Psilocybin
Active compound in "magic mushrooms"
FDA Breakthrough Therapy designation for treatment-resistant depression. Johns Hopkins, NYU, and Imperial College London studies show a single dose can produce significant, lasting reduction in depression and anxiety. Phase 3 trials ongoing (COMP360 by Compass Pathways, Usona Institute uAspire trial). 67% of participants in remission at 12 months in early studies.
Johns Hopkins, Imperial College London, NYU, Yale, COMPASS Pathways
Ayahuasca
DMT + MAO inhibitor plant brew
Traditional Amazonian medicine used for thousands of years. Contains DMT combined with an MAO inhibitor that allows oral absorption. Clinical evidence suggests rapid antidepressant effects, reduction in PTSD symptoms, and treatment of addiction. Studied at University of Sao Paulo and Sant Pau Hospital in Barcelona. Legal in ceremonial contexts in several countries.
University of Sao Paulo, Sant Pau Hospital Barcelona, Beckley Foundation
DMT
N,N-Dimethyltryptamine
Endogenous molecule produced naturally in the human body (pineal gland, lungs, retina). Short-acting when smoked (15-30 minutes) but profoundly immersive. Small Pharma (now Cybin) conducted Phase 2a trials for treatment-resistant depression using DMT-assisted therapy. Participants described the experience as among the most meaningful of their lives.
Imperial College London, Cybin (formerly Small Pharma), University of Michigan
Ketamine
NMDA receptor antagonist
The only psychedelic-adjacent compound currently FDA-approved for depression (as esketamine/Spravato). Works within hours, not weeks like traditional antidepressants. Effective for treatment-resistant depression and acute suicidal ideation. Available at licensed ketamine clinics nationwide. Johnson & Johnson's Spravato is covered by many insurance plans.
FDA-approved (Spravato) · Yale, Mount Sinai, NIMH
MDMA
3,4-Methylenedioxymethamphetamine
MAPS/Lykos Therapeutics completed Phase 3 trials for PTSD-assisted therapy. 67% of participants no longer met PTSD diagnostic criteria after three sessions. Produces deep empathy, reduced fear response, and enhanced therapeutic alliance. FDA review ongoing with regulatory complexities around blinding and the therapeutic model itself.
MAPS/Lykos Therapeutics, Emory University, Phase 3 complete
Microdosing
Sub-perceptual doses of psilocybin or LSD
Taking 1/10th to 1/20th of a standard dose on a schedule (e.g., Fadiman protocol: one day on, two days off). Reported benefits include improved mood, focus, creativity, and reduced anxiety. Rigorous double-blind studies show mixed results vs. placebo, though subjective reports remain overwhelmingly positive. Research ongoing at Imperial College and Maastricht University.
Imperial College, Maastricht University, James Fadiman Protocol