Psilocybin-assisted therapy for treatment-resistant major depressive disorder in a public healthcare setting: a randomized controlled trial
In brief
Psilocybin lowered depression scores by about 10 points versus placebo
In a double-blind NHS trial, a single 25-mg psilocybin dose with psychological support reduced Montgomery-Åsberg scores by roughly 10 points at three weeks compared with placebo, and the benefit persisted to six weeks. Recruitment and retention were high, and adverse events were non-serious, supporting larger confirmatory studies.
- Journal
- Nature medicine (Q1)
- Published
- 6 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- James J Rucker, Tim Mantingh, Jess Kerr-Gaffney, Catherine Bird, Petrina Chu, Nadav Liam Modlin, et al.
- PMID
- 42562964
- DOI
- 10.1038/s41591-026-04541-0
Why clinicians should know about it
- Picked for Psychiatry and Mental Health (paper of the day, 8 August 2026): Psilocybin‑assisted therapy for treatment‑resistant depression
Abstract
Psilocybin-assisted therapy may be a promising new treatment for treatment-resistant depression. We examined the feasibility of administering a single 25-mg dose of psilocybin or placebo with psychological support in a randomized controlled trial design with 6 weeks of follow-up. A two-arm, double-blind, randomized, placebo-controlled feasibility trial was conducted at one National Health Service (NHS) site in England. Eligible participants met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for major depressive disorder and had an inadequate response to ≥2 antidepressant treatments or ≥1 antidepressant plus ≥1 psychotherapy. Participants received 25-mg psilocybin or placebo with preparation, dosing support and integration. Primary outcomes were recruitment, retention and estimation of the Montgomery-Åsberg Depression Rating Scale (MADRS) variance. A multilevel regression analysis with an intention-to-treat population was used. Sixty participants were randomized (1:1), balanced by age, sex and prior psilocybin exposure, and 59 of 60 participants completed the MADRS at all follow-up visits. The adjusted between-group difference at week 3 on the MADRS was -10.41 (95% confidence interval: -14.86 to -5.95; Cohen's d = -1.70), favoring psilocybin, which was sustained at week 6. In total, 123 and 164 nonserious adverse events occurred in the placebo and psilocybin arms, respectively. Findings support a future confirmatory trial. EudraCT no.: 2018-003573-97 .
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.