A single dose of psilocybin reduces symptoms of depression

A multi-center clinical trial conducted by COMPASS Pathways at 22 international sites, including the’Institute of Psychiatry, Psychology & Neuroscience (IoPPN) from King's College London and the South London and Maudsley NHS Foundation Trust, has conducted the largest clinical trial to date on the effects of psilocybin on treatment-resistant depression.

The study is published in New England Journal of Medicine.

Study of the effects of psilocybin

The research team studied changes in depression severity, assessed using the Montgomery-Åsberg Depression Rating Scale, in participants with treatment-resistant depression for 12 weeks after a single dose of psilocybin and psychological support.

The Phase 2b clinical trial was conducted at 22 sites in ten countries in Europe and North America between March 2019 and September 2021. A total of 233 participants with treatment-resistant depression were randomized to receive a dose 25 mg, 10 mg or 1 mg psilocybin and psychological support. Those who received the 1 mg dose served as a control group. The trial was double-blind.

Dr James Rucker, Consultant Psychiatrist and Head of the Psychoactive Substances Trials Group at the IoPPN, in King's College London and South London and Maudsley NHS Foundation Trust, who took part in the research, said:

«While many patients with mental health problems improve with available treatments, a subset of patients do not improve, even though they try many different forms of treatment. This phenomenon is sometimes referred to as «treatment resistance». It can lead to a variety of other problems that have a serious impact on patients and those around them. Treatment options are often limited and accompanied by troublesome side effects and/or stigmatization. New treatment paradigms are therefore needed, and clinical research into new treatments is important. Psilocybin therapy could be a new treatment paradigm, but it needs to be tested in clinical trials. This is what we are doing at Psychoactive Trials Group, We are also developing new and pioneering treatments in collaboration with our colleagues at the Maudsley Centre for Advanced Treatments.»

«This study, which is by far the largest clinical trial on the use of psilocybin for depression treatment-resistant to date, showed that a single 25 mg dose of psilocybin improved participants» depressive symptoms compared with a 1 mg (control) dose. These results are a positive step in the right direction. Our task now is to study psilocybin for treatment-resistant depression in larger clinical trials with more participants, comparing it to both placebo and established treatments."

Treatment significantly reduced symptoms of depression

Participants were assessed for depression severity prior to psilocybin administration, and follow-up assessments were made on day two, and at weeks one, three, six, nine and twelve.

They received COMP360 psilocybin, a proprietary formulation of stabilized, high-purity polymorphic crystalline psilocybin synthesized. in specialized rooms designed to provide a non-clinical, soothing atmosphere. The psychedelic effects lasted between six and eight hours, and an experienced therapist offered support. All therapists participated in a detailed training program designed for the trial.

The researchers found that participants who received the 25 mg dose of psilocybin, with psychological support, experienced a rapid and greater reduction in depression scores than those who received the 1 mg control dose.

During the 12-week study, adverse events were observed. These included headache, nausea, dizziness and fatigue, which occurred in 84 % of participants in the 25 mg dose group, 75 % in the 10 mg dose group and 72 % in the 1 mg dose group. Suicidal thoughts and self-harm were observed in all groups. Most cases occurred more than a week after the initial dose.