In this episode, we sit down again with Dr. Matthew Mosquera, a Harvard-trained addiction psychiatrist, for a deep dive into ketamine treatment — from its surprising history to its emerging role in mental health care. We kick things off by clearing up common misconceptions. While ketamine’s party-drug reputation persists, we explore its origins as a surgical anesthetic developed in the 1960s and how it rose to prominence during the Vietnam War. Its safety profile and effectiveness at sub-anesthetic doses have since made it a powerful tool in psychiatric care.

We focus on how ketamine works neurologically. It enhances neuroplasticity, helping the brain rewire and reconnect neural pathways damaged by depression and chronic stress. This restoration of “functional connectivity” enables emotional regulation to return more efficiently. Dr. Mosquera explains that ketamine doesn’t just mute symptoms like many SSRIs—it opens a short window where behavior and mindset shifts can take root more easily.

From there, we get into the logistics. Most patients begin with an “induction phase” — twice-weekly treatments for four weeks. Sessions typically last two hours and include an active dissociative phase followed by a recovery period. We learn that visuals, out-of-body sensations, and introspective insights are common but not guaranteed. Dr. Mosquera emphasizes the importance of environment and mindset in shaping each session’s impact. Clinics aim to create a calming, supportive space, and providers monitor patients throughout.

We also explore the differences between esketamine (the FDA-approved nasal spray for treatment-resistant depression) and generic ketamine, used off-label for conditions like PTSD, OCD, and anxiety. While esketamine is tightly regulated and covered by insurance, off-label use often involves out-of-pocket costs and different methods of administration like IV or IM injections.

Toward the end, we tackle common concerns: who shouldn’t use ketamine, potential side effects, and why at-home ketamine therapy can be risky. Dr. Mosquera offers cautious optimism about ketamine’s future, citing the growing data on long-term benefits. He encourages pairing treatment with therapy, movement, and other healthy habits for best results. We wrap with quick-hit facts and personal reflections, including Dr. Mosquera’s thoughts on why he was drawn to this field in the first place — and his belief in helping people reset when traditional treatments haven’t worked.

Reach out to Dr. Mosquera: [email protected]

00:00 - Intro
01:58 - What Is Ketamine? (History & Origins)
04:02 - Ketamine in Medical Use Today
05:02 - Ketamine for Depression Explained
06:28 - What is Esketamine vs. Ketamine?
08:29 - FDA Approvals and Other Mental Health Uses
09:38 - Off-Label Ketamine Use & Clinic Access
10:31 - Cost of Ketamine Treatment
13:00 - How Ketamine Helps the Brain (Neuroplasticity)
17:01 - What a Ketamine Treatment Session Feels Like
21:28 - Side Effects and How Patients Typically Feel After
22:34 - Ketamine-Assisted Psychotherapy (KAP)
25:15 - Psilocybin vs Ayahuasca vs Ketamine
28:16 - Who Shouldn’t Use Ketamine
30:13 - How Long Do the Effects Last?
32:49 - Matthew Perry’s Death & Ketamine Safety
34:51 - Ketamine Use Postpartum and While Breastfeeding
38:09 - What to Expect from Treatment
39:03 - Ketamine as a Party Drug & What Is a K-Hole?
42:56 - Long-Term Side Effects of Overuse
43:42 - The Future of Ketamine Clinics
44:55 - Fear of Psychedelics: Advice for First-Timers
47:05 - Fact or Fiction: Ketamine Myths Busted
48:44 - Frequency and Dosage Guidelines
50:59 - Where to Find Dr. Mosquera
51:22 - Outro and Closing Credits

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