Dive into Ketamine's incredible versatility! This episode explores how tailoring ketamine dosing strategies is key to unlocking its potential across a surprisingly wide range of conditions, from severe depression to pain management. Learn why it's considered a "reset button" for disrupted brain pathways due to its unique action on NMDA receptors, leading to rapid anti-depressant effects often within hours.

The episode highlights the crucial need for individualized treatment plans, emphasizing that the optimal dose and delivery method — whether intravenous, intramuscular, or subcutaneous — vary greatly depending on the patient's age, weight, other medical conditions, and even co-occurring medications. Discover why it's not simply a case of "more is better," with moderate, subanesthetic doses often proving most effective for depression in an "inverted U-shaped" dose-response curve. Understand how repeated infusions can lead to longer-lasting benefits beyond a single dose, making it a promising option for sustained relief in treatment-resistant cases.

This deep dive underscores that ketamine is a powerful tool that requires expert handling and careful monitoring to balance its remarkable therapeutic potential with potential risks and side effects.

Based on the 2025 review: Optimizing Ketamine Dosing Strategies across Diverse Clinical Applications: A Comprehensive review. [http://dx.doi.org/10.1097/MS9.0000000000003580]

Tune into Talking Ketamine, Episode 23: Ketamine & Neuroethics, for a mind-bending exploration. We delve into how ketamine's unique altered states of consciousness, like ego dissolution and dissociation, could serve as a blueprint for future brain-computer interfaces. This episode reveals how neurochemistry might inspire technology to design new modes of consciousness, going beyond simply repairing the brain to potentially enhancing or redesigning consciousness itself.

Learn more from the study discussed: "Neurochemical Horizons: Elon Musk, Ketamine, and the Future of Neural Interface Design" (DOI: 10.13140/RG.2.2.20903.05287) - https://www.researchgate.net/publication/392269296_Neurochemical_Horizons_Elon_Musk_Ketamine_and_the_Future_of_Neural_Interface_Design

Dive into a fascinating single case study that spotlights the potential of sublingual ketamine troches for those battling tough mental health challenges. Discover how one patient with treatment-resistant depression, PTSD, and social anxiety disorder found significant relief and was able to reduce multiple medications. This episode unpacks a compelling real-world story, offering insights into ketamine's promise as a less invasive, accessible option for complex cases.

Find the study discussed in this episode here: https://doi.org/10.7759/cureus.87343

Welcome to "Talking Ketamine," Episode 21! Discover the fascinating world of Ketamine Assisted Therapy (KAT) and its promise for depression. We dive deep into **"set and setting"** – how your mindset and environment can profoundly transform the healing journey – all from the vital perspective of those who've experienced it. **Explore what truly makes for the best possible KAT experience.**

This episode draws insights from the new study, "Understanding the Experience of Ketamine-Assisted Therapy and the Importance of Context," by Grace Stockwell, Nicholas R. Hoeh, Francesca Fogarty, Cerys Clayden, and Lisa Reynolds, published in the Journal of Psychoactive Drugs on July 2nd, 2025.

Read the full study: https://doi.org/10.1080/02791072.2025.2527299

In this episode, we explore groundbreaking research on a formidable clinical challenge: co-occurring major depressive disorder (MDD) and opioid use disorder (OUD). A new randomized clinical trial compared adjunctive ketamine and buprenorphine, revealing significant reductions in both anxiety symptoms and craving intensity for patients with these co-occurring conditions. The study found that ketamine demonstrated a rapid reduction in anxiety and a pronounced decline in opioid craving within hours of administration. In contrast, buprenorphine was associated with a more gradual but sustained improvement in anxiety symptoms over several days, along with a modest initial reduction in opioid craving followed by persistent attenuation.

Tune in to understand these distinct treatment trajectories and the promising implications for managing this challenging patient population.

Read the full study by Mansoori et al. here: https://doi.org/10.1186/s13063-025-08836-4.

This episode tackles the profound challenge of treatment-resistant depression (TRD), a severe mental illness affecting 280 million people globally. While low-dose subanesthetic intravenous ketamine treatment has shown rapid improvement for TRD, its effects are often transient, lasting only days to weeks, and IV administration can be impractical and expensive for long-term use.

We shift focus to a novel, more accessible approach: very low-dose subcutaneous ketamine. Drawing on a unique case report, we explore its potential as a maintenance option for severe TRD. This method is highlighted for being less invasive, more cost-effective, practical, and accessible, potentially offering a more gradual absorption that could decrease adverse effects. The case study featured a patient with severe TRD who, after 15 years of struggle, achieved a stable mental state and maintained occupational functioning for four years with subcutaneous ketamine.

Study discussed: https://onlinelibrary.wiley.com/doi/10.1002/ccr3.6675

Explore a groundbreaking single case study from 2025 on ketamine-assisted psychotherapy (KAP) for the notoriously challenging anorexia nervosa (AN). Discover how KAP, coupled with Acceptance and Commitment Therapy (ACT), potentially creates a "neuroplastic window" for change in rigid thought patterns. The case study reveals marked symptom reduction in AN pathology, depression, and anxiety, alongside improved quality of life for one patient. This unique case highlights the critical synergy between ketamine and therapy for sustained gains, while also navigating complexities like post-treatment weight loss and a subsequent psilocybin experience. It's a powerful glimpse of hope for treatment-resistant conditions, demanding further rigorous research.

Find the full report here: https://jeatdisord.biomedcentral.com/articles/10.1186/s40337-025-01313-y

Dive into the incredible, 60-year saga of ketamine! Our deep dive explores the fascinating journey of this molecule, originally known as CI-581, from its origins as an 'older sibling' to PCP (phencyclidine). Discover how it became the subject of the first-in-human study for a novel anesthetic. Learn about its unique status as the only "dissociative anesthetic", noted for rapid onset, short duration, and minimal adverse cardiovascular or respiratory effects, yet also for its distinct psychic "syndrome" that led to the term "dissociative anesthesia".

Explore how ketamine faced controversy and fell out of favor due to psychotomimetic effects and patient nightmares, only to experience a "rebirth" through scientific understanding of its NMDA receptor antagonism and the use of benzodiazepines to mitigate side effects. Witness its dramatic resurgence in anesthesiology and pain management, driven by the opioid crisis, making opioid-sparing anesthesia ubiquitous.

Most recently, delve into its "explosive" life as a rapid-acting antidepressant, a discovery that has revolutionized psychiatry and led to the FDA approval of S(+)-ketamine nasal spray. Ketamine's story highlights its pharmacologic complexity and its role as a "pharmacologic agent provocateur", challenging classical drug development paradigms by showing effects that "outlast" plasma exposure. This powerful journey raises critical questions about modern drug discovery and whether such a complex molecule would even be approved today.

Learn more in the insightful commentary that guided this episode: The Nine Lives of Ketamine from CI-581 to Present Day Clinical Application—Commentary on Domino et al. by Evan D. Kharasch, published in Clinical Pharmacology and Therapeutics. Link to the study: https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.3634

Uncover a crucial, rarely discussed topic in Episode 16 of 'Talking Ketamine': the potential effects of ketamine on sexual health. We delve into a 2023 systematic review by Pominville et al., which, after an extensive search, included only four studies. These limited findings, primarily from studies of illicit, heavy, long-term ketamine use, suggest a potential correlation with sexual dysfunction. This episode critically highlights a significant research gap regarding medical ketamine use. Tune in to understand what the current, albeit limited, science indicates and why more research is urgently needed in clinical populations.

Link to the systematic review discussed:

Pominville, R., Loria, M., Fraiman, E., & Mishra, K. (2023). Sexual Dysfunction Related to Ketamine Use: a Systematic Review. Current Sexual Health Reports, 15(4), 125–131. https://doi.org/10.1007/s11930-023-00363-0.

Ketamine therapy is increasingly explored for mental health, but what about the potential risks? In this crucial episode, we delve into the landscape of ketamine use disorder, drawing on insights from a significant 2025 study based on the direct experiences of 274 individuals with KUD.

Learn about the common physical warning signs reported by people with KUD, including prevalent bladder and nasal problems, and the intense 'K-cramps'. Discover the challenging abstinence and withdrawal symptoms they experienced when trying to cut back or stop, such as intense cravings, low mood, and anxiety.

The episode also highlights a striking finding: the significant lack of awareness among users, peers, and even professionals regarding ketamine's risks and addictive potential.

Whether you're considering or currently undergoing ketamine therapy, this episode provides vital information on signs to look out for and underscores the importance of open conversations with healthcare providers to navigate this treatment both effectively and safely.

Read the study discussed in this episode: https://doi.org/10.1111/add.70073