Safety and Efficacy of Microdosing Psilocybin over 8 Weeks for Major Depressive Disorder: A Randomized Clinical Trial
Research Square February 23, 2026 Rotem Petranker, Norman Farb, Omer A. Syed et al.
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.