Ketamine is a dissociative anesthetic. At sub-anesthetic doses (intramuscular, intranasal, or sublingual), it has fast-onset antidepressant and anxiolytic effects.
Mechanism — NMDA receptor antagonism leads to a glutamate surge, increased BDNF, and new synaptic connections within 24 hours. Works on different timescale than SSRIs (hours vs weeks).
Use case — Treatment-resistant depression, PTSD, severe anxiety. Typical IM or IV course is 6 sessions over 2-3 weeks. Spravato (esketamine nasal spray) is the FDA-approved version.
Caveats — Recreational use risks bladder damage (ketamine cystitis), addiction, and tolerance. Therapeutic use requires monitored protocols. Set and setting matter — psychedelic-adjacent experiences benefit from preparation and integration.