Psilocybin reduces depression symptoms, largest study to date suggests

Psilocybin – the active ingredient in magic mushrooms – could reduce symptoms in people with treatment-resistant depression, research suggests.

It is estimated that some 100 million people in the world suffer with the condition, which means they have not responded to at least two antidepressant treatments for their major depressive disorder.

The study of 233 people suggests that three weeks after people were given a single 25mg dose of psilocybin, they had lower levels of depressive symptoms than people treated with lower doses (1mg or 10mg).

The psilocybin in the study – called COMP360 – was not derived from magic mushrooms, but instead was created in a purely chemical process.

People were given the treatment in specialised rooms designed to provide a non-clinical and calming atmosphere.

Researchers say some reported a “dreamlike” state.

The psychedelic effects lasted between six to eight hours, and during this time an experienced therapist was in the room to provide psychological support.

All therapists underwent a detailed training programme designed for the trial.

After the psychedelic effects were fully dissipated participants were able to return home.

Dr James Rucker, consultant psychiatrist and lead for the Psychoactive Trials Group at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London and South London and Maudsley NHS Foundation Trust, took part in the research.

He said: “Whilst many patients with mental health problems get better with available treatments, a subgroup of patients do not even though they try many different forms of treatment.

“This is sometimes called ‘treatment resistance’. This can lead to a variety of other problems that seriously impact on patients and the people around them.

“Treatment options are often limited, coming with troublesome side effects and/or stigma.

“Therefore, new paradigms of treatment are needed, and clinical research of new treatments is important.

“Psilocybin therapy may be a new paradigm of treatment, but this needs to be tested in clinical trials.”

The study, published in the New England Journal of Medicine, investigated the change in the severity of depression in people with treatment-resistant depression over 12 weeks following a single dose of COMP360 psilocybin.

Researchers found that people reported a greater reduction in depression scores three weeks after taking a single 25mg dose of COMP360 psilocybin compared with those who took the lowest 1mg dose.

Some adverse effects, such as headaches, nausea, dizziness, fatigue, and thoughts around suicide, were reported across all dose groups.

Professor Guy Goodwin, chief medical officer at COMPASS Pathways, said: “We saw positive results in a particularly difficult to treat group of patients, and the highest dose of COMP360 psilocybin had the greatest impact on people’s depression.

“This suggests that COMP360 psilocybin has a true pharmacological effect, a finding that is critical for it to be recognised as a new treatment option in the future.

“We look forward to starting our phase 3 programme later this year, moving us closer to providing COMP360 psilocybin with psychological support for patients who desperately need it.”

According to the study, suicidal ideation and intentional self-injury were seen in all dose groups, as is common in treatment-resistant depression studies.

Most cases occurred more than a week after the COMP360 psilocybin session.

There was no mean worsening of suicidal ideation scores on the scale used in any dose group.

Suicidal behaviour was reported at least one month after COMP360 administration for three non-responders in the 25mg group.

The phase 2b clinical trial was conducted at 22 sites in 10 countries across Europe (Czech Republic, Denmark, Germany, Ireland, the Netherlands, Portugal, Spain, and the United Kingdom) and North America (Canada and the United States) between March 1 2019 and September 27 2021.

The trial, designed and funded by COMPASS Pathways, was conducted in collaboration with the Psychoactive Trials Group at the IoPPN and the South London and Maudsley NHS Foundation Trust.

Professor Andrew MacIntosh, head of the division of psychiatry at the University of Edinburgh, and member of the MQ Mental Health Research Science Council, said: “This new trial greatly improves our understanding of whether psilocybin could potentially help depressed people when conventional treatments have failed.”

He added: “It is the strongest evidence so far to suggest that further, larger and longer randomised trials of psychedelics are justified and that psilocybin may (one day) provide a potential alternative to antidepressants that have been prescribed for decades.”

Anthony Cleare, professor of psychopharmacology at King’s College London, said: “This is the largest study to date on the use of psilocybin for treatment-resistant depression.

“Given that patients had not responded to between two and four other treatments, it is a very encouraging finding that nearly four in 10 showed a clear response to a single dose of psilocybin.

“It is also notable how rapid in onset the treatment effects were, with the maximum effect seen the day after receiving the treatment.

“This contrasts with standard antidepressants, which take several weeks to reach maximum effect.”