Mind & Matter

Send a text
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
Support the show
Health Products by M&M Partners:
SporesMD: Premium mushrooms products (gourmet mushrooms, nootropics, research). Use code 'nickjikomes' for 20% off.
Lumen device: Optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off.
AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $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

Send a text
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, Inflam
Support the show
Health Products by M&M Partners:
SporesMD: Premium mushrooms products (gourmet mushrooms, nootropics, research). Use code 'nickjikomes' for 20% off.
Lumen device: Optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off.
AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $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

Send a text
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
Support the show
Health Products by M&M Partners:
SporesMD: Premium mushrooms products (gourmet mushrooms, nootropics, research). Use code 'nickjikomes' for 20% off.
Lumen device: Optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off.
AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $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

Send a text
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.

Support the show
Health Products by M&M Partners:
SporesMD: Premium mushrooms products (gourmet mushrooms, nootropics, research). Use code 'nickjikomes' for 20% off.
Lumen device: Optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off.
AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $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

Send a text
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
Support the show
Health Products by M&M Partners:
SporesMD: Premium mushrooms products (gourmet mushrooms, nootropics, research). Use code 'nickjikomes' for 20% off.
Lumen device: Optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off.
AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $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