The first publicly-funded randomised controlled trial in the UK has found that a single dose of psilocybin, the active compound found in 'magic mushrooms', produced significant improvements in depression compared to a placebo.
This is the first publicly funded (funded by the National Institute for Health and Care Research (NIHR)), randomised trial of its kind delivering the treatment within an NHS setting in England, and found very promising results.
The study, published in Nature Medicine and known as Psilocybin in Depression Resistant to Standard Treatments (PsiDeR) trial, recruited 60 participants with treatment resistant depression, depression that has not responded to at least two prior treatments.
Half received a 25mg dose of psilocybin; half received a true placebo, meaning no psilocybin at all, with psychological support given to both groups. Neither participants nor the research team were told which group they were in.
This trial was funded by the NIHR Clinician Scientist Programme and is part of a larger body of research funded, in part, by the NIHR Biomedical Research Centre: Maudsley.
- A single dose of psilocybin eased depression far more than placebo, with the effect holding at six weeks.
- Psilocybin was given in a controlled community research setting, probing whether the treatment can be delivered outside a hospital environment.
- Trial funded by NIHR and delivered by South London and Maudsley NHS Foundation Trust in partnership with King's College London.
Significant improvement with psilocybin
At three weeks, those who received psilocybin showed a significantly greater drop in depression scores than those on placebo, measured using the Montgomery-Åsberg Depression Rating Scale. That difference was sustained at six weeks.
43 per cent of the psilocybin group met the threshold for treatment response at three weeks, rising to 50 per cent by six weeks, compared with three per cent 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 per cent of the psilocybin group met this threshold at three weeks, compared with three per cent 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 consultant psychiatrist at South London and Maudsley NHS Foundation Trust, said: "Here, we show that a randomised trial design of psilocybin compared to a true placebo was feasible in participants who had often failed many different types of treatment."
"People who were randomised to receive a dose of 25mg of psilocybin were much more likely to improve than those who were randomised to placebo up to 6 weeks of follow up. As is often the case in clinical depression, individual responses were very variable and some of the difference seen between groups will be due to non-drug 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.
Professor James Rucker, Lead Investigator, 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 per cent 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 NIHR Clinical Research Facility; King's, then moved partway through the study to a community mental health research building in a residential area - the Centre 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 trail 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.
Participant on 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 wider-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 non-serious 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. Whilst confirmatory trials are needed to demonstrate both the cost, and clinical effectiveness, these medications could one day be available on the NHS.
Professor Ben Carter, Lead Clinical Trial Methodologist, King's Clinical Trials Unit
