Mind & Matter

• Psychoactive Drugs, Psychedelics, Society & Hamilton's Pharmacopeia | Hamilton Morris | 6

  Send us a textHamilton Morris discussing his documentary series on psychoactive drugs, their science, cultural impacts, and misconceptions.Topics Discussed:Origins of Hamilton's Pharmacopeia: Started as a column and web series to provide honest, science-based discussions on drugs, countering 1990s media stigma.Drug education and media bias: Traditional scare tactics fail; honest information fosters better relationships with substances, as seen in parallels with abstinence education.Methamphetamine misconceptions: Often stigmatized due to class differences, not pharmacology; similar to amphetamine, with FDA-approved uses for ADHD and obesity.Xenon gas as an anesthetic: A noble gas inducing euphoria via NMDA antagonism; harvested from air, it's expensive but potentially ideal for medical use.Ketamine and dissociatives: NMDA antagonists like ketamine offer rapid antidepressant effects; experiences are dose-dependent, from alcohol-like to visionary out-of-body states.Ibogaine in Bwiti rituals: Used for addiction treatment in Gabon; induces logical self-reflection, challenging Western views on psychedelics and spirituality.Drug regulation ideals: Advocate for freedom with quality controls, like food regulations; decriminalization alone lacks purity safeguards.Future projects: Shifting to chemistry research on psychedelics; highlights challenges in documentary production and value of synthesis education.*Not medical adviceSupport the showAffiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. Special sale Nov 10 - Dec 1: Lumen is half off ($599 → $299), and MINDMATTER gets another 15% off. AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, get $100 off for AquaTru Carafe, Classic and Under the Sink Units, and $300 off Freestanding models. Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) For all the ways you can support my efforts

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• Energy Metabolism & Information Processing in the Brain | Luis Felipe Barros | 264

  Send us a textIntegration 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.Support the showAffiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. Special sale Nov 10 - Dec 1: Lumen is half off ($599 → $299), and MINDMATTER gets another 15% off. AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, get $100 off for AquaTru Carafe, Classic and Under the Sink Units, and $300 off Freestanding models. Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) For all the ways you can support my efforts

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• How & Why Mitochondria Make Their Own Fat | Sara Nowinski | 263

  Send us a textMitochondrial 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 → ATPMitochondrial fatty acid synthesis (mitoFAS): a bacterial-like pathway that builds fats on an acyl carrier protein inside the matrixLipoic 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 useLonger mitoFAS products (14–16 carbons) stabilize electron transport chain assembly factors, explaining why pathway loss collapses respiration even when lipoic acid is intactKnocking 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 injuryMuscle cell differentiation fails without mitoFAS, hinting at a role in tissue development and repairPractical 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.Support the showAffiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. Special sale Nov 10 - Dec 1: Lumen is half off ($599 → $299), and MINDMATTER gets another 15% off. AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, get $100 off for AquaTru Carafe, Classic and Under the Sink Units, and $300 off Freestanding models. Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) For all the ways you can support my efforts

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• Hormones & Instincts: Hunger, Aggression & Parenting Behavior | Jonny Kohl | 262

  Send us a textHow internal states like hunger and hormones shape instinctive behaviors, particularly parental careEpisode 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 advSupport the showAffiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. Special sale Nov 10 - Dec 1: Lumen is half off ($599 → $299), and MINDMATTER gets another 15% off. AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, get $100 off for AquaTru Carafe, Classic and Under the Sink Units, and $300 off Freestanding models. Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) For all the ways you can support my efforts

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• Mitochondrial Transfer, Obesity & Immune-Metabolism Interactions | Jon Brestoff | 261

  Send us a textHow 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 transferRelated Episode:Support the showAffiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. Special sale Nov 10 - Dec 1: Lumen is half off ($599 → $299), and MINDMATTER gets another 15% off. AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, get $100 off for AquaTru Carafe, Classic and Under the Sink Units, and $300 off Freestanding models. Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app. KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime) For all the ways you can support my efforts

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