Microdosing Psilocybin for Major Depressive Disorder: Study Protocol for a Phase II Double-Blind Placebo-Controlled Randomized Partial Crossover Trial
November 16, 2025 Zeina Beidas, Anya Ragnhildstveit, Adam Blackman et al. preprint
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.