Meta-analysis of six trials: standard-dose psilocybin reduced depression symptoms

The question

Does psilocybin-assisted therapy reduce symptoms of major depressive disorder, and how do the effects and side effects change over time?

What they did

Researchers pooled results from six randomized controlled trials of psilocybin for major depressive disorder. They analyzed standard-dose sessions (25 mg, or 20-30 mg per 70 kg of body weight) separately from low-dose sessions (10 mg, or 15.05 mg per 70 kg). Comparison groups received placebo, niacin, a 1 mg dose of psilocybin, or were put on a waiting list. The abstract does not report the total number of people included.

What they found

Standard-dose psilocybin reduced depression scores more than the control conditions (standardized mean difference -1.05; 95% confidence interval -1.60 to -0.50), though results varied a lot between trials. When waiting-list studies were removed, leaving two double-blind trials that used a structured therapy protocol, the effect was smaller but still present (-0.70; -1.03 to -0.36). People given standard-dose psilocybin were more likely to respond (risk ratio 2.34) and to reach remission at 2-3 weeks (3.38), with response still higher at 6-12 weeks (2.61). They were also less likely to drop out (0.39), but more likely to report headache (2.06) and nausea (10.20) in the first 1-9 days; these resolved afterward. Low-dose psilocybin was no better than control.

The fine print

Only six trials were pooled, and the abstract does not state how many people took part in total. Some included studies used waiting-list controls, which cannot be blinded and tend to inflate apparent benefit. Differences between trials were substantial in the main analysis, and follow-up extended only to about 12 weeks. This summary is based on the abstract alone.

What it means

Pooled trial evidence suggests standard-dose psilocybin given alongside therapy can lower depression symptoms for at least several weeks, with short-lived nausea and headache, but the trials are few and differ from one another.

Evidence grade: Moderate. A meta-analysis of randomized trials, but based on only six small studies with high variability between them and differing control conditions.

This summary is based on the study’s published abstract.