Magic mushrooms study finds ‘significant’ effect on depression

One dose of psilocybin, the active ingredient in the psychedelic class A drug “magic mushrooms”, has a sustained and significant effect in treating cases of depression that are unresponsive to other drugs, a study has found.

A peer-reviewed, mid-stage trial published in the New England Journal of Medicine on Wednesday found one 25mg dose of the drug, alongside psychotherapeutic support, “significant[ly]” reduced symptoms of depression in patients who did not respond to other medication.

Researchers said the study, led by UK-based pharmaceutical group Compass Pathways, was the largest to date on the use of psilocybin as a treatment for depression and that its findings paved the way for regulatory approval.

The use of psychedelics to treat mental health conditions has been widely debated. At present a very limited number are approved by global regulators for medical use.

But more companies have in recent years begun to explore different ways of treating mental health conditions with psychedelics. The study is a step towards their regulation for medical use.

Ketamine is sometimes prescribed “off-label” in cases of treatment-resistant depression, while esketamine, a related compound, is approved in the UK and US as a nasal spray.

Micro-dosing, or taking small quantities of psychedelics, has also been anecdotally reported as beneficial, although researchers say more research on its effects is needed.

James Rucker, senior lecturer at King’s College London and an author of the NEJM study, said the lack of effective treatments available to people with treatment-resistant depression could “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.”

The study was conducted across 22 international sites, including King’s College London and the South London and Maudsley NHS Foundation Trust, which specialises in mental health.

Some 233 participants with depression resistant to treatment took part in the study, receiving 1mg, 10mg, or 25mg of psilocybin. Those in the first group acted as a control group, and neither researchers nor patients knew what strength of dose the latter took.

Patients were tracked for 12 weeks, with their symptoms rated the day before administration and at intervals thereafter.

Co-author Nadav Liam Modlin said the research had found that the drug enabled “powerful emotional breakthroughs” for patients and helped them develop “a sense of connection to themselves”.

Some side effects of psilocybin, including headaches, nausea, dizziness, fatigue and suicidal ideation, were reported across all dose groups.

Researchers said only one patient had a “bad trip”, which was managed with sedatives. The psychedelic part of the experience lasted hours and occurred under supervision, after which patients were free to go about their business.

Guy Goodwin, Compass’ chief medical officer and a co-author of the study, said the company planned to start its own late-stage, or phase 3, trial this year.

He said the results of the research suggested psilocybin had “a true pharmacological effect, a finding that is critical for it to be recognised as a new treatment option in the future”.

The compound, dubbed COMP360, has breakthrough designation from UK and US regulators, which can help hasten the development and marketing of new drugs. Compass is also trialling it in cases of post-traumatic stress disorder and the eating disorder anorexia nervosa.