Psilocybin-assisted therapy for treatment-resistant major depressive disorder in a public healthcare setting: a randomized controlled trial

Promising results from first UK trial of psilocybin for depression

A significant new UK study: a randomized, placebo-controlled feasibility RCT conducted within an NHS setting in England and published in Nature Medicine on 6 August 2026.

The key findings are:

1. A single 25 mg dose of psilocybin was associated with a large reduction in depressive symptoms.
At week 3, the adjusted between-group difference in MADRS was −10.41 points (95% CI −14.86 to −5.95; Cohen’s d = −1.70), favouring psilocybin. The difference was sustained at week 6 (−12.92 points, 95% CI −17.37 to −8.47).

2. Response and remission rates were substantially higher with psilocybin.
At week 3, 43% of participants in the psilocybin arm met the MADRS response criterion versus 3% with placebo; 40% versus 3% achieved MADRS remission. At week 6, the response rate increased to 50% in the psilocybin group.

3. Improvements extended beyond clinician-rated depression.
Compared with placebo, the psilocybin group showed improvements in self-reported depression, anxiety, overall health state, psychopathology and mental well-being across follow-up.

4. Psilocybin was generally well tolerated.
Adverse events were mostly mild and resolved, and the authors reported no substantial changes in clinical measures of suicidality or mania. The serious adverse events occurring in participants who received psilocybin were judged unrelated to treatment.

5. The NHS-delivery finding is particularly important.
Recruitment and retention were high: 60/60 participants attended the dosing visit and 59/60 completed MADRS assessments at every follow-up point. The study was also successfully delivered partly in a community mental-health setting, supporting the feasibility of conducting this type of intervention within UK public mental healthcare.

A highly promising NHS feasibility RCT showing a large and sustained antidepressant effect following a single 25 mg dose of psilocybin in people with treatment-resistant depression. The study also provides early evidence that psilocybin-assisted therapy can be delivered within an NHS/public mental-health setting, supporting the design of larger confirmatory trials. The authors state that the very large effect size should be interpreted cautiously because the placebo group showed little meaningful improvement and blinding was not maintained. They explicitly say expectancy effects likely account for some of the between-group difference

For psychedelic medicine in Britain, a particularly important aspect is the shift from evidence generated predominantly in specialist research settings toward evidence on how psilocybin-assisted therapy can actually be delivered within NHS mental healthcare. The authors note that the findings may help inform implementation if licensing is achieved and appropriate funding models are agreed.

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.

Rucker, J.J., Mantingh, T., Kerr-Gaffney, J. et al. Psilocybin-assisted therapy for treatment-resistant major depressive disorder in a public healthcare setting: a randomized controlled trial. Nat Med (2026). Read Paper

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