Talking Ketamine Podcast

Talking Ketamine
  • 4.3 (11)
  • MENTAL HEALTH
  • UPDATED WEEKLY

Explore the cutting-edge science and therapeutic potential of ketamine. Talking Ketamine offers evidence-based discussions to demystify its role in mental health and beyond, providing informed insights into this powerful compound.

  1. Ketamine as Therapy Multiplier?

    21H AGO

    Ketamine as Therapy Multiplier?

    In episode 53, we move out of the sterile lab and into the messy real world, examining a large naturalistic study of 224 patients from an Austin clinic. The paper by Kosted and colleagues compares standard "infusion-only" ketamine treatment against Ketamine-Assisted Therapy (KAT) to answer a costly question: is paying for a therapist to be in the room actually worth it? The average results were shocking: across the entire sample, the therapy group didn't fare any better than the infusion-only group. But when researchers sliced the data by age and Adverse Childhood Experiences (ACEs), a much more complex story emerged. We unpack the counterintuitive "super responder" effect, where patients with high childhood trauma saw the most dramatic biological healing. For young adults under 30, the medicine alone was often more effective, suggesting that talk therapy might actually interrupt the "bake" of neuroplasticity by shifting activity to the analytical brain too soon. Conversely, for patients over 50, therapy was essential; without a human connection to help navigate and rewire decades of compensatory behaviors, the ketamine alone often fell short. Finally, we discuss the practical implications of the "decelerating curve" of improvement—where the most dramatic drops in depression occur early in treatment—and why the future of personalized psychiatry must look beyond DNA to a patient's lived biography. Reference: Kosted, R., Waddell, A., Adolph, K., & Fonzo, G. A. (2026). Age-related moderation of adjunctive psychotherapy and early life stress effects on depression symptom reductions following ketamine treatment: Initial insights from a large, naturalistic sample. Journal of Affective Disorders, 402, 121350. https://doi.org/10.1016/j.jad.2026.121350

    16 min
  2. The Nine Year Odyssey

    FEB 12

    The Nine Year Odyssey

    For the podcast's one-year anniversary, we zoom out from single studies to examine a comprehensive masterpiece: the doctoral thesis of Jolien K.E. Veraart, representing nine years of research (2016–2026) at the University of Groningen. This document moves beyond the initial hype of "does it work?" to the mature, difficult questions of long-term maintenance and safety. We unpack the critical concept of auto-induction—the discovery that the liver eventually "learns" to metabolize ketamine so efficiently that stable doses stop working, creating a bioavailability trap that looks like relapse but is actually just enzymatic efficiency. The episode also tackles the "nightmare" of oral dosing, where absorption is so variable that it makes consistent treatment a roll of the dice. Finally, we discuss the philosophical shift in Veraart’s work: moving away from the "trip" as the cure and toward a model where ketamine simply "softens the clay" of the brain. This places the responsibility back on set and setting not just as a safety measure, but as the tool that sculpts the neuroplastic brain into a healthier shape. Reference: Veraart, J. K. E. (2026). Ketamine for depression: Moving from research to clinical practice [Doctoral thesis, University of Groningen]. https://doi.org/10.33612/diss.1484805904

    15 min
  3. The Nasal Spray Wars

    FEB 5

    The Nasal Spray Wars

    In the world of ketamine therapy, there is a distinct divide: the FDA-approved, insurance-covered "Gold Standard" (Esketamine/Spravato) versus the cheap, off-label generic (Racemic Ketamine). In this episode, we step into the ring to judge "The Nasal Spray Wars" using a groundbreaking 2026 meta-analysis by Bahji and colleagues published in the Journal of Affective Disorders. We break down the "skim milk vs. whole milk" pharmacology: Esketamine isolates just the S-isomer, while generic ketamine contains both the S and R isomers. Big Pharma argues the isolate is cleaner, but the data tells a different story. We reveal the study's stunning conclusion: there is no significant difference in symptom relief between the two. In fact, the "cheap" generic showed higher remission rates and lower dropout rates than its expensive counterpart. The discussion tackles the massive elephant in the room: accessibility. With Spravato costing thousands of dollars per month and requiring strict in-clinic monitoring, we ask if the "premium" price tag is buying better health or just a patent. We conclude with a verdict for patients paying out-of-pocket: choosing the generic isn't "settling"—it may actually be the more effective, and certainly the more sustainable, path to recovery. Reference: Sarlon, J., Thomi, D., Brühl, A. B., Liwinski, T., & Lang, U. E. (2026). Real-world comparison of intranasal racemic ketamine and esketamine in treatment-resistant depression: A retrospective observational study. Journal of Affective Disorders, 400, 121208. https://doi.org/10.1016/j.jad.2024.07.054

    11 min
  4. Ketamine and the Nanoscopic World

    JAN 29

    Ketamine and the Nanoscopic World

    For decades, we’ve imagined the synapse as a "chemical soup"—a messy place where one neuron sprays neurotransmitters at another, hoping for a connection. But in this milestone 50th episode, we use the lens of the groundbreaking book Nano-Organization of the Synapse to reveal the stunning reality: the synapse is actually a piece of high-precision Swiss watchmaking. We explore the revolution in super-resolution microscopy (like STORM and cryo-electron tomography) that has allowed us to see the nanocolumn—a dedicated architectural alignment where a presynaptic "launch pad" (controlled by the protein Munc13) sits perfectly opposite a postsynaptic "receiver slot" (held by PSD95). This "trans-synaptic alignment" ensures that every signal is a sniper shot, not a sprinkler spray. The episode dives into the three modes of transmission—synchronous (the fast lane), asynchronous (the stutter), and the critical spontaneous release (the "ghost in the machine"). We discuss the theory that depression is a failure of this nanoscopic geometry, where the "ghost" signal reinforces a broken state. Finally, we explain how ketamine acts as a rapid repair crew: by silencing the spontaneous noise at NMDA receptors, it triggers a panic-like "homeostatic plasticity" that forces the neuron to realign its columns, add more AMPA receptors (volume knobs), and restore the "liquid crystal" dance of the synapse. Reference: Kavalali, E. T. (Ed.). (2026). Nano-organization of the synapse: From structure to function (Vol. 48). Springer Nature Switzerland. https://doi.org/10.1007/978-3-032-12594-1

    10 min
  5. The Neuroplastic Revolution

    JAN 22

    The Neuroplastic Revolution

    For decades, the "Monoamine Dogma" ruled psychiatry: the brain was a chemical soup, depression was a lack of serotonin, and the cure was simply "filling the tank." But there was always a glitch in the matrix—why did it take weeks for pills to work if the chemistry changed in hours? In this special 25th-anniversary episode, we review a retrospective paper from 2026 that traces the history of the "Neuroplastic Revolution." We go back to the turning point: the accidental discovery that ketamine could stop depression in four hours, proving the problem wasn't a lack of fuel, but broken wiring. We unpack the science of structural repair: how ketamine blocks the "disappointment center" (the lateral habenula), wakes up the "construction foreman" (mTOR), and releases BDNF (Miracle-Gro for the brain) to physically regrow lost connections. We also look at the macro level, exploring how this "reboot" disrupts the Default Mode Network to stop the loop of rumination. Finally, we discuss where we are today in 2026: the age of Precision Psychiatry, where we stop guessing and start treating the specific biological cause—whether it’s inflammation, glutamate, or connectivity. Reference: Bulek, D., & BaDour, S. (2026). From monoamine deficits to multiscale plasticity: Twenty-five years of ketamine and the neurophysiology of depression. Journal of Neurophysiology. https://doi.org/10.1152/jn.00516.2025

    15 min
  6. Ketamine and Diabetes

    JAN 15

    Ketamine and Diabetes

    Patients with diabetes often face a brutal "syndemic"—a tangled web of chronic illness, Relentless nerve pain (neuropathy), and severe depression, all fueled by a common biological enemy: metabolic inflammation and Advanced Glycation End-products (AGEs). In this episode, we explore why ketamine, with its rapid antidepressant and non-opioid painkilling properties, looks like the perfect "two birds, one stone" solution on paper. But in practice, it requires walking a high-stakes "metabolic tightrope." We dive into the complex risks: The Glucose Rollercoaster: Ketamine can trigger a stress response that spikes blood sugar (hyperglycemia), yet in Type 1 diabetics, it has also been linked to dangerous, delayed drops (hypoglycemia). The Liver "Traffic Jam": In Type 2 diabetes, fatty liver disease can clog the body's filter, slowing down drug clearance and potentially turning a normal dose toxic. The Metformin Paradox: We discuss preclinical warnings that metformin—the most common diabetes drug—might actually blunt ketamine’s antidepressant effects. The solution? A move away from "one-size-fits-all" medicine toward Model-Informed Precision Dosing—using a patient’s kidney function, liver health, and genetics to calculate the perfect, safe dose. Reference: Sukhram, S. D., Sanchez, M., Anidugbe, A., Kupa, B., Edwards, V. P., Zia, M., & Yilmaz, G. (2026). Ketamine in diabetes care: Metabolic insights and clinical applications. Pharmaceutics, 18(1), 81. https://doi.org/10.3390/pharmaceutics18010081

    12 min
  7. The Patient's Voice

    JAN 8

    The Patient's Voice

    Clinicians measure success in symptom scores and receptor occupancy, but for patients with Treatment-Resistant Depression (TRD), success is defined by something far more personal: the return of connection, clarity, and "life." In this episode, we amplify the "Patient's Voice" through a comprehensive synthesis of qualitative studies by Walasek and colleagues. We trace the emotional arc of treatment, starting with the profound ambivalence of patients who see ketamine as a "last resort"—terrified it will be just another failure in a long line of disappointments. We then step inside the acute experience itself, often described as a "rollercoaster" where euphoria and panic can flip on a dime, making the safety of the setting and the empathy of the staff critical to preventing trauma. The discussion challenges the medical model's obsession with dissociation as a measurable "active ingredient," revealing that patients value the meaning they make of the experience—the moments of insight and emotional release—far more than the intensity of the "trip" itself. Finally, we expose the hidden barriers to care: the crushing financial burden, the stigma of using a "party drug," and the finding that patients often attribute up to 50% of their therapeutic outcome not to the molecule, but to the kindness and support of the clinical staff.

    9 min
  8. The Science of Dissociation

    12/31/2025

    The Science of Dissociation

    For decades, the "trip" caused by ketamine—sensory detachment, time warping, and out-of-body experiences—was seen as a nuisance, a "bug" to be tolerated during anesthesia. But a groundbreaking 2025 review paper by Berra and colleagues asks a provocative question: What if dissociation is actually the point? In this episode, we dive into the "Science of Dissociation," exploring the spectrum from simple "checking out" (daydreaming) to profound depersonalization and derealization. We analyze the "switch" in the brain—how ketamine blocks NMDA receptors on inhibitory interneurons, unleashing a glutamate burst that disrupts the Default Mode Network (DMN). This disruption forces the brain into a "chaotic" state of higher entropy, breaking rigid, depressive thought loops and allowing the mind to form new, healthier connections. We also look to the future of "non-hallucinogenic" alternatives like hydroxynorketamine (HNK), which promote neuroplasticity without the trip. This raises a fundamental philosophical and clinical question: Is the conscious experience of an altered state the "price of admission" for healing, or can we bypass the mind to fix the brain? Reference: Bera, K., Looger, L. L., Proekt, A., & Cichon, J. (2025). Cortical mechanisms contributing to ketamine-induced dissociation. The Neuroscientist, 1–17. https://doi.org/10.1177/10738584251403946

    11 min
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4.3
out of 5
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About

Explore the cutting-edge science and therapeutic potential of ketamine. Talking Ketamine offers evidence-based discussions to demystify its role in mental health and beyond, providing informed insights into this powerful compound.

Information

  • Creator
    Talking Ketamine
  • Years Active
    2024 - 2026
  • Episodes
    53
  • Rating
    Clean
  • Copyright
    © 2025 Talking Ketamine
  • Show Website
    Talking Ketamine Podcast

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