Efficacy and Safety of Psilocybin in Treatment-Resistant Major Depression
JAMA Psychiatry March 18, 2026 Lea J. Mertens, Michael Koslowski, Felix Betzler et al. 9 citations
A phase 2b randomized clinical trial tested 25 mg of psilocybin with psychotherapy against a 5 mg dose and a placebo (nicotinamide) in 144 adults aged 25 to 65 with treatment-resistant depression who had stopped antidepressants. The primary outcome—a 50% or greater reduction in depression scores at six weeks—was not statistically significant: 17.0% of those receiving 25 mg responded, versus 12.5% on 5 mg and 10.6% on placebo. Exploratory analyses suggested a clinically meaningful reduction in depressive symptoms with the 25 mg dose. The treatment was generally well tolerated, but safety signals included higher reports of suicidal ideation on dosing days and two serious adverse reactions, one case of hallucinogen persisting perception disorder.