Ketamine vs. Psilocybin for Depression: A Clinical Comparison
About This Video
A clinical psychopharmacologist compares ketamine and psilocybin for depression treatment, covering mechanism of action, onset speed, duration of effect, access, and patient selection. The comparison is grounded in clinical evidence rather than advocacy for either approach. Key points: ketamine's NMDA antagonism produces effects within hours (critical for acute suicidality) while psilocybin's serotonin 2A agonism produces effects that may take weeks to fully emerge but can last months or years after a single session. Ketamine typically requires maintenance dosing; psilocybin in trials often does not. The video is unusually balanced — acknowledging that both have evidence and that neither is universally superior, and that the question is which approach is best for which patient and situation.
Key Takeaways
- Ketamine acts within hours (NMDA antagonism); psilocybin effects emerge over days to weeks (serotonin 2A agonism).
- Duration: ketamine effects last days-weeks per treatment; psilocybin effects can last months-years after 1-2 sessions.
- Access: ketamine is FDA-approved and widely available; psilocybin is legal only in Oregon and Colorado.
- Patient selection matters: ketamine for acute crisis; psilocybin for patients who can engage in psychological work.
- The two are not substitutes for each other — they address overlapping but distinct clinical needs.
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