Emotion, Brain Mechanisms of MDMA | Monique Smith
• M&M #108: Monogamy, Sexual & Parental Behavior, Social Attachment, Oxytocin, Sex Hormones, Childhood Psychosis, Menopause & Brain Development | Devanand Manoli

*This content is never meant to serve as medical advice.

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About the guest: Maxime Aubert, PhD is a geochemist & archeologist at Griffiths University in Australia. He specializes in the application of advanced analytical techniques to date the age of ancient rock art and hominin fossils.

Episode summary: Nick and Dr. Aubert discuss: the oldest known cave art and what it depicts; human evolution & interbreeding with different human sub-species; the origins of anatomically modern humans & advanced cognition; and more.

Related episodes:

• M&M #126: Evolution of Human Behavior, Anatomy & Diet, Homo naledi & the Cave of Bones | John Hawks
• M&M #38: Human Evolution, Homo Naledi, Ancient Drug Use, Ritual Burials, Origins of the Human Mind | Lee Berger

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About the guest: Nick Jikomes, PhD is the creator and host of the podcast. You can read more about him here.

Episode summary: Nick answers questions from listeners are topics such as: his scientific background & interests; staying up-to-date on research & selecting guests; thoughts on psychedelic science & drug use; questions related to diet, metabolic health & fat loss; controversial ideas worth considering; and more.

*This content is never meant to serve as medical advice.

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About the guest: June Round, PhD is a microbiologist whose lab at the University of Utah studies microbiome-host interactions, gut microbiota, immunity, metabolism, obesity, and other disorders.

Episode summary: Nick and Dr. Round discuss: how the immune system and gut microbiome interact; dietary fiber & short-chain fatty acid production by gut microbes; nutrient absorption; obesity & metabolic syndrome; type I diabetes; cleanliness, development & the “hygiene hypothesis”; and more.

Related episodes:

• M&M #133: Infant Microbiome & Breast Milk, Oral Microbiome & Cavities, Gut Health, Fiber, Probiotics, Diet, Sex Hormones, Soy Foods & Estrogens | Carolina Tropini
• M&M #103: Connections Between Microbiome, Exercise, Diet, Metabolism, Circadian Rhythms, Endocannabinoids & Health | Christoph Thaiss

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About the guest: Gregory Scherrer, PharmD, PhD is a neuroscientist whose lab at the University of North Carolina studies the neural basis of pain, including its sensory, emotional, and cognitive components.

Episode summary: Nick and Dr. Scherrer discuss: the neural basis of pain sensation & pain perception; opioids & the opioid system; cognitive modulation of painful experiences; neural basis of placebo effects; endogenous opioid system; and more.

Related episodes:

• M&M #52: Pain Drugs, NSAIDs, Opioids, Oxycodone, Heroin, Fentanyl & the Neuroscience of Pain | David Roberson
• M&M #159: Neuroscience of Social Behavior, Pain, Empathy, Emotion, Brain Mechanisms of MDMA | Monique Smith

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Special episode: Episodes in the Independent Scholars (IS) series are available in full to paid subscribers on the M&M Substack. This is a free, partial version.

About the guest: Steven Rofrano became interested in human health & food, including ancestral vs. modern diets, from personal experiences in diet & allergies during college. He is co-founder and CEO at Ancient Crunch, Inc., which provides alternatives to widely consumed ultra-processed snack foods. Before becoming an entrepreneur Steven studied mathematics at Yale University and worked as a software engineer.

Episode summary: Nick and Steven discuss: ancestral vs. modern foods; seed oils & polyunsaturated fatty acids (PUFAs); inflammation, allergies, and immunity; PUFAs, free radicals, and oxidative stress; the corrupting influence of private industry on food science; the history of seed oils; animal vs. plant fats; Steven’s food startup; and more.

Related episodes:

• M&M #176: Bad Science, Nutrition Epidemiology, History of Obesity Research, Diet & Metabolic Health | Gary Taubes
• M&M #136: Seed Oils, Omega-6 PUFAs, Inflammation, Obesity, Diabetes, Chronic Disease & Metabolic Dysfunction | Chris Knobbe

*This content is never meant to serve as medical advice.

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About the guest: Gary Taubes is a researcher, science historian, and science journalist. He has written several books, including “Rethinking Diabetes.”

Episode summary: Nick and Gary Taubes discuss: the field of nutrition epidemiology and why it’s filled with so much junk science; social factors influencing scientific research; the history of obesity & diabetes research; the energy balance vs. carbohydrate-insulin models of obesity; fats, carbs & insulin resistance; and more.

Related episodes:

• Obesogens, Oxidative Stress, Dietary Sugars & Fats, Statins, Diabetes & the True Causes of Metabolic Dysfunction & Chronic Disease | Robert Lustig | #140
• Obesity Epidemic, Diet, Metabolism, Saturated Fat vs. PUFAs, Energy Expenditure, Weight Gain & Feeding Behavior | John Speakman | #132

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About the guest: Austin Argentieri, PhD is a researcher in the Analytic & Translational Genetics Unit at the Massachusetts General Hospital with academic appointments at Harvard & the Broad Institute. His research focuses on large-scale analyses to to understand human aging.

Episode summary: Nick and Dr. Argentieri discuss: chronological vs. biological age; DNA methylation and aging clocks; proteomics and protein measurements in aging research; health, longevity, and human healthspan; and more.

Related episodes:

• Aging, mTOR, Sirtuins, Rapamycin, Metformin, the Truth of Resveratrol & Longevity Supplements, David Sinclair & Anti-Aging Myths | Matt Kaeberlein | #151
• Cellular Aging, Taurine, Nutrition, Senescence, Longevity, Mitochondria, Metabolism | Vijay Yadav | #122

*This content is never meant to serve as medical advice.

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About the guest: Sean Hartig, PhD is an associate professor at the Baylor College of Medicine, where is lab studies adipose (fat) tissue, metabolic regulation, and obesity & energy balance disorders.

Episode summary: Nick and Dr. Hartig discuss: visceral vs. subcutaneous fat; white, brown, and beige adipose tissue; physiology of fat cells; obesity, insulin resistance, and leptin resistance; hormones & fertility; GLP-1 drugs for weight loss; and more.

Related episodes:

• Obesogens, Oxidative Stress, Dietary Sugars & Fats, Statins, Diabetes & the True Causes of Metabolic Dysfunction & Chronic Disease | Robert Lustig | #140
• GLP-1, Weight Loss Drugs, Ozempic, Obesity, NMDA Receptors, Metabolism & Brain Health | Christoffer Clemmensen | #161

*This content is never meant to serve as medical advice.

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About the guest: Robin Carhart-Harris, PhD is a neuroscientist & psychopharmacologist. His lab at the University of California-San Francisco studies the effects of psychedelics and other drugs on the human brain, using neuroimaging and other approaches.

Episode summary: Nick and Dr. Carhart-Harris discuss: psychedelics & the human brain; functional connectivity & entropy in brain patterns; the “entropic brain” hypothesis of psychedelic drug action; psychiatry & depression; psychology, Carl Jung & Sigmund Freud; the FDA’s rejection of MDMA-assisted psychotherapy for PTSD; latest research on psychedelics; and more.

Related episodes:

• Anesthesia, Placebo Effects, Consciousness, Subjectivity, MDMA, Ketamine, Opioids, Psychedelics | Boris Heifets | #163
• DMT, Serotonin, Inflammation, Psychedelics, and Past, Present & Future of Psychedelic Medicine | David & Charles Nichols | #137

*This content is never meant to serve as medical advice.\

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About the guest: Caetano Reis e Sousa, DPhil is an immunologist and Principal Group Leader at the Francis Crick Institute in London. His lab studies immune system function, including its ability to fight infection and cancer.

Episode summary: Nick and Dr. Reis e Sousa discuss: dendritic cells & innate immunity; how the immune system recognizes pathogens, damaged cells, and cancer cells; gut microbiome & non-pathogenic bacteria; inflammation; vitamin D & gut-immune interactions; cancer; and more.

Related episodes:

• Ketogenic Diet, Cancer, Microbiome, Nutrition & the Immune System | Maayan Levy | #72
• Microbiome-Gut-Brain Axis in Health & Disease | John Cryan | #63

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About the guest: Robert Barton, PhD is an evolutionary anthropologist and Professor at Durham University. He studies the evolution of the brain and behavior across species, including humans.

Episode summary: Nick and Dr. Barton discuss: mammalian brain evolution; how brain and body size scale across mammals; how metabolism relates to brain size and function; the evolution of the neocortex & cerebellum in primates & humans; the concept of “intelligence” and whether it relates to brain size; and more.

Related episodes:

• Evolution of Complex Behavior, Perception, Cognition, Consciousness & the Brain | Paul Cisek | #107
• Organisms, Cities, Companies & the Science of Scale | Geoffrey West | #12

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About the guest: Melissa Herman, PhD is a neuroscientist and associate professor at the University of North Carolina. Her lab studies the effects of drugs on the brain and behavior in rodents.

Episode summary: Nick and Dr. Herman discuss: sex differences in the brain between males and females; behavioral variability among individuals; the effects of psychedelics like psilocybin on the amygdala and hypothalamus; effects of alcohol and vaporized nicotine; and more.

Related episodes:

• Drug Addiction, Cocaine, Nicotine, Caffeine, Amphetamines, Opioids, THC & Neuroscience | Christian Lüscher | #40
• Sex Differences in the Brain, Endocannabinoid Biology, Purpose of Juvenile Play Behavior, Cannabis & Pregnancy | Margaret McCarthy | #81

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About the guest: Giulia Santoni, PhD is a neuroscientist who obtained her PhD at the EPFL in Switzerland, where she studied epigenetic influences on memory formation.

Episode summary: Nick and Dr. Santoni discuss: transcription & gene regulation; synaptic plasticity; learning & associative memory; epigenetics, histones, DNA methylation, and mechanisms of gene regulation; chromatin plasticity & the neural basis of memory formation; and more.

Related episodes:

• Emotion, Cognition, Consciousness, Behavior & Brain Evolution | Joseph LeDoux | #73
• Cognitive Neuroscience, Cognitive Flexibility & Control, Attention, Working Memory, Multitasking & Behavior | Tobias Egner | #130

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About the guest: Luis de Lecea, PhD is a neurobiologist whose lab at Stanford University studies the neural basis of sleep & wakefulness in animals.

Episode summary: Nick and Dr. de Lecea discuss: the neural basis of sleep; sleep architecture & sleep phases (NREM vs. REM sleep); orexin/hypocretin neurons & the lateral hypothalamus; cortisol & stress; circadian rhythms; neuromodulators (norepinephrine, dopamine, etc); sleep across animal species; sleep drugs; ultrasound technology; and more.

Related episodes:

• Sleep, Dreaming, Deep Neural Networks, Machine Learning & Artificial Intelligence, Overfitted Brain Hypothesis, Evolution of Fiction & Art | Erik Hoel | #43
• Consciousness, Anesthesia, Coma, Vegetative States, Sleep Pills (Ambien), Ketamine, AI & ChatGPT | Alex Proekt | #101

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About the guest: Iain Oswald, PhD is an organic chemist and Director of Research & Development at Abstrax Tech.

Episode summary: Nick and Dr. Oswald discuss: plant chemistry; marijuana strains and their aroma; the chemical basis of cannabis aroma; terpenes vs. non-terpene volatile organic compounds; and more.

Related episodes:

• Marijuana, Plant Chemistry, Terpenes, Volatile Sulfur Compounds, Cannabis Industry, What Pungent Weed Smells Like & Why | Iain Oswald | #114
• Endocannabinoids, Stress, Exercise, Cortisol, Anxiety, Cannabis & Effects of Marijuana on Brain Development | Matthew Hill | #123

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About the guest: Rudyard Lynch is a history and anthropology scholar and host of the popular YouTube channel, whatifalthist.

Episode summary: Nick and Rudyard discuss: history of agriculture, diet & food; population density, social structure, and social behavior; the rise and fall of civilizations; history and future of religion & spirituality; and more.

Related episodes:

• Organisms, Cities, Companies & the Science of Scale | Geoffrey West
• Psychedelics, Civilization, Religion, Death & Plant Medicine | Brian Muraresku

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About the guest: Michael Lynch, PhD is an evolutionary biologist at Arizona State University who studies the origins of genomic and cellular complexity.

Episode summary: Nick and Dr. Lynch discuss: natural selection vs. genetic drift; genetic mutations & the speed of evolution; origin of life; the evolution of cellular complexity; epigenetics & the inheritance of acquired characteristics; and more.

Related episodes:

• Evolution & Animal Development: How Nature Builds & Changes Bodies | Sean B. Carroll | #138
• Evolution, Language, Domestication, Symbolic Cognition, AI & Large Language Models | Terrence Deacon | #141

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About the guest: Richard Bazinet, PhD is neurochemist and nutritional scientist at the University of Toronto. His lab studies brain lipid metabolism in health and disease.

Episode summary: Nick and Dr. Bazinet discuss: lipid metabolism in the liver and brain; dietary fatty acids (saturated, monounsaturated, polyunsaturated); fatty acids in brain health & disease; endocannabinoids; omega-3 PUFAs, seed oils & diet; and more.

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About the guest: Tucker Goodrich is an independent researcher and self-described “seed oil zealot” who credits many of his own health improvements with minimizing his consumption of industrial seed oils. He runs a Substack page, and provides interesting commentary about scientific research on seed oils, metabolic health, and related topics.

Episode summary: Nick and Tucker discuss: what seed oils are and their history; differences between omega-6 and omega-3 polyunsaturated fatty acids (PUFAs); seed oils, sunburn, and oxidative stress; Seventh Day Adventism and the relationship between religion, ideology, and diet; paleobiology of human diet; and more.

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About the guest: Melissa Sharpe, PhD is a neuroscientist. Her lab at the University of Sydney studies reinforcement and reward learning in rodents.

Episode summary: Nick and Dr. Sharpe discuss: dopamine and its association with reward learning and motivation; reinforcement learning & the brain; the lateral hypothalamus and feeding behavior; and more.

Related episodes:

• Drugs, Addiction & Neuroplasticity: Psychedelics, MDMA, Opioids, Cocaine, Amphetamine (Adderall), Nicotine, Marijuana & Alcohol | Robert Malenka | #162
• Neuroscience of Pleasure, Reward, Liking vs. Wanting, Motivation, Food vs. Drug Addiction & Emotion | Kent Berridge | #94

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About the guest: Boris Heifets, MD, PhD is an anesthesiologist and researcher at Stanford University. His lab studies non-ordinary states of consciousness and psychoactive drugs like MDMA, ketamine, and psychedelics.

Episode summary: Nick and Dr. Heifets discuss: anesthesia and how anesthetics work; placebo effects & expectations in clinical research; ketamine as an antidepressant, anesthetic, and recreational drug; the subjective effects of psychedelics and other drugs; MDMA and Lykos Therapeutics’ attempts to gain FDA approval for MDMA-assisted psychotherapy; opioids & placebo effects; and more.

Related episodes:

• How Does Ketamine Work & Is It Addictive? | Christian Lüscher | #90
• Consciousness, Anesthesia, Coma, Vegetative States, Sleep Pills (Ambien), Ketamine, AI & ChatGPT | Alex Proekt | #101

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About the guest: Robert Malenka, MD, PhD is psychiatrist & neuroscientist. He has spent most of his career at Stanford University, where his lab studies synaptic plasticity, mechanisms of drug action in the brain, and the neural basis of behavior.

Episode summary: Nick and Dr. Malenka discuss: mechanisms of synaptic plasticity in the brain, such as LTP & LTD; addiction & the dopamine reward circuitry of the brain; psychoactive drugs ranging from stimulants (cocaine, nicotine, amphetamines) to opioids (fentanyl), psychedelics, MDMA, THC, and alcohol; and more.

Related episodes:

• How Does Ketamine Work & Is It Addictive? | Christian Lüscher | #90
• Neuroscience of Social Behavior, Pain, Empathy, Emotion, Brain Mechanisms of MDMA | Monique Smith | #159

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About the guest: Christoffer Clemmensen, PhD is scientist running the Metabolism & Molecular Pharmacology group at the University of Copenhagen in Denmark. His lab studies the biological basis of obesity & other metabolic disorders.

Episode summary: Nick and Dr. Clemmensen discuss: GLP-1 & gut hormones; obesity & metabolic disease; GLP-1 agonists and weight loss drugs (e.g. Ozempic); novel, dual-action weight loss drugs his lab has created; and more.

Previous discussion: Metabolism, Obesity & Psychedelics for Metabolic Disease | Christoffer Clemmensen | #105

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About the guest: Eugene Morin, PhD is a Professor of Anthropology at the University of Trent who studies Paleolithic humans and animals.

Episode summary: Nick and Dr. Morin discuss evolution of Paleolithic humans; Neanderthal diet & cultural capacity; key human adaptations related to endurance and stamina; hunter gatherer hunting strategies; evolution of human digestion; and more.

*This content is never meant to serve as medical advice.

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About the guest: Monique Smith, PhD is an assistant professor of neurobiology at the University of California-San Diego, where her lab studies the neuroscience of social behavior, pain, and emotion.

Episode summary: Nick and Dr. Smith discuss: the neurobiology of pain perception; social & empathy-like behavior in animals; emotion; brain mechanisms of MDMA; serotonin; and more.

*This content is never meant to serve as medical advice.

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About the guest: Dominic D'Agostino, PhD is a researcher and professor at the University of South Florida, where his lab studies metabolism, human biology, and related subjects.

Episode summary: Nick and Dr. D'Agostino discuss: ketosis and the ketogenic diet; effects of ketosis on diabetes, insulin resistance & metabolic health; effects on brain & mental health; relationship with exercise performance; cholesterol, LDL, triglycerides & other biomarkers; cancer; and more.

*This content is never meant to serve as medical advice.

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About the guest: Robert Lufkin, MD is a radiologist and professor at UCLA. His new book is called, "Lies I Taught in Medical School."

Episode summary: Nick and Dr. Lufkin talk about: the history of medicine in the United States; diet & lifestyle vs. pharmaceuticals in acute vs. chronic disease; diabetes, metabolic syndrome & insulin resistance; health institutions like the American Diabetes Association & American Heart Association, including their financial influences; carbohydrates, fats, dietary cholesterol, ketosis, and related topics in metabolism; bloodwork & choosing the right doctor; and more.

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About the guest: Stephen Sideroff, PhD is a clinical psychologist and Associate Professor of Psychiatry and Behavioral Sciences at UCLA. His new book is, "The 9 Pillars of Resilience."

Episode summary: Nick and Dr. Sideroff discuss: childhood & developmental psychology; clinical & Gestalt psychology; stress & resilience; pharmaceuticals, talk therapy, and plant medicines; emotions & psychopathology; and more.

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About the guest: Andrew Dillin, PhD is Professoer of Molecular & Cell Biology at UC-Berkeley and Howard Hughes Medical Institute investigator. His lab studies mechanisms of aging, mitochondrial biology, and related subjects.

Episode summary: Nick and Dr. Dillin discuss: cell biology; mitochondria & the endoplasmic reticulum; aging & autophagy; mitochondrial biology in neurons; diet, exercise, and oxygen effects on mitochondrial health; and more.

*This content is never meant to serve as medical advice.

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About the guest: Eske Willerslev, PhD is an evolutionary biologist and Professor of evolution at both the University of Copenhagen and University of Cambridge.

Episode summary: Nick and Dr. Willerslev discuss: human evolution out of Africa; the origins of modern Europeans; hunter gatherers, early farmers, and pastoralists; genetics of human disease risk; evolution of diet & metabolism; evolution of light skin color; and more.

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About the guest: Georgia Ede, MD is a psychiatrist and author of, "Change Your Diet, Change Your Mind: A Powerful Plan to Improve Mood, Overcome Anxiety, And Protect Memory for a Lifetime of Optimal Mental Health."

Episode summary: Nick and Dr. Ede discuss: glucose vs. ketones for brain energy; metabolic health & insulin resistance; animal vs. plant-based foods; nutrients, anti-nutrients & plant toxins; ketogenic, carnivore & plant-based diets; carbohydrates & processed foods; treating bipolar disorder, schizophrenia & psychiatric illness with diet; and more.

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About the guest: Ryan Vandrey, PhD is a Professor of Psychiatry & Behavioral Sciences at Johns Hopkins University, where his lab studies the behavioral pharmacology of cannabis (marijuana), nicotine/tobacco, and other substances.

Episode summary: Nick and Dr. Vandrey discuss: marijuana; cannabinoids like THC; terpenes like limonene, myrcene, and pinene; the entourage effect; anxiety and other side effects of cannabis consumption; and more.

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About the guest: Matt Kaeberlein, PhD is a Professor of at the University of Washington and CEO of OptiSpan. His research focuses on the biology of aging and longevity.

Episode summary: Nick and Dr. Kaeberlein discuss: the biology of aging; mTOR, FGF1, growth & metabolism; sirtuins, NAD & NMN; longevity drugs like metformin & rapamycin; facts & myths about longevity molecules like resveratrol & taurine; controversies in aging research related to prominent Harvard researcher David Sinclair; epigenetic clocks; healthspan & lifespan; and more.

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About the guest: Mark Bear, PhD is a Professor of Neuroscience at MIT, where his lab studies the visual system, neuroplasticity, and the pathophysiology of amblyopia and visual impairments.

Episode summary: Nick and Dr. Bear discuss: the visual system in the brain, from the retina to visual cortex; critical periods of brain development; mechanisms of neuroplasticity; metaplasticity; amblyopia and visual impairments; ketamine & psychedelics; and more.

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About the guest: Kevin McKernan is the Chief Science Officer at Medicinal genomics and has been working the the biotechnology sector and conducting genomics research going back to his involvement in the Human Genome Project.

Episode summary: Nick and Kevin discuss: basics of DNA and RNA biology; mRNA vaccines and how they work compared to traditional vaccines; the mRNA vaccine manufacturing process; DNA contamination in the Pfizer and Modern mRNA vaccines for COVID; the SARS-CoV-2 spike protein; vaccine side effects; ivermectin and hydroxychloroquine; and more.

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About the guest: Luc van Loon, PhD is a Professor of Physiology of Exercise and Nutrition and Head of the M3-research group at the Department of Human Biology at Maastricht University. His lab focuses on the skeletal muscle adaptive response to physical (in)activity, the impact of nutrition on metabolism, and related topics.

Episode summary: Nick and Dr. van Loon discuss: amino acid biology; branched chain amino acids like leucine; atypical amino acids like taurine; muscle growth & muscle biology; dietary protein and plant vs. animal protein sources; resistance training and anabolic growth; the limits of dietary protein on muscle growth; and more.

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About the guest: Tommaso Di Ianni, PhD is an Assistant Professor in the Departments of Psychiatry & Behavioral Sciences and Radiology & Biomedical Imaging at the University of California, San Francisco. His lab uses ultrasound technology and deep learning to study the brain.

Episode summary: Nick and Dr. Di Ianni discuss: the current state of scientific understanding of ketamine; S-ketamine vs. R-ketamine isomers; the antidepressant effects of ketamine; ketamine's known mechanisms of action; sex-dependent effects of ketamine action in the brain; involvement of the opioid system in ketamine's effects; addiction; and more.

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About the guest: Scott Zimmerman is an optical engineer and photobiology expert

Episode summary: Nick and Scott talk about: how light interacts with the body and affects our cells; melatonin as an antioxidant; how red & near-infrared light affect mitochondria; sunlight, fire light, and artificial light; incandescent light bulbs vs. LEDs; negative health effects of artificial light; sunscreen & makeup; red & near-infrared light therapy; the optical properties of the human body; and more.

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About the Guest: Bruce Blumberg, PhD is a Professor of Cell & Developmental Biology at UC-Irvine. HIs lab studies epigenetics, gene x environment interactions, hormones & endocrine disruptors, obesogens & environmental toxins, and more.

Episode Summary: Nick and Dr. Blumberg discuss: Embryonic development; hormones and hormone receptors; estrogen & xenoestrogens; environmental toxins, obesogens, pesticides & contaminants; environmental causes of obesity; microplastics; how to avoid toxins in food & drinking water; and more.

*This content is never meant to serve as medical advice.

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About the Guest: Clare Bryant, DVM is a Professor of Innate Immunity at Cambridge University. Her lab studies the innate immune system, pathogen detection, inflammation, and chronic disease.

Episode Summary: Nick and Dr. Bryant discuss: mechanisms of inflammation; inflammasomes & fatty acids; infection & disease; innate vs. adaptive immunity; chronic inflammation; allergies & allergens; the evolution of the immune system; anti-inflammatory effects of fasting; and more.

*This content is never meant to serve as medical advice.

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Dr. Guillaume (Will) de Lartigue is a neuroscientist at the Monell Chemical Senses Center. His lab studies the neurobiology of eating, including how the vagus nerve senses internal stimuli in the gut. They discuss: gut-brain communication; the vagus nerve; gut hormones like leptin & GLP-1; weight loss drugs like Ozempic; glucose vs. fructose vs. non-caloric sweeteners; how the vagus nerve connects the gut to the dopamine reward system in the brain; the sensation of fats and sugars in the gut; food addiction & obesity; and more.

More M&M content about diet & metabolism: https://substack.com/search/diet%20metabolism?focusedPublicationId=513528&searching=focused_posts

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Dr. Nicolas Glynos received his PhD in Molecular & Integrative Physiology from the University of Michigan, where he studied the psychedelic drug DMT in the mammalian brain. They discuss: the history of DMT research; the use of DMT in ayahuasca; whether DMT is found endogenously in animals; why plants produce DMT; pineal gland, DMT & melatonin; the latest research looking at the presence and effects of DMT in the brain; and more.

More M&M content about psychedelics: https://substack.com/search/psychedelics?focusedPublicationId=513528&searching=focused_posts

psychedelics #DMT #science #neuroscience #podcast #serotonin

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About the Guest: Terrence Deacon, PhD is a Professor in the department of Anthropology at UC-Berkeley. He has written many papers and multiple books about the evolution of human language, origins of consciousness, and related topics.

Episode Summary: Nick and Dr. Deacon discuss various aspects of biological evolution, from natural vs. sexual selection to gene duplication and the consequences of domestication; the domestication of dogs and songbirds; human vs. non-human forms of vocal communication; ritual behavior & the origins symbolic cognition; artificial intelligence & large language models (LLMs); and more.

*This content is never meant to serve as medical advice.

language #consciousness #evolution #biology #AI #artificialintelligence #cognition #anthropology

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About the guest: Robert Lustig, MD is a physician-researcher and expert of metabolic health. He is Professor emeritus of Pediatrics, Division of Endocrinology at the University of California, San Francisco (UCSF), specializing in neuroendocrinology with an emphasis on the regulation of energy balance by the central nervous system. His research and clinical practice has focused on childhood obesity and diabetes.

Episode summary: Nick and Dr. Lustig discuss the true causes of obesity and metabolic discussion; how the in utero environment during pregnancy leads to multigenerational effects on health; different forms of sugar like fructose vs. glucose; different dietary fats like omega-6 and omega-3 PUFAs, and saturated fat; oxidative stress & mitochondria biology; how temperature, altitude & oxygen affect obesity; processed foods and how industry influences public perception; body positivity & public education; insulin, diabetes & fatty liver disease; statins & cardiovascular health; and more.

*This content is never meant to serve as medical advice.

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Mark Mattson, PhD is a semi-retired neuroscientist at Johns Hopkins who ran a research lab at the NIH for many years. He wrote the book, "The Intermittent Fasting Revolution." Nick and Dr. Mattson discussed: intermittent fasting & diet; ketosis & metabolic switching; aging & neurodegenerative disease; exercise, stress, and neuroplasticity; and more.

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Sean B. Carroll, PhD is an evolutionary developmental biologist at the University of Maryland, who recently stepped down as VP of Education at the Howard Hughes Medical Institute. He is the author of many popular science books, such as "Endless Forms Most Beautiful." They discuss: developmental biology & genetics; evolutionary biology; genetics, genome size & genetic mutation; animal diversity; snake venom; human brain evolution; and more.

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Dr. David Nichols is a retired chemist and father of Dr. Charles Nichols, a researcher studying psychedelics at Louisiana State University. They discussed: the history of psychedelics science from the 1970s to the present; DMT & 5-MeO-DMT; serotonin, inflammation, and psychedelics & anti-inflammatory drugs; psilocybin, ketamine, and other psychoactive drugs; and more

More M&M content about psychedelic science: https://substack.com/search/psychedelics?focusedPublicationId=513528&searching=focused_posts

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Dr. Chris Knobbe is a physician, diet & nutrition researchers, and author of, "The Ancestral Diet Revolution." He discusses: seed oils & their health consequences; different types of seed oils (soybean, corn, sunflower, etc.); omega-6 fats like linoleic acid; fatty acid metabolism and oxidation; obesity, diabetes & metabolic health; processed foods vs. whole foods; mitochondria & oxidative stress; and more.

Click here for more M&M content about diet & metabolism: https://substack.com/search/diet%20metabolism?focusedPublicationId=513528&searching=focused_posts

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Dr. Orrin Devinsky is a neurologist and Professor at the New York University School of Medicine. They discuss: dietary consumption trends in the US; processed vs. whole foods; vegetable oils & polyunsaturated fats; relationship between saturated fat, dietary cholesterol & heart disease; history of medicine in the US; obesity & diabetes; sugars, fructose, and metabolic health; ketogenic diet & ketosis; whether or not we can trust our public health institutions; and more.

More M&M content on diet & metabolism: https://substack.com/search/diet%20metabolism?focusedPublicationId=513528&searching=focused_posts

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Dr. Artemis Simopoulos is a physician and researcher specializing in endocrinology, nutrition, and metabolic health. They discuss: traditional hunter-gatherer diets vs. modern Western diets; dietary fats; omega-6 and omega-3 polyunsaturated fats; sucrose & sugar; chronic inflammatory diseases, obesity & diabetes; vegetable & seed oils vs. other cooking oils; processed foods; fish oil supplements; and more.

More content on the science of diet & metabolic health: https://substack.com/search/diet%20metabolism?focusedPublicationId=513528&searching=focused_posts

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Dr. Carolina Tropini is an assistant professor of Microbiology & Immunology at the University of British Columbia, where her lab studies the microbiome in health & disease. Topics covered: infant & vaginal microbiome, breast milk nutrients & C-sections vs. natural births; oral microbiome & cavities; gut microbiome & irritable bowel disease (IBD); fiber, short-chain fatty acids & probiotics; how gut bacteria influence sex hormones (estrogen, testosterone) in the body; and more.

More content about the microbiome: https://substack.com/search/microbiome?focusedPublicationId=513528&searching=focused_posts

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Dr. John Speakman is a biologist whose research focuses on energy balance, energy expenditure, genetic and environmental drivers of obesity and the energetic contribution to aging. They discuss: the history of the obesity epidemic in the US vs. China; changes in patterns of physical activity, diet, and energy expenditure in humans over time; how saturated fats vs. PUFAs affect basal metabolism; the relative contributions of fats, carbs, and protein to fat & weight gain; and more.

See this content to learn more about diet & metabolism: https://substack.com/search/diet%20metabolism?focusedPublicationId=513528&searching=focused_posts

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Nick talks to Dr. Ronald Krauss, a physician and researcher at UCSF who studies the relationship between diet & cardiometabolic health. They discuss: saturated vs. unsaturated fats; carbohydrates & fat synthesis; "good" vs. "bad" cholesterol; official US dietary guidelines and how they're established; funding of research by the food industry; and more.

More content on the science of diet & metabolic health: https://substack.com/search/diet%20metabolism?focusedPublicationId=513528&searching=focused_posts

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Dr. Tobias Egner is a Professor of Psychology & Neuroscience at Duke University, where his lab studies cognition, working memory, and cognitive control & flexibility. They discuss: what cognition is and how it's studied experimentally; working memory & attention; cognitive flexibility, cognitive control & multitasking; memory, perception, and predictive coding; and more.

To learn more about neuroscience, check out this content: https://substack.com/search/neuroscience?focusedPublicationId=513528&searching=focused_posts

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Dr. David Puts is a biological anthropologist at the Penn State University. His research focuses on the evolution and development of human sexuality and sex differences. They discuss: the biological basis of sex; gametes, sex chromosomes & sex hormones; the development of sexual orientation; the evolution of sexual dimorphism & behavior in primates; monogamy & polygyny; and more.

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Dr. Moses Chao is a professor at the New York University School of Medicine. His lab studies how the environment, neuronal activity, inflammation, injury and disease affect the nervous system. They discuss topics related to his new book, "Peripheral: How Your Nervous System Predicts and Protects Against Disease." Topics include: how the peripheral nervous system differs from the central nervous system; the enteric nervous system & gut health; pain sensation; exercise & neuroplasticity; neurodegenerative disease; and more.

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Mikael Palner, PhD is a neuroscientist at the University of Souther Denmark. His lab studies the neuronal circuits involved in obsessive compulsive disorder and anxiety . They investigate the effects of serotonergic psychedelic and non-psychedelic drugs that increase neuronal plasticity. They discuss: psychedelics & the brain; the neuroscience of stress, anxiety & compulsive behavior; microdosing psilocybin; and more.

More psychedelic science content: https://substack.com/search/psychedelics?searching=focused_posts&focusedPublicationId=513528

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Dr. John Hawks is a paleoanthropologist and professor of anthropology at the University of Wisconsin-Madison. They discuss: the evolution of human behavior, diet, anatomy, and culture; Neanderthals, Denisovans, Homo erectus, and other species; the latest discoveries related to Homo naledi, which was the subject of the Netflix documentary, "Cave of Bones."

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Dr. Mario Capecchi is a professor of genetics at the University of Utah & Nobel laureate. He discussed: his latest work in neurobiology, looking at the role of microglia in anxiety & Obsessive Compulsive Disorder (OCD); his Nobel Prize-winning work in molecular genetics; molecular biology & genetics; his childhood experiences as an orphan in Italy during World War II; immigrating to the US; his education & scientific career; his exercise & diet; advice for aspiring scientists; and more.

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Dr. Adriene Beltz is an associated professor of psychology at the University of Michigan who studies the effects of sex hormones & hormonal contraception on human cognition and the brain. They discuss: sex hormones (androgens & estrogens); hormonal regulation of menstruation, puberty, and pregnancy; common forms of hormonal birth control & how they work; effects of sex hormones & hormonal birth control on cognition & the brain; and more.

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Nick talks to Dr. Matthew Hill, a neuroscientist at the University of Calgary whose lab studies how the endocannabinoid system and cannabis (marijuana) influence the brain & behavior. They discuss: endocannabinoid biology; endocannabinoid regulation of stress & anxiety; endocannabinoids & exercise; how marijuana & THC influence brain development; and more.

See previous episode with Dr. Matthew Hill: https://mindandmatter.substack.com/p/matthew-hill-endocannabinoid-system-8ff#details

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Nick talks to molecular physiologist Dr. Vijay Nadav, an assistant professor at Columbia University whose lab studies the molecular & cell biology of aging, nutrition, and longevity. They discuss: the cell biology of aging; how nutrients affect aging & disease; the atypical amino acid taurine & its effects on aging; taurine clinical trials & supplementation; diet, nutrition & anti-aging effects; and more.

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Nick talks to Gül Dölen, MD, PhD. is a neuroscientist at Johns Hopkins University whose lab studies social behavior, synaptic plasticity, psychedelics & evolution. They discuss: What drugs like LSD, psilocybin, ketamine, MDMA, and ibogaine have in common in terms of their molecular effects in the brain; why Dr. Gül Dölen believes all of these drugs can be described as "psychedelics"; the relationship between psychedelics and neuroplasticity vs. metaplasticity; how addictive drugs are similar to and different from psychedelics; social reward learning in rodents & critical periods of plasticity; the subjective effects of psychedelics; novel psychedelic drug development; human social behavior, mental health, and psychiatry; and more.

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Nick talks to Dr. Alan Davis, a clinical psychologist and Director of the Center for Psychedelic Drug Research & Education at Ohio State University. They discuss: the effectiveness of mainstream forms of psychotherapy and antidepressant medications (SSRIs) for depression; psychedelic medicine & psilocybin-assisted psychotherapy; the relevance of the subjective effects of psychedelics for their therapeutic effects; FDA approval for MDMA- and psilocybin-assisted psychotherapy in the coming years; and more.

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Nick talks to Bryan Roth, MD, PhD, a Professor of Pharmacology at the University of North Carolina. Dr. Roth has been studying the molecular mechanisms of psychedelics since the 1980s. They discuss: serotonin 2A receptors in the mammalian brain; psychedelics & neuroplasticity; classic psychedelics (e.g. LSD, psilocybin, DMT) compared to drugs like ketamine & MDMA; TrkB receptors & BDNF; engineering novel drugs & psychiatric treatment methods; latest findings in psychedelic science.

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Nick talks to ethnopharmacologist Dr. Dennis McKenna, who is the brother of psychonaut Terence McKenna and author of the book, "The Brotherhood of the Screaming Abyss." They discuss: the lives and psychedelic adventures of Dennis & Terence McKenna; experiences with psilocybin mushrooms & DMT; Carl Jung & psychology; the medical relevance of subjective psychedelic experiences; drugs, culture & society; and more.

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Nick talks to Daniel Karlin, MD, a board-certified physician in psychiatry, addiction medicine & clinical informatics who is the Chief Medical Officer at MindMed. They discuss: psychiatry; incentives in scientific & medical research; healthcare & mental health; psychedelics; LSD for anxiety; MDMA for autism; ibogaine derivatives for addiction; patient access & care; and more.

Try Everyday Dose, high-quality coffee & matcha alternatives with functional mushrooms & other supplements.

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Nick talks to chemist & food scientist Dr. Selina Wang about: food quality & purity; cooking oils (avocado, olive, vegetable, etc.); fruits & vegetables; oxidation & purity of cooking oils; how to identify high quality, pure foods to purchase; and more.

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Nick talks to Dr. Luc van Loon, Professor of Exercise Physiology & Nutrition at Maastricht University, about topics in exercise science, health & nutrition. They discuss: macronutrients & energy; protein quality & digestibility; endurance & resistance training; plant vs. animal protein; muscle conditioning & muscle fibers; sleep & aging; muscle physiology & metabolism; and more.

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Nick talks to Dr. Iain Oswald, who has a PhD in chemistry from the University of Texas-Dallas and is principal scientist Abstrax Tech, a cannabis research and product development company. He is an expert in using cutting edge analytical chemistry techniques to study plant chemistry and has done a lot of work to decipher the chemistry of commercial cannabis, including lesser-known compounds found in the essential oils of marijuana plants and how these relate the sensory qualities of marijuana.

They discuss: the aroma of cannabis & the chemical compounds that dictate different aspects of its aroma; consumer preferences when it comes to marijuana aroma; terpenes, which are volatile compounds abundant in the plant world; his research on volatile sulfur compounds, which are found in nature in things like garlic and the aerosols produced by skunks, and how lesser-known cannabis compounds in this chemical family relate to some of the pungent, gassy/skunky odors commonly associated with marijuana; his journey from academia into the private sector, and what’s on the horizon for cannabis research.

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Nick talks to board-certified toxicologist Dr. Echo Rufer. The conversation starts with a brief overview of what the science of toxicology is all about & a little bit about alcohol toxicity. They then discuss: differences between vaping and smoking; what toxins are produced through the combustion of plant material, especially tobacco & marijuana; cannabinoids like THC & CBD, as well as cannabis terpenes; relationship between dose, method of consumption & toxicity of chemical compounds; causes of the vaping-associated pulmonary injury (VAPI) associated with the vitamin E acetate that was found in some illicit market cannabis vape products; best ways to minimize toxin exposure for people who inhale plant-based consumer products such as tobacco or nicotine products or marijuana.

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Nick talks to Dr. Nathan Price, who is a professor at the Institute of Systems Biology and Chief Science Officer of Thorne HealthTech. They discuss topics related to his new book, "The Age of Scientific Wellness: Why the Future of Medicine is Personalized, Data-Rich, and in Your Hands."

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Listen to Nick's previous discussion with Dr. Nathan Price:
[https://mindandmatter.substack.com/p/podcast-47-nathan-price-metabolism#details]

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Nick talks to Daniel Brady, PhD a neuroscientist who studied sensory systems in the developing brain. Dr. Brady is also the co-founder and CEO of Orita.ai, a startup using machine learning & AI to solve data problems for direct-to-consumer brands. They discuss: critical periods of learning, childhood brain development, neuroplasticity, synesthesia, language acquisition, Orita.ai, machine learning & AI, customer segmentation, data science, and more.

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Nick talks to Dr. Rusty Gage, a neurobiologist at the Salk Institute whose lab studies how genes & environment interact to influence brain development, including the process of adult neurogenesis. They discuss: what neurogenesis is and how it works; lifestyle factors that influence neurogenesis, such as exercise, intermittent fasting, etc.; molecular pathways involved in neurogenesis; depression & PTSD; memory formation and the function of newly born adult neurons; and more.

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Nick talks with Nick Mosley, who is CEO of a cannabis testing lab called Confidence Analytics, which conducts analytical testing for legal cannabis products in Washington & California. They discuss: how analytical testing for cannabis products works; THC, CBD, and cannabinoid content; terpenes; pesticides, heavy metals, and microbial contaminants; the phenomenon of THC inflation & lab shopping in the legal marijuana industry; how consumers can discern whether cannabis products are safe & consistent.

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What is Mind & Matter?

Whether food, drugs or ideas, what you consume influences who you become. Learn directly from the best scientists & thinkers about alive today about how your body & mind react to what they’re fed.

The weekly M&M podcast features conversations with the most interesting scientists, thinkers, and technology entrepreneurs alive today.

Learning philosophy

At M&M, we are interested in trying to figure out how things work, not affirming our existing beliefs. We prefer consulting primary rather than secondary sources and independent rather than institutional voices. If we encounter uncomfortable truths or the evidence suggests unfashionable ideas may be valid, so be it.

As the host, my aim is to help you better understand how the body & mind work by curating & synthesizing information in a way that yields science-based insights that you can choose to use or disregard in your own life. Taking ownership of your health starts with taking ownership of your information diet.

I am motivated to connect the dots and distill general principles from what I learn, preferring to ask questions and play devil’s advocate to debating or pushing my own viewpoint.

My beliefs:

• Taking ownership of your health starts with taking ownership of your information diet.
• All knowledge is provisional and we must work hard to prevent ourselves from becoming attached to our favorite ideas & preferred conclusions.
• Wisdom comes from an iterative, trial-and-error process of learning and unlearning. Letting go of pre-conceived notions can be painful, but pain is information.

Sometimes modern discoveries teach us we must unlearn received wisdom. Other times, modern information overload & historical chauvinism cause us to forget ancient wisdom which stills applies. The framework for learning that I embody is inspired by three Ancient Greek maxims inscribed in the Temple of Apollo at Delphi:

• “Γνῶθι σεαυτόν” (Know thyself)
• “Μηδὲν ἄγαν” (Nothing in excess)
• “Ἐγγύα πάρα δ Ἄτα” (Certainty b

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Nick talks to psychiatrist & neuroscientist Devanand Manoli, MD, PhD, whose lab at UCSF studies the neural basis of social behavior & attachment in prairie voles. As a psychiatrist, he also treats patients with childhood psychosis. They discuss: the neural basis of pair bonding, monogamy, and parental & sexual behavior; oxytocin, vasopressin, testosterone & estrogen; evolution of behavior; menopause & multigenerational parental care; childhood psychosis; and more.

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Nick talks to Dr. Paul Cisek, a neuroscientist at the University of Montreal who studies sensorimotor control & decision making in primates. They discuss: the evolution of the brain from the earliest nervous systems to humans; metabolism & state control; the evolution of behavior; sensation, perception, cognition, decision making & consciousness; language & representation; why neuroscience needs evolutionary thinking; and more.

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Nick talks to Dr. Stephen Simpson & Dr. David Raubenheimer, both professors at the University of Sydney who have been research collaborators for many years. Their research focuses on understanding animal feeding behavior, especially how & why different animals use their sensory systems in order to consume foods so that their diets contain the right balance of nutrients. Understanding animals in the evolutionary & ecological contexts they evolved to survive in enables us to build a holistic picture of the general principles underlying feeding behavior. Topics discussed include: Macronutrients (protein, fats & carbohydrates) and micronutrients (sodium, calcium); the 'protein leverage hypothesis' & how this explains the modern obesity epidemic; how different diets can promote fat weight, longevity, or reproductive success; the optimal macronutrient composition for weight loss; the comparative biology of feeding behavior across animals like humans, gorillas, spiders, wolves, etc.

The discussion is based on their book, "Eat Like the Animals: What Nature Teaches Us About the Science of Healthy Eating."

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Nick talks to Dr. Christoffer Clemmensen, who runs the Metabolism & Molecular Pharmacology group at the University of Copenhagen in Denmark. His lab studies the biological basis of obesity & other metabolic disorders. They discuss: the causes of obesity; environmental and biological factors influencing predisposition to obesity; novel anti-obesity drugs; gut hormones & peptides regulating food intake; whether psychedelics like psilocybin may be useful for treating obesity and other metabolic disorders.

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Nick talks to academic dermatologist Dr. Richard Weller about: skin health; benefits & risks of sunlight & UV radiation exposure; nitric oxide, blood pressure & cardiovascular health; vitamin D; sun screen & tanning; the evolution of skin color & skin physiology; and more.

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Nick talks to biologist Dr. Christoph Thaiss, a professor at the University of Pennsylvania. His lab studies how the body detects & responds to environmental stimuli, with a focus on interactions between the gut microbiome, immune & nervous systems. They discuss: sensory systems of the body & basic principles of how they work; gut microbiome & the consequences of depleting it with antibiotics; endocannabinoids & exercise; how microbiome composition influences the brain & motivation to engage in exercise; prebiotics & probiotics; circadian rhythms & eating patterns.

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Nick talks to biochemist & biophysicist Dr Ryan Gumpper, a postdoc in Dr. Bryan Roth's lab at the University of North Carolina. They discuss the biochemistry, molecular biology & biophysics of serotonin receptors, including the molecular details for what happens when serotonin and tryptamines psychedelics (e.g. LSD) bind to 5HT2A receptors in the brain. They also discuss how understand these details relates to the quest to discover novel psychedelic-derived compounds with therapeutic benefits, as well as the inspiration Ryan received from reading Alexander Shulgin's famous book, PIHKAL.

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Nick talks to anesthesiologist & neuroscientist Dr. Alex Proekt, who runs a lab at the University of Pennsylvania, about altered states of consciousness. They discuss: NREM & REM sleep, anesthesia & anesthetic drugs like propofol; coma & vegetative states; sleeping pills like Ambien; the relationship between consciousness & the underlying brain dynamics; how ketamine differs from other anesthetics & what it does to brain activity; AI & ChatGPT.

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Nick talks to Jay Bhattacharya, MD, PhD, who is a professor of medicine & economics at Stanford University. They discuss various aspects of the COVID pandemic, such as: how infectious, transmissible, and deadly SARS-CoV-2 is; mRNA vaccines, how well they stop transmission vs. severed COVID, and whether they can induce negative side effects such as myocarditis; how well masks actually work; Jay's inclusion in the "TwitterFiles" and the suppression of speech on social media; what he thinks of Elon Musk after meeting him; his thoughts on the future of public health governance in the US.

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Nick talks to Dr. Sergiu Pasca, a developmental neuroscientist and professor at Stanford University. They discuss topics related to human brain development, the origins of neuropsychiatric disease like autism & schizophrenia, new technologies for studying brain development, stem cells, and recent experiments from Dr. Pasca'a lab utilizing brain "organoids," "assembloids," and human-animal transplantations.

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Nick talks to computational neuroscientist Dr. Zach Mainen, a neuroscientist and director of the Champalimaud Neuroscience Programme at the Centre of the Unknown in Lisbon, Portugal. His lab studies the neuroscience of decision making, neuromodulation & behavior using both experimental and computational approaches.

They discuss: what kinds of things animal brains are actually computing, and to what extent we can think about brains like computers; the difference between neurotransmitters and neuromodulators in the brain, including some discussion of what specific neuromodulators like dopamine and serotonin do in the brain; and we also discussed some of the research his lab is starting to do on serotonergic psychedelics, including how he thinks about whether the subjective effects of psychedelics are likely to be important for the therapeutic and neuroplastic effects.

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Nick talks to mathematical biologist Dr. Alex Washburne about the origins of the SARS-CoV-2 virus.

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Nick talks to experimental psychologist Dr. Harriet de Wit, a professor at the University of Chicago whose lab studies the behavioral effects of psychoactive drugs on humans. They discuss: the effects of MDMA on emotional perception and touch sensation; the effects of microdosing LSD; THC's impact on memory.

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Nick talks to biological anthropologist & neuroscientist Dr. Terrence Deacon, who is a professor of biological anthropologist at UC-Berkeley and a leading thinker on the evolution of language, consciousness and human cognition. They discuss: how end-directed systems, such as life, can emerge from non-life; how complexity evolves once life originates; the origins of sentience and a sense of self; the evolution of the nervous system and consciousness; information, value, and "aboutness" in the universe; and more.

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Nick talks to neuroscientist Dr. Kent Berridge, a professor of psychology & neuroscience at the University of Michigan. They discuss: the neurobiology of the brain processes rewards and generates pleasure & motivation; the difference between "liking" and "wanting"; hunger and whether food addiction is similar to drug addiction; emotion and consciousness; and more.

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Nick talks to Dr. Amir Englund, a psychopharmacologist at the Institute of Psychiatry, Psychology & Neuroscience at King's College, London. Dr. Englund's research focuses on the effects of cannabis, medical marijuana and specific cannabinoids (e.g. THC, CBD, THCV) on human cognitive function. They discuss topics including: what is the addiction liability of marijuana? What are the acute & chronic cognitive effects of THC, including how it impacts memory & executive function; how the effects of THC can be modulated by cannabinoids like CBD & THCV; the relationship between marijuana & THC and psychosis (e.g. schizophrenia); and more.

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Nick talks to molecular physiologist Dr. Dudley Lamming, a professor of medicine at the University of Wisconsin-Madison whose lab studies how the body responds to the nutrient and calorie content of food. We discuss: how the protein and amino acid composition of food impacts metabolic health & aging; branched chain amino acids & disease; sex differences between males & females in how diet affects health; fasting, calorie restriction & fasting; and more.

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Nick talks to genetics researcher & writer Razib Khan. Razib did graduate work in genetics at the University of California-Davis and recently founded a genomics data startup. He also runs a Substack, "Unsupervised Learning," where he writes a lot of fascinating articles on the subjects of human evolutionary & population genetics, personal genomics, and more. Nick and Razib discussed: how the story of human evolution has changed over the past two decades; genomics technology & ancient DNA; Neanderthals, Denisovans & ancient humans; personal genomics (e.g. 23AndMe, Ancestry.com); Razib's experience as a writer on Substack.

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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick talks to Christian Lüscher, MD, PhD, a neuroscientist at the University of Geneva whose lab studies the cellular mechanisms that underlie drug reinforcement, dependence and addiction. Dr. Lüscher talks about the nature of addictive drugs in the brain, how ketamine works, and the latest research from his lab look at how ketamine's unique effects within the brain's reward circuitry enable it to be psychoactive & reinforcing, but have a very low addiction liability (in rodents). He also discusses what this research may mean for the use of ketamine as a therapeutic treatment for depression in humans.

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Nick talks to neuroscientist Dr. David Anderson, a professor at Caltech whose lab studies the neurobiological basis of animal behavior and emotion. They discuss: technologies for understanding cause-and-effect in the brain; neurobiological basis of animal behavior, including aggression/fighting, mating, feeding, and social behavior; how hormones such as estrogen regulate behavior; emotions, feelings, and consciousness; and David's new book, "The Nature of the Beast."

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Nick talks to psychiatrist Dr. Joanna Moncrieff about depression. What causes it? How do SSRIs work? How well do antidepressants work? What are the risks & benefits of long-term antidepressant use? What is the evidence that depression is caused by a chemical imbalance (too little serotonin) in the brain? How is social media & technology influencing mental health?

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Nick talks to journalist & documentary filmmaker Leighton Woodhouse. They discuss: homelessness & drug addiction; religion & ideology; sociology & social psychology; the social function of laws and norms; economic vs. cultural capital & the "overproduction of elites"; institutional science; civilizational decline & the future of American society.

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Nick talks to anthropologist Dr. Michael Winkelman, who was a professor at Arizona State University for many years, where he studied topics related to shamanism as practiced by early hunter gatherer societies, and other topics related to human cultural evolution. He is now retired and conducts independent research from Brazil, where he now lives. They discuss: what shamanism is & the core features of shamanic ritual practices across historical hunter gatherer cultures; how the various ritual practices associated with shamanism were used by forager societies (e.g. symbolism, group dance and drumming) & the use of psychedelics; evolution of shamanism & religion from prehistoric times to the present; role religion and spiritual practices have played in human evolution; how human culture is akin to virtual reality & how human ritual practices help sculpt the narratives that form within human cultures that regulate human behavior; future of religion & spirituality in the modern age & whether the use of psychedelics as entheogenic substances might have a role to play in that.

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Nick talks to pharmaceutical microbiologist Dr. Dirk Hoffmeister, who is professor at the Hans Knöll Institute in Germany. Professor Hoffmeister has a background in botany and mycology, the study of fungi. His lab studies various aspects of fungal biochemistry & molecular biology, including the biochemistry and molecular genetics of psilocybin production in magic mushrooms.

We spoke about various topics in mycology, mostly related to Psilocybe mushrooms. This included: how psilocybin is synthesized from the amino acid tryptophan; the ecological reasons for why some mushrooms produce psilocybin; why magic mushrooms turn a vibrant blue color when they are physically damaged; the production of monoamine oxidase inhibitors (MAOIs) by certain species; the ecology of Psilocybe mushrooms; other areas of mycology that his lab studies.

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Nick talks to climatologist Dr. Judith Curry, the former chair of the School of Earth and Atmospheric Sciences at the Georgia Institute of Technology. Her research interests have included hurricanes, atmospheric modeling, air-sea interactions, and a variety of other areas in climate science. She runs Climate, Etc., an online blog focused on climate science. She is also writing a new book called, “Climate Uncertainty & Risk,” which she described towards the end of the podcast.They discuss: how Earth’s climate has changed over time and how climate scientists measure this; what computer models are used for in climate science and what their strengths & weaknesses are; tropical storms and severe weather events; CO2, methane, and other greenhouse gasses; different forms of energy, such as oil, natural gas, solar, wind, and nuclear; how she thinks about the tradeoffs between different energy sources in terms of their abundance, environmental impact, costs, and other factors; the politicization of climate science and why certain branches of science are especially prone to it.

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Nick talks to Dr. David Cohen, a professor at the UCLA Luskin School of Public Affairs. His research looks at psychoactive drugs (prescribed, licit, and illicit) and their desirable and undesirable effects as socio-cultural phenomena “constructed” through language, policy, attitudes, and social interactions. They discuss: prescription psychiatric drugs, including SSRIs, benzodiazepines and stimulants (e.g. Adderall); the history of how some of the most widely prescribed psychiatric drugs came to be so popular; how pharmaceutical companies go about marketing these drugs and the conditions they aim to treat to both physicians and the public; the quality of the evidence supporting their use; what we are learning about the potential for dependency, long-term health effects, and actual level of benefit that comes from chronic psychiatric drug use; why many psychiatric drugs are increasingly prescribed in combination; and more.

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Nick talks to Dr. Shruti Naik, assistant professor of pathology & medicine at the NYU Langone. Her lab studies the interactions between immune cells, epithelial cells, and microbes in barrier tissues that interface with the environment (e.g. skin, lungs & gut). They discuss: inflammatory memory; how cells store memories of inflammation epigenetically; how skin cell regenerate and repair tissue damage; stem cell biology; cancer, and more.

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Nick talks to neuroscientist Dr. Margaret McCarthy, whose lab at the University of Maryland studies the origins and mechanisms of sex differences in the brain, the endocannabinoid system, and neural basis of animal behavior. They discuss: the nature of sex differences observed in the mammalian brain, including differences in the susceptibility to various diseases and disorders of the brain; differences in juvenile play behavior in males vs. females, and how these can be altered by sex hormones and cannabinoids; sex differences in brain development that lead to sex differences in behavior; how the endocannabinoid system influences brain development and behavior; how cannabis use during pregnancy may influence brain development.

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Nick talks to science writer Matt Ridley, who most recently published the book, "Viral: The Search for the Origin of COVID-19" together with molecular biologist Dr. Alina Chan. They discussed what is known and still unknown about the origins of the SARS-CoV-2 virus, the latest developments in that mystery which have come to light in the past few months; the relationship between institutional science and politics; whether we are ever likely to know definitively the origins of this virus, and more.

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Nick talks to medicinal chemist Sam Banister, who is co-founder and Chief Science Officer at Psylo, a biotech startup focused on developing next-generation psychedelic medicines. They discuss: the past, present, and future of psychedelic science; Sam's journey from academia to biotech startup co-founder; Alexander Shulgin; psychedelics like psilocybin, DMT, and others; and psychedelics & society.

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Nick talks to neuroscientist & geneticist Dr. Kevin Mitchell about: 'Nature vs. Nurture,' the genetics of brain development, autism & schizophrenia, human brain and psychological variation, synesthesia, agency & free will, and more.

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Nick talks to neurologist & neuroscientist Michael Fox, MD, PhD about his recent work mapping out an "addiction remission network" in the brain. They discuss addiction, brain networks involved in addiction, neurotechnologies like Deep Brain Stimulation and Transcranial Magnetic Stimulation, Parkinson's Disease, and more.

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Nick talks to physiologist and neuroscientist Dr. Dominic D'Agostino about human metabolism & nutrition; fats, carbohydrates, sugar, and protein; ketogenic diet, ketosis, BHB supplementation; inflammation and polyunsaturated fats; personal health and metabolism monitoring; and general questions related to the quality of the nutritional information we receive from our institutions.

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[https://www.elysiumhealth.com/discount/MIND]

DoubleBlind Magazine, a leading source of news, information, and education about psychedelics. Use code MINDMATTER for 20% site-wide.
[https://www.doubleblindmag.com/mindmatter]

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Nick talks to anthropologist Dr. Dimitris Xygalatas, who is an associate professor at the University of Connecticut. His research interests center around human ritual behavior and the interaction between cognition and culture. They discuss his new Book, "Ritual: How Seemingly Senseless Acts Make Life Worth Living." Topics covered: Rituals vs. habits; the psychological purpose of ritual; ritualism as an antidote to anxiety; religion and spiritual practices; culture & the birth of civilization; the physiological and psychoactive effects of ritual; Ayahuasca and psychoactive drugs; rituals in sports, gambling, and other human activities; the evolution of language & symbolic cognition; religion, community & Burning Man.

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DoubleBlind Magazine, a leading source of news, information, and education about psychedelics. Use code MINDMATTER for 20% site-wide.
[https://www.doubleblindmag.com/mindmatter]

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Nick talks to cognitive psychopharmacologist Dr. Manoj Doss about the effects of psychoactive drugs on memory, including sedatives, stimulants, psychedelics, cannabinoids, and MDMA. They also talk about recent research on the effects of psilocybin on the human brain.

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[https://www.elysiumhealth.com/discount/MIND]

DoubleBlind Magazine, a leading source of news, information, and education about psychedelics. Use code MINDMATTER for 20% site-wide.
[https://www.doubleblindmag.com/mindmatter]

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Nick talks to neuroscientist Dr. Joseph LeDoux, who runs a research lab at New York University. His research focuses on the neurobiology of emotion, memory and behavior and he has written several popular science books including, "The Deep History of Ourselves." They discuss: brain evolution; what is behavior? what are emotion and cognition, and how are they intertwined; consciousness, language, and memory.

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[https://www.elysiumhealth.com/discount/MIND]

DoubleBlind Magazine, a leading source of news, information, and education about psychedelics. Use code MINDMATTER for 20% site-wide.
[https://www.doubleblindmag.com/mindmatter]

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Dr. Maayan Levy is an assistant professor of microbiology at the University of Pennsylvania, where her lab studies the communication between the microbiome and its host, with a focus on the gut microbiome and its relationship to diet, immune system function, and disease. We discuss: her recent study linking the ketogenic diet to lower risk of colon cancer; what the ketogenic diet is and what the metabolic state of ‘ketosis’ does in the body; molecules called ketone bodies, such as BHB, and the extent to which BHB supplementation can recapitulate some of the physiological effects of the ketogenic diet; how the microbiome influences the function and development of the immune system; and the hygiene hypothesis, the idea that modern human cultures may be too clean, or rely too heavily on antibiotics and other technology, and interfere with our microbiome in ways that may be detrimental to metabolic and immunological health.

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DoubleBlind Magazine, a leading source of news, information, and education about psychedelics. Use code MINDMATTER for 20% site-wide.
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Nick talks to chemist & patent attorney Dr. Andrew Chadeayne, who is the CEO of the psychedelic startup CaaMTech. They discussed: the chemistry of magic mushrooms, including compounds beyond psilocybin, found in many species of psilocybin-containing mushrooms; the so-called entourage effect, the idea that multiple compounds found in plants and fungi might work together in a synergistic fashion to produce specific psychoactive or therapeutic effects; Cannabis and magic mushrooms; DMT, 5-MeO-DMT, and novel DMT analogues; how we went from academia, to patent law, to founding CaaMTech; the prospect of developing novel psychedelic drugs, non-hallucinogenic psychedelic drug analogues, and some of the details on how these various drugs differ in terms of their chemical structure.

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DoubleBlind Magazine, a leading source of news, information, and education about psychedelics. Use code MINDMATTER for 20% site-wide.
[https://www.doubleblindmag.com/mindmatter]

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Nick talks to Dr. Martin Picard, a biologist at Columbia University whose lab studies mitochondrial psychobiology, linking together molecular processes within mitochondria with human experience. They discussed; what mitochondria are and where they came from: their role in energy & metabolism; the mitochondrial genome; the importance of mitochondria in stress & aging; how exercise, diet, and genetics influence mitochondria biology; hair graying and whether it's reversible; the mind-mitochondria connection.

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[https://www.elysiumhealth.com/discount/MIND]

DoubleBlind Magazine, a leading source of news, information, and education about psychedelics. Use code MINDMATTER for 20% site-wide.
[https://www.doubleblindmag.com/mindmatter]

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Nick talks to biologist Dr. Leonard Guarente about the biology of aging, life extension, health supplements, and related topics. Dr. Guarente is a Professor of Biology at MIT, where his lab has studied the molecular and cellular mechanisms of aging for many years. He is also the co-founder and Chief Scientist of Elysium Health, which uses the science of aging to develop health supplements to combat age-related decline and technologies to help consumers understand their rate of aging.

Nick and Dr. Guarente discussed many topics related to aging, including: how and why aging occurs; whether humans can achieve immortality; NAD and the core metabolic processes of cells; resveratrol, pterostilbene, and other anti-aging molecules; epigenetics and technology that can be used to calculate biological age vs. chronological age.

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Nick talks to cell & developmental biologist Dr. Blanche Capel. They discussed the nature of sexual reproduction and sexual dimorphism, including when these these things evolved, the evolutionary reasons for sexual reproduction, and the amazing diversity of mechanisms that determine the development of sexual traits across the animal kingdom; the contribution of genetic vs. environmental factors in sex determination, and how these vary across species; sex chromosomes, such as the X and Y chromosomes of humans and other mammals; sex hormones, such as testosterone and estrogen; as well as how gametes and gonads develop - these are the sex cells, such as sperm or egg, and the reproductive organs that produce them and the major sex hormones that shape sexual development; what we know, and don’t know, about the biology of puberty and sexual development after birth, as well as whether environmental factors, such as components of the diet an environmental contaminants, could be influencing sexual development.

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Nick talks to neuroscientist & clinical researcher Dr. Rachel Yehuda, who is a professor of psychiatry & neuroscience at the Icahn School of Medicine at Mount Sinai, in New York. They discuss the biology and neuroscience of stress, PTSD (post-traumatic stress disorder), why people can be sensitive or resilient to stress, epigenetics, intergenerational trauma, and how MDMA and psychedelics are being explored for their ability to treat stress-related mental health conditions.

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Nick speaks to writer Robert Greene, who is the author of several books exploring different, and sometimes dark, aspects of human psychology. The discussion focuses on the subject of his first book, "The 48 Laws of Power."

They discuss what power is and how it's used. Different psychological traits that people who successfully acquire power tend to have. Strategies that have been useful throughout history for acquiring more power, as well as those that lead to a loss of power. Robert talks the political scientist Niccolo Machiavelli, and how he is often misunderstood. He also gave his perspective on some influential people with power today, including Vladimir Putin, Angela Merkel, and Elon Musk.

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Nick talks to cognitive scientist Dr. Donald Hoffman, who is professor emeritus of cognitive sciences at UC-Irvine and the author of many scientific papers and books, including "The Case Against Reality: Why Evolution Hid the Truth from Our Eyes.”

They discussed a variety of topics related to consciousness, the nature of perception, and evolution, including: how perception works; whether our conscious perceptions are accurate representations of underlying reality; the interface theory of perception, which likens our conscious perceptions to the digital icons displayed on your computer screen; language; psychedelic experiences; and the nature of reality itself, such as whether space and time are fundamental aspects of the universe, or artifacts of perception.

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Nick talks to biochemist Joe Baur, PhD, whose lab at the University of Pennsylvania studies the molecular mechanisms of aging and metabolism. These discuss: aging as a passive vs. regulated process; mechanisms of aging (DNA mutations, oxidative stress, etc.); NAD and its role in normal physiology; the biology of sirtuins; rapamycin as an immunosuppressant & modulator of aging; the effects of diet & caloric restriction on aging; the potential slowing and reversing aging, and more.

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Nick talks to Dr. John Cryan, a Professor of Anatomy & Neuroscience at University College-Cork in Ireland whose lab studies the microbiota-gut-brain axis in health & disease.

They touch on a range of topics related to how our gut microbiome affects the brain and body, including: how the microbiome affects aging and immunity; how it affects social behavior, including potential links to autism; how antibiotics and the general hyper-cleanliness of the modern world impacts the microbiome; how it affects neuropsychiatric conditions like depression; how diet influences brain inflammation; towards the end John also shared an interesting example of a food he consumes for gut health.

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Nick talks to Dr. Gul Dolen, a professor of neuroscience at Johns Hopkins University. Her lab studies the circuit and synaptic mechanisms of social cognition in health and disease.

Nick and Dr. Dolen discussed her research on critical periods for social reward learning in rodents, the role of oxytocin in social behavior and learning, and how MDMA ("ecstasy") promotes prosocial behavior in animals as diverse as humans, rodents, and octopuses. They also talked about how drugs like MDMA and psychedelics influence "metaplasticity," enabling environmental factors to trigger plasticity (physical changes in the brain) in a context-specific manner. Dr. Dolen also described how her research relates to developing treatments for autism, as well as her thoughts on whether the subjective effects of psychedelics and other drugs are necessary for some of their therapeutic effects.

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Martin Kulldorff, PhD is an epidemiologist & biostatistician who has been studying infectious diseases for over two decades. He was a professor at Harvard Medical School for many years, a member of the FDA’s Drug Safety & Risk Management Advisory Committee, and a former consultant for the Centers for Disease Control. In 2020, Dr. Kulldorff co-authored the Great Barrington Declaration, a document criticizing the use of society-wide lockdowns for COVID-19 and advocating for a strategy of focused protection for high-risk people.

Nick and Dr. Kulldorff discussed a variety of topics related to the COVID pandemic, including the nature of how the SARS-CoV-2 virus spreads compared to other pathogens, how our public health strategy was implemented & his thoughts on how we could have handled the pandemic better, vaccine-induced immunity vs. natural immunity, vaccine efficacy, how and why various countries differed in their approach to COVID, and the health of our scientific & public health institutions in the US.

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Nick talks to computer scientist and philosopher Bernardo Kastrup about various topics related to consciousness and the nature of reality. They discuss: psychological dissociation; the scientific study of 'neural correlates of consciousness'; the nature of perception and the influence of language on the mind; why the 'Hard Problem' of consciousness is so difficult; Bernardo's philosophy of analytic idealism; Jungian psychology & psychological archetypes; psychedelic experiences with psilocybin, 5-MeO-DMT, and how these could model the phenomenology of organic death.

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Nick Jikomes talks to cancer biologist Dr. Marsha Rosner, who is a Professor of Cancer Research at the University of Chicago. Her lab focuses largely on understanding the biochemical signaling mechanisms that lead to the generation of tumor cells, as well as how and why cancer cells metastasize, which is when they travel from one part of the body to another.

Nick and Dr. Rosner and discuss mainly a recent study she led about the antiviral effects of cannabidiol (CBD) against SARS-CoV-2, including: why a cancer lab was working with CBD to begin with; what the results of her study actually show in terms of CBD’s antiviral effects; whether other cannabinoids showed this effect. She also commented on some misconceptions that have been circulating regarding this work, and described some of the clinical trials her team is running to measure CBD’s potential as an anti-COVID drug.

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Kevin McKernan is a renowned leader in DNA sequencing technology. He led a research team part of the original Human Genome Project and is the founder and Chief Science Officer of Medicinal Genomics, a life sciences company that distributes genetics-based platforms for quality and safety testing of legal cannabis.

Nick and Kevin discussed the Cannabis genome, the genome of Psilocybe cubensis (magic mushrooms); Polymerase Chain Reaction (PCR) technology, how it works, and how it's used for COVID-19 testing; cannabinoids such as cannabidiol (CBD) and recent research indicating their potential anti-SARS-CoV-2 effects; blockchain technology for genomics data; and mRNA vaccines and SARS-CoV-2.

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Nick talks to Alexandra Elbakyan, the founder of Sci-hub, a shadow library website that provides free access to millions of research papers and books, without regard to copyright, by bypassing publishers' paywalls in various ways. Sci-hub is used by millions of people around the world each month, granting them free and easy access to scientific research findings.

Nick spoke to Alexandra about how Sci-hub works, why she built it, and some of the legal challenges she has faced from large scientific publishing corporations. This conversation was conducted with a professional Russian-English translator, whose voice you will hear in the recording in place of Alexandra's.

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Nick talks to Dr. Suzanne Devkota, a microbiologist whose lab studies the gut microbiome in health and disease.

They discuss a variety of topics related to the gut microbiome: how it is influenced by diet; how antibiotics and probiotics affect it; different disease states and metabolic disorders, such as IBS and obesity; how gut microbes can affect the brain and behavior; the microbiome beyond the gut, including the skin; and more.

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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick talks to Dr. Amy Reichelt, a neuroscientist and expert on the effects of diet and nutrition on the brain. They discussed how the brain is wired to help us learn about food, how what we eat influences the function of circuits within the brain, how certain diets can actually cause damage to the brain and negatively impact learning, obesity, and other topics related to nutrition and feeding behavior in humans and animals. They also discuss the potential role that psychoactive drugs like psychedelics may have to play in treating food addiction.

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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick talks to Dr. Paul Barrett, a paleontologist at the Natural History Museum in London, UK. Paul has spent nearly 30 years as a paleontologist studying the evolution and biology of dinosaurs and other extinct reptiles. He has authored over 200 scientific papers, and his speciality is in non-avian dinosaurs.

Nick talked to Paul about all things dinosaurs, including what a dinosaur actually is; how and when dinosaurs first evolved, changed over time, and eventually went extinct; what we know about dinosaur behavior, morphology, and physiology; which dinosaurs had feathers and what colors they had; Tyrannosaurus rex and Velociraptor; the evolution of mammals; the movie Jurassic Park; and why understanding the life's past is important for understanding life in the present.

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Nick talks to Dr. Reggie Gaudino, a molecular geneticist and expert in the phytochemistry, biochemistry, genomics, and breeding of commercial Cannabis. He is the former Chief Science Officer of Steep Hill, one of the first cannabis testing labs in the US, and is currently VP of Research & Development at Frontrange Biosciences.

Nick & Reggie discuss various topics related to the science of commercial Cannabis, including: it's botanical characteristics and history, the ecological reasons for why it produces psychoactive and other compounds, some of the major cannabinoids and terpenes found in Cannabis, and whether or not popular labelling systems in the legal cannabis industry (e.g. "Indica" vs. "Sativa") will tell you anything useful about the effects a product is likely to have.

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Nick Jikomes talks to Dr. David Roberson, a neuroscientist and co-founder of three ongoing biotech companies: Nocion Therapeutics, Blue Therapeutics, and Blackbox Bio. David is an expert in the neuroscience of pain and the conversation focuses mainly on pain: how does our brain sense and perceive pain? Why does pain sometimes become chronic, and last for a long-time? How do various classes of pain drugs work to relieve pain?

They discuss NSAIDs and opioids, including oxycodone, heroin, and fentanyl, as well as some interesting novel pain drugs currently in development.

A portion of the podcast has a visual component, where David shows some of the technology he has helped develop that allows for automated, high-throughput measurements of animal behavior to detect and measure pain. Towards the end, they also discuss how this tech could be used for the characterization of novel psychoactive drugs and psychedelics.

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Nick talks to Alexandros Marinos, PhD, founder & CEO of the edge computing technology startup, Balena. They discuss the internal organization of complex human systems.

Alex talked about how he thinks about the organizational structure of his own company and how organizational structures impact group dynamics, growth, conflicts of interest, and innovation. One interesting area Alex provided commentary and analysis on towards the end is how to make sense of the behavior of large institutional organizations, such as the Centers for Disease Control (CDC).

If you’re interested in complex systems like human organizations, how the internal structures of different organizations influence what they do and how they behave, and why human organizations can sometimes behave in deranged ways, this episode will be of interest to you.

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"The Methods & Motivations of Balena's Organizational Structure"
[https://ourovoros.substack.com/p/the-methods-and-motivations-of-balenas]

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Nick Jikomes talks to materials scientist Dr. Chris Weikart, who is currently chief scientist at SiO2, an advanced materials science company that combines chemistry and engineering to create containers and surfaces for use by biotechnology, genomics, diagnostics, and consumer products companies.

They discuss how SiO2 created a new kind of vaccine vial, which combines both glass and plastic that are superior for storing and transporting biologics, such as vaccines. SiO2 is currently producing an enormous number of these vials for Moderna’s mRNA vaccines for COVID-19. Chris described how the vials are made, and what they’re made of, as well as what materials science is and how important it is to society. This conversation also gives you a sense for different parts of the COVID vaccine supply chain and how they fit together.

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Nick Jikomes talks to Dr. Jonathan Schaefer about the link between adolescent cannabis (marijuana) use and psychosis.

Jonathan has a PhD in clinical psychology and he is currently a research psychologist at the University of Minnesota Institute of Child Development. His research focuses largely on the relationship between people’s environments that influence their mental health. He has conducted a number of longitudinal studies using cohorts of identical and fraternal twins, which allow him to tease apart the role of genetic vs. environmental factors in different psychiatric outcomes.

The conversation focuses mainly on recent twin studies Dr. Schaefer has done looking at the relationship between adolescent cannabis (i.e. marijuana) use, and psychosis. They talk about what psychosis is and what factors are linked to it, historical work on the relationship between cannabis use and psychosis, and the results of Jonathan's recent twin studies & what they mean.

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Nick Jikomes talks to Sam Wang, PhD professor of neuroscience at Princeton University. Dr. Wong’s lab investigates how brains learn from sensory experience, in adulthood and development, with relevance for autism. A lot of their work focuses on a part of the brain called the cerebellum.

They talk about the cerebellum and what we’re learning about its functions, as well as how it’s tied to autism, and what the causes and nature of autism actually are. This included both the genetic and environmental risk factors for autism, and how to think about treatment. Lastly, they talk about another side of his work, which is related to using data and science to help repair our democracy by combatting things like congressional gerrymandering.

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Nick Jikomes talks to Dr. Nathan Price, who has a PhD is in bioengineering and has been faculty at the University of Washington and the Institute of Systems Biology. He was also CEO of a health intelligence startup called Onegevity, which recently merged with Thorne HealthTech, which he is Chief Science Officer of.

Nathan and Nick discussed various topics in the realm of personalized medicine, digital phenotyping and systems biology, including things like metabolism & blood sugar monitoring, the microbiome & diet, aging & longevity, and more. They talked about the basic biology of these things, as well as different emerging technologies related to health monitoring.

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Nick Jikomes talks to medicinal chemist Dr. David Olson whose lab at the University of California-Davis studies a class of compounds called ‘psychoplastogens,’ which are small molecules capable of promoting neural plasticity. His lab is on the cutting edge when it comes to understanding the mechanisms by which psychedelics and other psychoactive drugs work in the brain. They touch on: latest research from his lab, new tools they're developing and using to understand these drugs, whether it’s likely that we'll be able to produce non-hallucinogenic drug variants of classic psychedelics, and microdosing.

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Nick Jikomes talks to genetic engineer Dr. Alina Chan about the origins of the SARS-CoV-2 virus responsible for the COVID-19 pandemic. They discuss Alina's new book, "Viral: The Search For the Origin of COVID-19," which she co-wrote with Matt Ridley. The book thoroughly documents the events & people relevant to COVID's origins. They discuss everything from the original SARS-1 epidemic in China, wildlife spillover vs. accidental lab leak hypotheses; pangolins, bats, and other animals; SARS-CoV-2 genome; institutions and people like Francis Collins, the NIH, WHO, and EcoHealth Alliance.

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Nick talks with Dr. Anil Seth, a neuroscientist and professor of cognitive & computational neuroscience at the University of Sussex. The conversation is all about the neuroscience of consciousness, which is the subject of his Dr. Seth's book, “Being You: A New Science of Consciousness.“

They touch on everything from what consciousness actually is, whether or not neuroscientists can measure different levels of consciousness in the brain, what characterizes psychedelic experiences and non-ordinary states of consciousness in terms of the brain, and the nature of perception. In particular, they discuss ideas related to the notion that our conscious perceptions are a kind of inference, or guess, our brain’s are making about the world, as well as the idea that all of our conscious perceptions are "controlled hallucinations."

They also discuss: exteroception (perceiving things outside the body, like objects); interoception (perceiving things within the body); and emotion. Lastly, Nick gets Anil’s take on whether consciousness is an evolutionary adaptation and psychedelics.

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Nick talks to neuroscientist and writer Dr. Erik Hoel. Erik is a professor of biology at Tufts University. He received his PhD in neuroscience from the University of Wisconsin, where he studied under the sleep and consciousness researcher, Giulio Tononi. He did postdoctoral work at Columbia University, where he used information theory and other analytical tools to explore the biological basis of consciousness. He has come up with the so-called Overfitted Brain Hypothesis of dreaming, which explains the potential adaptive function of dreams by drawing analogies to techniques used to train Deep Neural Networks in the world of machine learning.

Erik and Nick discuss the biology and phenomenology of dreams and sleep generally, including some of the various theories for why we sleep. They also discuss Deep Learning (on a very basic level) and Erik described the Overfitted Brain Hypothesis of dreaming. They also discuss fiction and the arts, including Erik’s new novel and the potential evolutionary reasons for why humans create and consume fiction, as well as some technology-driven developments that are reshaping how we create and consume written work online.

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​​​
Learn more about our podcast sponsor, Dosist
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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick Jikomes talks to Dr. Steven Laviolette, a neuroscientist at the University of Western Ontario. They discuss how different types of drugs impact emotion, cognition, brain development and the development of psychiatric conditions (e.g. addition, schizophrenia); drug interactions (THC + CBD, THC + L-Theanine, CBD + Omega-3 Fatty Acids), how drugs can affect brain development when consumed during adolescence, or by pregnant women; how cannabinoids interact with opioids in different ways.

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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick Jikomes talks to Saoirse O'Sullivan, PhD, a physiologist specializing in the physiological effects of cannabinoids. Dr. O'Sullivan ran a lab at the University of Nottingham for many years before becoming a consultant and Vice President of Translational Research at Artello Biosciences.

They discuss some of the physiological effects of cannabinoids in the body, including endogenous cannabinoids our own bodies produce, and plant cannabinoids associated with the Cannabis plant (e.g. THC, CBD, THCV, and CBG). They cover: inflammation, brain injury, the blood-brain barrier, gut health, the cardiovascular system. Near the end, Saoirse also described why she eventually transitioned from academia to the private sector, and what motivated her decision to do so.

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Christian Luscher, MD, PhD is a neuroscientist and neurologist who runs a research lab at the University of Geneva in Switzerland. Dr. Lusher's lab studies the mechanisms that underlie drug reinforcement and addiction in the brain and he is an expert in the neuroscience of drug addiction.

Christian talks to Nick Jikomes about: what is addiction is and what some key parts of the brain and neurotransmitter systems are involved in drug addiction; differences in the addictive potential of different types of drugs, ranging from stimulants (e.g. cocaine, nicotine, caffeine) to cannabinoids (e.g. THC), opioids, and psychedelics; the difference between addiction vs. dependency, habitual vs. goal-directed behavior; latest research on how dopamine & serotonin systems in the brain are both involved in drug-seeking behavior.

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Nick Jikomes talks to writer and science journalist Nicholas Wade about the origins of the SARS-CoV-2 virus and the COVID-19 pandemic. Nicholas describes how this story has evolved since the start of the pandemic, and contrasts the the two main hypotheses for the origins of COVID: wildlife spillover vs. lab leak. He describes how viruses in the past (e.g. SARS1) emerged, peculiarities of the SARS2 genome, Peter Daszak & EcoHealth Alliance, Wuhan Institute of Virology, and various conflicts of interest that people have had. He describes how we don't have proof whether a wildlife spillover or a lab leak explains the origins of COVID-19, what definitive evidence would look like, and whether we are likely to resolve this mystery.
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Nick Jikomes talks to paleoanthropologist Dr. Lee Berger about human evolution. Dr. Berger is a professor of anthropology in South Africa, explorer-in-residence for National Geographic, and author of, "Becoming Human." Lee's team has mapped and explored caves all over South Africa, discovering a treasure trove of ancient human fossils. This includes the discovery of Homo naledi, an ancient human ancestor that had a much smaller brain than humans, but may have nonetheless harbored advanced cognitive abilities. Lee described the discovery of Homo naledi, human brain evolution, and why we are in a gold age of paleoanthropology.

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Nick talks to physicist and neuroscientist Dr. Michael Crair. Michael runs a lab at Yale University studying mechanisms of brain development. He discussed research related to neural plasticity, learning & memory, sensory maps, and critical periods of plasticity. Dr. Crair also described recent findings from his lab show that parts of the developing brain can simulate future sensory experiences, before animals ever open their eyes and see the external world.

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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick talks to evolutionary biologists Bret Weinstein & Heather Heying about using evolutionary thinking to understand humanity's predicaments in the 21st century. They discuss a variety of topics related to their new book, "A Hunter Gatherers Guide to the 21st Century," including modern medicine, dieting & health, sleep & light, dating & mating systems, and questions related to consciousness and the state of civilization at large. The book is meant to provide an evolutionary toolkit for understanding the modern human condition by understanding our past.

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ABOUT Nick Jikomes
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick talks to Stanford psychiatrist and neuroscientist Dr. Karl Deisseroth. They discuss a range of topics about the brain, including autism, depression, bipolar disorder, dissociation, and more. They also talk about optogenetics, a technique Karl co-developed which uses light to control specific neurons in the brain, allowing neuroscientists to turn circuits in the brain on and off to reveal how the brain generates perception, emotion, and behavior. They also talk about Karl's new book, "Projections: A Story of Human Emotion."

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​​​
Learn more about our podcast sponsor, Dosist
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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick to talks to psychology student Rob Henderson about social status, social signaling, luxury beliefs, and related topics in social psychology and human behavior.

Connect with Rob Henderson on Twitter: @robkhenderson

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​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick talks to medicinal chemist Dr. David Nichols, who has spent decades studying the chemistry and pharmacology of psychedelics. Dr. Nichols shared his knowledge of psychedelic tryptamines, including LSD and DMT, as well as phenethylamines, such as mescaline and MDMA. He also discussed his relationship with the late Dr. Alexander "Sasha" Shulgin, and how his thoughts companies trying to make non-hallucinogenic drugs derived from psychedelics.

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Connect with Nick Jikomes on Twitter
[https://twitter.com/trikomes]
​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks with evolutionary biologist Dr. Sarah Otto about the evolutionary dynamics of SARS-CoV-2, the emergence of new variants, whether she thinks we will need shots every year (like with the flu), mRNA vaccines, and more.

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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick talks to neuroscientist Dr. Aaron Gruber about topics related to cognition and learning in the brain, including what we know about how the brain detects salience and assigns value, makes decisions, and constructs flexible models of the world, sometimes called ‘schemas.’ They also discuss how neuropsychiatric disorders like depression can influence the brain’s schemas, as well as how they can be impacted by psychoactive drugs, ranging from stimulants to psychedelics.

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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick talks to applied physicist and neuroscientist, Dr. Alex Kwan. His lab studies how neuropsychiatric drugs, such as psilocybin and ketamine, affect neural circuits in the brain’s of mice. They discuss how his lab actually conducts this research, what they have discovered so far, and look at some real data, images and movies of neurons in the brain, which you can see for yourself in the video version on YouTube.

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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to neuroscientist Dr. Lisa Monteggia about research on psychiatric disorders of the brain. Lisa described how psychiatric disorders like depression manifest in the brain, how traditional anti-depressant drugs like SSRIs work in the brain, and her research on how the drug ketamine can have rapid depressant effects in treatment-resistant patients.

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[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to chemist Dr. Lee Cronin about life: how it originated on Earth, how we might detect signs of alien life in the universe, whether it can be created in the lab, and related topics. Lee talked about his work on "assembly theory," which provides a framework for thinking about these questions and providing an unbiased way to detect signatures of life in the universe. They also discussed how some of these ideas might relate to evolution, selection, consciousness, and time.

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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Harvard-MIT geneticist George Church, PhD talks about advances in genome sequencing and editing technologies, interesting biotech startups using CRISPR genome editing to tackle human disease, and interesting areas in synthetic biology. Dr. Church also discussed how he has coped with both narcolepsy and dyslexia throughout his life, and became a successful scientist despite have these brain disorders.

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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to Dr. Berra Yazar-Klosinski, the Chief Science Officer for the Multidisciplinary Association for Psychedelic Studies (MAPS). Berra talked about the results of MAPS' recent Phase III clinical trials for treating severe PTSD, how these studies are conducted, and what we know about the underlying biology of Post-Traumatic Stress Disorder (PTSD) and the drug MDMA.

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Athletic Greens, comprehensive daily nutrition (Free 1-year supply Vitamin D w/ purchase)
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Organize your digital highlights & notes w/ Readwise (2 months free w/ sub)
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[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to neuroscientist & psychologist, Dr. Chris Timmermann, ascientist at the Centre for Psychedelic Research at Imperial College London. Chris led the first neuroimaging studies on the effects of the potent tryptamine psychedelic DMT on the brain. They discussed DMT and related psychedelics, including how DMT is normally consumed in both recreational and laboratory contexts, how people describe its effects, how it compares to psychedelics like psilocybin and LSD, and whether it is an endogenous compound present in our own bodies. Chris also described his research on how DMT affects patterns of brain activity, and what he hopes to learn from ongoing research, which includes extending the duration of DMT experiences from a few minutes up to 30 minutes per session.

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[https://linktr.ee/mindandmatter_books]

Athletic Greens, comprehensive daily nutrition (Free 1-year supply Vitamin D w/ purchase)
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[https://linktr.ee/trikomes]

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[https://dosist.com/]

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Nick talks to gastroenterologist and neuroscientist, Dr. Emeran Mayer. Emeran is a distinguished professor at UCLA and an expert in gut health and the microbiome. His last book was titled, “The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts Our Mood, Our Choices, and Our Health.” His latest book builds on this, and is titled, “The Gut-Immune Connection.”

USEFUL LINKS:Buy "The Gut-Immune Connection" by Emeran Mayer
[https://linktr.ee/mindandmatter_books]

Sign up for the weekly Mind & Matter newsletter
[https://mindandmatter.substack.com/]

Follow & Support Nick's work
[https://linktr.ee/trikomes]Download the podcast & follow Nick at his website
[https://www.nickjikomes.com/]

Support the show on Patreon & get early access to episodes
[https://www.patreon.com/nickjikomes]

Athletic Greens, comprehensive daily nutrition (Free 1-year supply of Vitamin D w/ purchase)
[https://www.athleticgreens.com/mindandmatter]

Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
[https://readwise.io/nickjikomes/]

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​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to Jon Kostakopoulos, an early participant in an NYU study looking at psilocybin for the treatment of alcoholism. Jon went through psilocybin-assisted psychotherapy over the course of many weeks for this study, which included three separate days of psilocybin administration. He talked about his battle with alcoholism leading up to the study, how he was recruited to the study, and what his psilocybin experiences were like. He also shared what he has been doing since his psilocybin experiences, including founding Apollo Pact, a non-profit working to advance research into the therapeutic potential of psilocybin.

USEFUL LINKS
Sign up for the weekly Mind & Matter newsletter
[https://mindandmatter.substack.com/]

Download the podcast & follow Nick at his website
[https://www.nickjikomes.com]

Buy books by M&M guests
[https://linktr.ee/mindandmatter_books]

Athletic Greens, comprehensive daily nutrition (Free 1-year supply Vitamin D w/ purchase)
[https://athleticgreens.com/partner/d3...]

Organize your digital highlights & notes w/ Readwise (2 months free w/ sub)
[https://readwise.io/nickjikomes/]

Follow & Support Nick's work
[https://linktr.ee/trikomes]

Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to neuroscientist and machine learning engineer, Alex Wiltschko, PhD. Alex is a senior scientist at Google Brain, where he leads the digital olfaction group, where are working to build machines with a sense of smell. Alex received a PhD in neurobiology from Harvard, where he developed sophisticated machine vision and machine learning techniques to study animal behavior. They discussed Alex's research, the neuroscience of olfactory perception and animal behavior, as well as Alex's thoughts on topics related to machine learning and artificial intelligence.

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Sign up for the weekly Mind & Matter newsletter
[https://mindandmatter.substack.com/]

Download the podcast & follow Nick at his website
[https://www.nickjikomes.com]

Buy books by M&M guests
[https://linktr.ee/mindandmatter_books]

Athletic Greens, comprehensive daily nutrition (Free 1-year supply Vitamin D w/ purchase)
[https://athleticgreens.com/partner/d3...]

Organize your digital highlights & notes w/ Readwise (2 months free w/ sub)
[https://readwise.io/nickjikomes/]

Follow & Support Nick's work
[https://linktr.ee/trikomes]

Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S.

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to science writer and NYT columnist Carl Zimmer about his new book, "Life's Edge: The Search For What It Means To Be Alive." They discuss the scientific quest to understand life: what is it, how does it arise, and how might scientists identify it elsewhere in the universe? They also discuss Carl's approach to science writing, including where he draws inspiration and what his writing process looks like.

USEFUL LINKS:Download the podcast & follow Nick at his website
[www.nickjikomes.com]

Support the show on Patreon & get early access to episodes
[https://www.patreon.com/nickjikomes]

Sign up for the weekly Mind & Matter newsletter
[http://eepurl.com/hFlc7H]

Try MUD/WTR, a mushroom-based coffee alternative
[https://www.mudwtr.com/mindmatter]
Discount Code ($5 off) = MINDMATTER

Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
[https://readwise.io/nickjikomes/]

Start your own podcast (get $20 Amazon gift card after signup)
[https://www.buzzsprout.com/?referrer_id=1507198]

Buy Mind & Matter T-Shirts
[https://www.etsy.com/shop/OURMIND?ref=simple-shop-header-name&listing_id=1036758072§ion_id=34648633]

Connect with Nick Jikomes on Twitter
[https://twitter.com/trikomes]
​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to biological anthropologist and cognitive scientist, Terrence Deacon. The conversation focuses on ideas from Terrence's book, "The Symbolic Species: The Co-Evolution of Language and the Brain." They spend nearly three hours talking about the origins of language. Topics include: what is language and how does it differ from animal communication? How do children acquire language so easily at a young age? What is symbolic cognition, how is it different from other forms of cognition, and how did this unlock our ability to evolve language?

USEFUL LINKS
Sign up for the weekly Mind & Matter newsletter
[https://mindandmatter.substack.com/]

Download the podcast & follow Nick at his website
[https://www.nickjikomes.com]

Buy books by M&M guests
[https://linktr.ee/mindandmatter_books]

Athletic Greens, comprehensive daily nutrition (Free 1-year supply Vitamin D w/ purchase)
[https://athleticgreens.com/partner/d3...]

Organize your digital highlights & notes w/ Readwise (2 months free w/ sub)
[https://readwise.io/nickjikomes/]

Follow & Support Nick's work
[https://linktr.ee/trikomes]

Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to Dr. Yasmin Hurd, a neuroscientist studying medical cannabis, CBD, and opioid addiction. Dr. Hurd is investigating the ability of CBD to help treat withdrawal symptoms and prevent relapse in opioid-addicted individuals.

USEFUL LINKS
Sign up for the weekly Mind & Matter newsletter
[https://mindandmatter.substack.com/]

Download the podcast & follow Nick at his website
[https://www.nickjikomes.com]

Buy books by M&M guests
[https://linktr.ee/mindandmatter_books]

Athletic Greens, comprehensive daily nutrition (Free 1-year supply Vitamin D w/ purchase)
[https://athleticgreens.com/partner/d3...]

Organize your digital highlights & notes w/ Readwise (2 months free w/ sub)
[https://readwise.io/nickjikomes/]

Follow & Support Nick's work
[https://linktr.ee/trikomes]

Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to genetic engineer Alina Chan, PhD. She is working on engineering new forms of gene therapy using viral vectors to target diverse patient populations. In addition to her core scientific focus, Alina has recently investigated genomic data related to SARS-CoV-2, the virus responsible for the COVID19 pandemic.

They discuss the basics of virus biology, including what kind of virus SARS-CoV-2 is and how it infects human cells. They also talked about the published research on this virus that has come out in the past year, Alina's recent investigations into the origins of this virus and why it’s crucial for humanity to understand exactly how this virus originated, as well as new variants that have emerged, and where this virus might be going.

USEFUL LINKS
Sign up for the weekly Mind & Matter newsletter
[https://mindandmatter.substack.com/]

Download the podcast & follow Nick at his website
[https://www.nickjikomes.com]

Buy books by M&M guests
[https://linktr.ee/mindandmatter_books]

Athletic Greens, comprehensive daily nutrition (Free 1-year supply Vitamin D w/ purchase)
[https://athleticgreens.com/partner/d3...]

Organize your digital highlights & notes w/ Readwise (2 months free w/ sub)
[https://readwise.io/nickjikomes/]

Follow & Support Nick's work
[https://linktr.ee/trikomes]

Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcas

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to Dr. Michael Eisen, a biologist at UC-Berkeley and editor-in-chief for eLife, a non-profit open access science journal. Throughout his career, Dr. Eisen has been an advocate of open science, the free release of the results of scientific research, and has been critical of traditional forms of scientific publishing, which often place scientific results behind a paywall.

They discuss a variety of topics related to how academic science is conducted, including how it gets funded and what is involved in running a research lab. Much of the discussion centers on the business of scientific publishing, including what scientific journals are and their history, as well as the business models of for-profit journals and how they work. They also talk about open access journals and new ways that people are using technology to get around paywalls.

Scientific publishing is an industry that most people have little awareness of (including many scientists), and the size and profitability of large scientific publishing groups may surprise you.

USEFUL LINKS:Download the podcast & follow Nick at his website
[www.nickjikomes.com]

Support the show on Patreon & get early access to episodes
[https://www.patreon.com/nickjikomes]

Sign up for the weekly Mind & Matter newsletter
[http://eepurl.com/hFlc7H]

Try MUD/WTR, a mushroom-based coffee alternative
[https://www.mudwtr.com/mindmatter]
Discount Code ($5 off) = MINDMATTER

Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
[https://readwise.io/nickjikomes/]

Start your own podcast (get $20 Amazon gift card after signup)
[https://www.buzzsprout.com/?referrer_id=1507198]

Buy Mind & Matter T-Shirts
[https://www.etsy.com/shop/OURMIND?ref=simple-shop-header-name&listing_id=1036758072§ion_id=34648633]

Connect with Nick Jikomes on Twitter
[https://twitter.com/trikomes]
​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to Dr. Bob Stickgold, a cognitive neuroscientist and sleep expert. Dr. Stickgold is a professor of psychiatry at Harvard Medical School and has been studying sleep, dreams, and memory for over 25 years.

They discuss a variety of sleep topics, included sleep architecture and why there are different stages of sleep; the relationship between sleep stages and memory; how different drugs and disease states relate to sleep; how sleep differs as we develop and between species. Dr. Stickgold also shares various sleep-related health tips, including why it's important to get adequate sleep when you get vaccinated.

Sign up for the weekly Mind & Matter newsletter
[https://mindandmatter.substack.com/?sort=top]

Follow Nick's work through Linktree:
[https://linktr.ee/trikomes]

Athletic Greens, comprehensive daily nutrition (Free 1-year supply Vitamin D w/ purchase)
[https://www.athleticgreens.com/mindandmatter]

Try Levels Health to monitor your blood sugar & optimize your diet
[https://www.levelshealth.com/join?partner=MINDANDMATTER]

Organize your digital highlights & notes w/ Readwise (2 months free w/ sub)[https://readwise.io/nickjikomes/]

Try MUD/WTR, a mushroom-based coffee alternative
[https://www.mudwtr.com/mindmatter]
Discount Code ($5 off) = MINDMATTER

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

View Details

This bonus episode is a lecture given by mushroom expert Dr. Michael Beug (probably from the 1980s). Professor Beug describes the results of his work analyzing the chemical contents of various psilocybin-containing ("magic") mushrooms native to the Pascific Northwest. You'll learn some interesting observations about different Psilocybe mushrooms, including how psilocybin content varies across species, and which species tend to be the most potent.

USEFUL LINKS:
Sign up for the weekly Mind & Matter newsletter
[http://eepurl.com/hFlc7H]

Try MUD/WTR, a mushroom-based coffee alternative
[https://www.mudwtr.com/mindmatter]
Discount Code ($5 off) = MINDMATTER

Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
[https://readwise.io/nickjikomes/]

Buy Mind & Matter T-Shirts
[https://www.etsy.com/shop/OURMIND?ref=simple-shop-header-name&listing_id=1036758072§ion_id=34648633]

Connect with Nick Jikomes on Twitter
[https://twitter.com/trikomes]
​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

View Details

Dr. Ziva Cooper, Director of the UCLA Cannabis Research Initiative, discusses the latest medical cannabis research. She goes into everything from the potential interactive of effects of cannabinoids and terpenes, to the efficacy of cannabidiol (CBD), to sex- and age-dependent differences in how cannabinoids affect the body.

USEFUL LINKS:Download the podcast & follow Nick at his website
[www.nickjikomes.com]

Support the show on Patreon & get early access to episodes
[https://www.patreon.com/nickjikomes]

Sign up for the weekly Mind & Matter newsletter
[http://eepurl.com/hFlc7H]

Try MUD/WTR, a mushroom-based coffee alternative
[https://www.mudwtr.com/mindmatter]
Discount Code ($5 off) = MINDMATTER

Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
[https://readwise.io/nickjikomes/]

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Buy Mind & Matter T-Shirts
[https://www.etsy.com/shop/OURMIND?ref=simple-shop-header-name&listing_id=1036758072§ion_id=34648633]

Connect with Nick Jikomes on Twitter
[https://twitter.com/trikomes]
​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick Jikomes talks to Jeff Ubersax, PhD, CEO of the biotechnology company Demetrix (who supported this episode). Jeff discussed the science behind how Demetrix is engineering baker's yeast to produce cannabinoids at an industrial scale, with a focus on making rare cannabinoids other than THC and CBD.

Jeff also discussed how he transitioned from academic science to running his own company, and offered advice for academic scientists in training who might be thinking about moving into biotechnology.

Episode Support: This episode was supported by Demetrix, a biotechnology company using cutting edge fermentation technology to produce rare cannabinoids that are safe, legal, and effective for health and wellness.

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Athletic Greens, comprehensive daily nutrition (Free 1-year supply Vitamin D w/ purchase)
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Organize your digital highlights & notes w/ Readwise (2 months free w/ sub)
[https://readwise.io/nickjikomes/]

Follow & Support Nick's work
[https://linktr.ee/trikomes]

Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to Elizabeth Hobson, PhD, whose lab studies the evolution of decision-making, social cognition, social networks, and dominance hierarchies using a combination of naturalistic field observations of animal behavior combined with computational modeling and network analysis.

They discuss social behavior in animals, including when and why members of a group display aggression, how animal dominance hierarchies form and change, and how changes in the environment can cause sudden “tipping points” where group behavior suddenly changes. We also discussed whether human societies may be near tipping points today, and how changes due to COVID have impacted remote learning.

USEFUL LINKS:Download the podcast & follow Nick at his website
[www.nickjikomes.com]

Support the show on Patreon & get early access to episodes
[https://www.patreon.com/nickjikomes]

Sign up for the weekly Mind & Matter newsletter
[http://eepurl.com/hFlc7H]

Try MUD/WTR, a mushroom-based coffee alternative
[https://www.mudwtr.com/mindmatter]
Discount Code ($5 off) = MINDMATTER

Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
[https://readwise.io/nickjikomes/]

Start your own podcast (get $20 Amazon gift card after signup)
[https://www.buzzsprout.com/?referrer_id=1507198]

Buy Mind & Matter T-Shirts
[https://www.etsy.com/shop/OURMIND?ref=simple-shop-header-name&listing_id=1036758072§ion_id=34648633]

Connect with Nick Jikomes on Twitter
[https://twitter.com/trikomes]
​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to theoretical physicist Geoffrey West about the universal scaling laws that describe how organisms, companies, and cities grow and die.

USEFUL LINKS:Buy "Scale" by Geoffrey West
[https://linktr.ee/mindandmatter_books]

Sign up for the weekly Mind & Matter newsletter
[https://mindandmatter.substack.com/]

Follow & Support Nick's work
[https://linktr.ee/trikomes]Download the podcast & follow Nick at his website
[https://www.nickjikomes.com/]

Support the show on Patreon & get early access to episodes
[https://www.patreon.com/nickjikomes]

Athletic Greens, comprehensive daily nutrition (Free 1-year supply of Vitamin D w/ purchase)
[https://www.athleticgreens.com/mindandmatter]

Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
[https://readwise.io/nickjikomes/]

Start your own podcast (get $20 Amazon gift card after signup)
[https://www.buzzsprout.com/?referrer_id=1507198]

Buy Mind & Matter T-Shirts
[https://www.etsy.com/shop/OURMIND?ref=simple-shop-header-name&listing_id=1036758072§ion_id=34648633]
​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

View Details

Nick talks to Dr. Matthew Hill about the role of the endocannabinoid system in regulating stress and emotional behavior. They also discuss how plant cannabinoids from Cannabis, such as THC and CBD, impact the endocannabinoid system.

USEFUL LINKS:Download the podcast & follow Nick at his website
[www.nickjikomes.com]

Support the show on Patreon & get early access to episodes
[https://www.patreon.com/nickjikomes]

Sign up for the weekly Mind & Matter newsletter
[http://eepurl.com/hFlc7H]

Try MUD/WTR, a mushroom-based coffee alternative
[https://www.mudwtr.com/mindmatter]
Discount Code ($5 off) = MINDMATTER

Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
[https://readwise.io/nickjikomes/]

Start your own podcast (get $20 Amazon gift card after signup)
[https://www.buzzsprout.com/?referrer_id=1507198]

Buy Mind & Matter T-Shirts
[https://www.etsy.com/shop/OURMIND?ref=simple-shop-header-name&listing_id=1036758072§ion_id=34648633]

Connect with Nick Jikomes on Twitter
[https://twitter.com/trikomes]
​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

View Details

Nick talks to paleoanthropologist John Hawks about the story of human evolution.

USEFUL LINKS:
Sign up for the weekly Mind & Matter newsletter
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Download the podcast & follow Nick at his website
[https://www.nickjikomes.com]

Buy books by M&M guests
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Athletic Greens, comprehensive daily nutrition (Free 1-year supply of Vitamin D w/ purchase)
[https://athleticgreens.com/partner/d3...]

Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
[https://readwise.io/nickjikomes/]

Follow & Support Nick's work
[https://linktr.ee/trikomes]

Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Nick talks to neurologist and plant medicine expert Dr. Ethan Russo about medical cannabis and related topics, such as cannabinoids (e.g. THC, CBD, CBG, THCV), terpenes (myrcene, limonene, beta-caryophyllene), endocannabinoid biology, and Ethan's thoughts on the legal cannabis industry, including whether the terms "Indica" and "Sativa" are meaningful.

USEFUL LINKS:Download the podcast & follow Nick at his website
[www.nickjikomes.com]

Support the show on Patreon & get early access to episodes
[https://www.patreon.com/nickjikomes]

Sign up for the weekly Mind & Matter newsletter
[http://eepurl.com/hFlc7H]

Try MUD/WTR, a mushroom-based coffee alternative
[https://www.mudwtr.com/mindmatter]
Discount Code ($5 off) = MINDMATTER

Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
[https://readwise.io/nickjikomes/]

Start your own podcast (get $20 Amazon gift card after signup)
[https://www.buzzsprout.com/?referrer_id=1507198]

Buy Mind & Matter T-Shirts
[https://www.etsy.com/shop/OURMIND?ref=simple-shop-header-name&listing_id=1036758072§ion_id=34648633]

Connect with Nick Jikomes on Twitter
[https://twitter.com/trikomes]
​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick talks to neuropsychologist Katrin Preller, PhD about psychedelics like LSD and psilocybin, empathogens like MDMA, and stimulants like cocaine. Katrin explains how each type of drug affects the brain differently and what that means for their impact on empathy, social cognition, and their addictive potential.

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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick talks to Peter Addy, PhD about the atypical, dissociative psychedelic, salvia. Peter is a psychotherapist and spent several years at the Yale, studying human experiences with atypical psychedelics such as Salvia divinorum.

Nick and Peter talked about salvia, including how it works and how it differs from other psychedelics, as well as dissociative and dysphoric effects, and how his research has informed his psychotherapy practice.

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[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Nick talks to Hamilton Morris, creator of the show, "Hamilton's Pharmacopeia," currently in its third and final season. They discuss the newest season of his show, including the content itself and what it took to actually make the show. They also talked about a variety of drugs and their effects, ranging from methamphetamine and ketamine, to various forms of DMT, to ibogaine and xenon gas.

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Elysium Health, a life sciences company focused on aging research. Use code MIND for 10% off first purchase of any of their supplement products. Valid until 6/22/2022.
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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Jonathan Page, PhD is a botanist and entrepreneur with deep expertise in Cannabis. Nick and Jon talked about all things Cannabis science including the botany and natural history of Cannabis, the chemistry and biology of Cannabis and its psychoactive effects, and whether or not different types of Cannabis can cause different effects. Jon also shared amazing stories about transitioning from scientific research to starting, building, and selling a cannabis company, and his thoughts on what’s next for the cannabis industry.

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​​

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

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Bryan Roth, MD, PhD discusses his career studying how psychedelics and other psychoactive drugs affect the brain, the massive $27 million research effort he is leading to understand psychedelics and develop novel drugs for psychiatric disease, and the practice of zen meditation.

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Follow & Support Nick's work
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Athletic Greens, comprehensive daily nutrition (Free 1-year supply of Vitamin D w/ purchase)
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​​​
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ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Sean B. Carroll, PhD is an award-winning biologist, author, and filmmaker. Nick and Sean discuss everything from Sean's unique career trajectory and writing process, to dinosaurs and snake venom, to COVID19, the evolution of viruses, and why comedians and scientists are kindred spirits.

USEFUL LINKS:Buy "A Series of Fortunate Events" by Sean B. Carroll
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Follow & Support Nick's work
[https://linktr.ee/trikomes]Download the podcast & follow Nick at his website
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Support the show on Patreon & get early access to episodes
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Athletic Greens, comprehensive daily nutrition (Free 1-year supply of Vitamin D w/ purchase)
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Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
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​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Dr. Nichols is a professor of pharmacology at Louisiana State University. He has been studying the molecular, genetic, and behavioral effects of psychedelics for nearly 25 years and is considered one of the world’s top experts on the biological effects of psychedelics in the brain and body.

Nick spoke to Charles for almost two hours, covering a wide range of topics related to how psychedelics work. They discuss everything from how psychedelics impact the serotonin system in the brain, the similarities and differences between drugs like psilocybin and ketamine, how microdosing specific psychedelics can lead to potent anti-inflammatory effects, and much more.

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Follow & Support Nick's work
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Support the show on Patreon & get early access to episodes
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Athletic Greens, comprehensive daily nutrition (Free 1-year supply of Vitamin D w/ purchase)
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Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
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​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]

ABOUT Nick Jikomes:
Nick is a neuroscientist and podcast host. He is currently Director of Science & Innovation at Leafly, a technology startup in the legal cannabis industry. He received a Ph.D. in Neuroscience from Harvard University and a B.S. in Genetics from the University of Wisconsin-Madison.

Support the show (https://www.patreon.com/nickjikomes)

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Brian is the author of the New York Times-bestselling book, "The Immortality Key: The Secret History of the Religion With No Name." Brian is fluent in Ancient Greek, Latin, and Sanskrit, and spent over a decade putting together an incredible story about the intentional use of psychoactive plants in the ancient world, including scientific evidence for the ritual use of spiked beers and wines.

Nick and Brian cover topics related to his book, including the use of psilocybin mushrooms in the present to treat end of life anxiety, how “Mystery Schools” in the ancient Greco-Roman world, such as Eleusis, may have utilized psychedelic beverages, the evidence for the potential widespread use of psychoactive plants in ritual settings in ancient times, and how this may have influenced early Christianity, and how psychedelic drugs may induce brain states similar to those produced in near-death experiences.
USEFUL LINKS:Buy "The Immortality Key" by Brian Muraresku
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Follow & Support Nick's work
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Support the show on Patreon & get early access to episodes
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Athletic Greens, comprehensive daily nutrition (Free 1-year supply of Vitamin D w/ purchase)
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Organize your digital highlights & notes w/ Readwise (2 months free w/ subscription)
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Start your own podcast (get $20 Amazon gift card after signup)
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​​​
Learn more about our podcast sponsor, Dosist
[https://dosist.com/]