Mind & Matter

• Brain Fat: Dietary PUFAs, Cannabinoids, Fatty Acid Binding Proteins, Anxiety & Mood | Steven Laviolette | 234

  Send us a textHow 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.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

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• Feel the Burn: Seed Oils, Memes & Oxidative Stress | Brian Kerley | 233

  Send us a textAre 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.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

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• SSRIs, Sexual Dysfunction, Suicide & Mass Shootings, How FDA Works | David Healy | 232

  Send us a textA 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.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

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• Psychedelic Chemistry, Magic Mushrooms, Kratom, Gray Market Research Chemicals, Vape Shops | Andrew Chadeayne | 231

  Send us a textEpisode 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.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

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

  Send us a textEpisode 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.Support the showAll episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts

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