Safety and Efficacy of Psilocybin in the Management of Treatment-Resistant Depression: A Systematic Review
Research Square May 11, 2026 Chloë K Walters, Sarentha Chetty, Thankhoe A Rants’o et al.
Psilocybin-assisted therapy shows promise as a treatment for adults with treatment-resistant depression, with early trials reporting rapid antidepressant effects and a favorable tolerability profile. A systematic review of six trials found that psilocybin lowered depressive scores in participants, while common adverse events included anxiety, nausea, headache, fatigue, and suicidal ideation; no serious safety concerns or physiological toxicity were identified. However, the evidence remains preliminary due to small sample sizes, open-label designs, and varied psychotherapy protocols. Larger, more rigorous randomized trials are needed to confirm efficacy, optimize dosing, and standardize psychological support.