Ketamine

Ketamine is a dissociative anesthetic that acts primarily as an NMDA receptor antagonist, producing rapid antidepressant effects through glutamate modulation and enhanced BDNF (brain-derived neurotrophic factor) production. Unlike classical psychedelics that work on serotonin receptors, ketamine's glutamate pathway allows it to work in patients taking SSRIs and produces effects within hours rather than weeks. Esketamine (Spravato), the S-enantiomer of ketamine, received FDA approval in 2019 for treatment-resistant depression when used with oral antidepressants, and in January 2025 gained approval as a monotherapy. Clinical studies show esketamine produces rapid improvement in depressive symptoms as early as 24 hours, with 22.5% achieving remission versus 7.6% on placebo. Ketamine clinics have proliferated across the United States, offering IV infusions, intramuscular injections, nasal spray, and lozenges for depression, anxiety, PTSD, and chronic pain. At-home ketamine services like Mindbloom and Nue Life have expanded access through telemedicine, with 35+ states now served. The ketamine experience at sub-anesthetic doses involves dissociation, altered time perception, and dreamlike states lasting 45-90 minutes. Research suggests ketamine's antidepressant effects stem from rapid synaptogenesis in the prefrontal cortex, essentially rebuilding neural connections weakened by chronic stress and depression.