Single dose of psilocybin for depression shows promising results in UK's first publicly funded randomized trial
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The first randomized controlled trial in the U.K. has found that a single dose of psilocybin, the active compound found in "magic mushrooms," produced significant improvements in depression compared with a placebo. This is the first publicly funded randomized trial of its kind to deliver the treatment within an NHS setting in England, and it found promising results.
The study, published in Nature Medicine and known as the Psilocybin in Depression Resistant to Standard Treatments (PsiDeR) trial, recruited 60 participants with treatment-resistant depression, a depression that had not responded to at least two prior treatments.
Half received a 25 mg dose of psilocybin; half received a true placebo, meaning no psilocybin at all. Psychological support was given to both groups. Neither the participants nor the research team were told which group they were in.
Significant improvement with psilocybin
At three weeks, those who received psilocybin showed a significantly greater drop in depression scores than those who received the placebo, measured using the Montgomery-Åsberg Depression Rating Scale. That difference was sustained at six weeks.
Of the psilocybin group, 43% met the threshold for treatment response at three weeks, rising to 50% by six weeks, compared with 3% of the placebo group throughout.
Rates of remission, meaning depression symptoms fell low enough to no longer meet clinical criteria, showed a similar pattern: 40% of the psilocybin group met this threshold at three weeks, compared with 3% on placebo, and this was sustained at six weeks.
Professor James Rucker, the study's lead investigator at King's College London's Institute of Psychiatry, Psychology & Neuroscience and a consultant psychiatrist at South London and Maudsley NHS Foundation Trust, said, "Here, we show that a randomized trial of psilocybin compared with a true placebo was feasible in participants who had often failed many different types of treatment."
"People who were randomized to receive a dose of 25 mg of psilocybin were much more likely to improve than those who were randomized to placebo up to six weeks of follow-up. As is often the case in clinical depression, individual responses were very variable, and some of the differences seen between groups will be due to nondrug factors."
"Publicly funded clinical trials are an important part of the jigsaw of evidence needed for a new intervention to find its place in the real world. Meanwhile, the wider evidence base for psilocybin therapy is growing rapidly and looks increasingly promising. This trial makes a strong case for larger publicly funded trials of psilocybin therapy in community settings, which are often more convenient and less anxiety-provoking for patients than hospital settings," said Rucker, lead investigator at the Institute of Psychiatry, Psychology & Neuroscience.
In the study, this true placebo design was chosen on the funder's advice to establish a clear safety baseline. Most participants correctly guessed their allocation: all of the psilocybin group and 70% of the placebo group. The authors note that expectation, not pharmacology alone, likely accounts for some of the difference between the groups.
Delivery within a community NHS setting
Recruitment began at the NIHR Clinical Research Facility at King's, then moved partway through the study to a community mental health research building in a residential area—the Center for Mental Health Research and Innovation.
Catherine Bird, senior clinical trials manager at the Institute of Psychiatry, Psychology & Neuroscience, said, "The move showed us that psilocybin can be administered safely outside a hospital setting. A calm, supportive environment with trained staff in the community suits most patients very well, and we didn't notice any new safety concerns."
A participant on the trial described the experience: "It got very intense two or three times…one part that got very emotional for me I felt like I was in a ribcage of some sort and in that I saw my dad holding my sister and that image stays with me because those are two people I have lost. I felt like it was a way of them saying we are here and that was definitely a point of emotional release. I think afterwards I felt pretty tired and broken."
"It has taken me a while to reflect and I think it just helped me understand my depression more and just 'feel' my feelings—I think I am glad I did it. It was very difficult—very painful—but I think that was what I needed and it came at the right time," said a participant in the PsiDeR trial.
Reflecting a real-world population
The trial also set no upper limit on the degree of treatment resistance a participant could have, unlike most commercially funded psilocybin trials. The trial was designed to test psilocybin therapy in people with a wide range of mental health treatment histories. This may be more reflective of the "real-world" population of patients psilocybin therapy may be offered to if it is licensed and approved for funding.
Across both arms, 287 nonserious adverse events were recorded (123 in the placebo group, 164 in the psilocybin group). The large majority were mild and resolved by the end of the trial. Four serious adverse events occurred, three in the psilocybin group and one in the placebo group. None was judged related to psilocybin itself.
"These are exciting findings that replicate industry-funded studies showing the considerable potential of psychedelics as a class of medication. While confirmatory trials are needed to demonstrate both cost and clinical effectiveness, these medications could one day be available on the NHS," said Professor Ben Carter, lead clinical trial methodologist at King's Clinical Trials Unit.
Publication details
James J. Rucker et al, Psilocybin-assisted therapy for treatment-resistant major depressive disorder in a public healthcare setting: a randomized controlled trial, Nature Medicine (2026). DOI: 10.1038/s41591-026-04541-0
Journal information: Nature Medicine
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PsychiatryPsychology & Mental healthClinical pharmacology Provided by King's College London Who's behind this story?
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