Repeated low doses of psilocybin were safe and well tolerated in adults with major depressive disorder but did not show greater antidepressant effects than placebo. In a randomized, double-blind trial, 39 participants received either 2 mg psilocybin or placebo weekly for four weeks. Both groups reported similar reductions in depression scores on the PHQ-9 (psilocybin: -5.4; placebo: -6.0) and other measures. The microdose-first group showed slightly more improvement on a dysfunctional attitudes scale than the placebo-first group. No serious adverse events occurred, and symptom reductions continued during an open-label phase. Trial participation itself contributed to clinically meaningful improvement.
A phase II trial will test whether microdosing psilocybin (2 mg weekly) outperforms placebo for major depressive disorder. Forty adults will receive either psilocybin or placebo for four weeks, then all will receive psilocybin for another four weeks. Depression symptoms and other measures will be assessed at baseline, after four weeks, and after eight weeks, with follow-ups for two years. The study aims to clarify whether microdosing has genuine antidepressant effects or whether benefits are due to expectancy, and to inform future dose regimens and the therapeutic role of sub-threshold versus threshold doses.