Across 10 clinical trials, psilocybin-assisted therapy produced a large overall effect on depression (Cohen's d = 1.15), with controlled randomized trials alone showing d = 0.96 — still large by clinical standards — and no increased risk of serious side effects on dosing days. In the strongest 12-month follow-up study, 75% of participants maintained a treatment response and 58% were in full remission a year after just two psilocybin sessions. Evidence quality is rated low to moderate due to small samples and difficulty blinding participants to whether they took a psychedelic, but the signal holds up even after conservative sensitivity analyses, putting psilocybin among the most promising alternatives for the 20–30% of depression patients who don't respond to standard antidepressants.