In a small study of 24 adults with major depressive disorder, psilocybin-assisted therapy produced rapid and substantial antidepressant effects lasting up to one year, with no serious adverse effects. At 12 months, 75% of participants showed a treatment response (at least 50% reduction in depression scores) and 58% achieved remission. Participants' ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted increased well-being at 12 months but did not predict improvement in depression, suggesting that well-being changes may not be captured by standard depression scales. The authors note that long-term efficacy and safety are not yet known and larger studies are needed.
The FDA granted breakthrough therapy designation for phase 3 trials of MDMA as a treatment for PTSD. Phase 2 trials with 107 patients with chronic, treatment-resistant PTSD found that therapy alone led to 23% remission, therapy plus two MDMA sessions led to 55% remission, and a third MDMA session raised efficacy to 61%. At one-year follow-up, 68% of those who received MDMA-facilitated therapy no longer had a PTSD diagnosis. MDMA dampens the limbic system via the 5HT1A receptor, allowing patients to confront traumatic memories without being overwhelmed by fear, unlike classical psychedelics that work through the 5HT2A receptor system.