Mind & Matter

• 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 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. Use code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off For all the ways you can support my efforts

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• Linoleic Acid, Seed Oils, mTOR & Breast Cancer | Nikos Koundouros & John Blenis | 229

  Send us a textEpisode 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 & GaneSupport 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. Use code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off For all the ways you can support my efforts

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• Rhythms, Memory, Time, Place, Representation & the Brain | György Buzsáki | 228

  Send us a textEpisode 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.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. Use code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off For all the ways you can support my efforts

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• Biophysics of Life: Biophotons, Light, Quantum Biology, Regeneration & Cancer | Nirosha Murugan | 227

  Send us a textThe 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.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. Use code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off For all the ways you can support my efforts

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• Psychedelics & Cerebral Cortex: Neuroplasticity, Psilocybin, Ketamine | Alex Kwan | 226

  Send us a textShort 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.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. Use code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off For all the ways you can support my efforts

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