Magic mushrooms compound found to ‘significantly reduce’ depression symptoms in major trial

Psilocybin has been found to have a positive impact on patients suffering from treatment-resistant depression
Psilocybin in magic mushrooms is being trialled as a possible treatment for depression
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Daniel Keane2 November 2022

The psychedelic compound found in magic mushrooms has been found to significantly reduce symptoms of depression, according to a major trial.

Researchers at 22 international sites, including King’s College London and Maudsley NHS Foundation Trust, found that a single 25mg dose of psilocybin helped to alleviate symptoms of treatment-resistant depression.

Researchers found that those who took a larger dose (25mg) of psilocybin reported a significant reduction in symptoms after three weeks compared with those who took the lowest dose (1mg).

There are approximately 100 million people with treatment-resistant depression worldwide, which means that their symptoms do not respond to at least two antidepressant treatments. Depression affects about three in 100 people in England.

The phase 2b clinical trial was conducted at 22 sites in 10 countries in Europe and North America between March 2019 and September 2021. It is by far the largest trial of its kind.

For the study, 233 participants with treatment-resistant depression were allocated at random to receive a single 1mg, 10mg and 25mg dose of psilocybin. The doses were administered in specialised rooms designed to provide a calming atmosphere, and participants were supported by a therapist during the six to eight hours of the psychedelic experience.

All participants were assessed on the severity of their depressive symptoms the day before the psilocybin was administered, and follow up assessments were conducted on day two, and weeks one, three, six, nine and 12.

Neither the participants nor the researchers were aware which dose the participant had received.

Dr James Rucker, a consultant psychiatrist at King’s College London who was involved in the research, said the results were important as treatment options are often limited for those with treatment-resistant depression.

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

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

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

Professor Andrew McIntosh, head of the division of psychiatry at the University of Edinburgh, said the study’s results were the “strongest evidence so far to suggest that further, larger and longer randomised trials of psychedelics are justified”.

He added: “Psilocybin may (one day) provide a potential alternative to antidepressants that have been prescribed for decades.”

Professor David Nutt, head of the Centre for Neuropsychopharmacology at University College London and a former adviser to the Government on drug policy, said the results “support the theory that a psychedelic trip” could play a role in a patient’s therapeutic outcome. It also showed the “robustness of the psilocybin effect”, he added.

“Even though the trial was conducted in many centres in multiple countries, the effects were clinically significant, suggesting that the therapy is likely to be effective in a wider role out across the world.”

Earlier this year, the Standard reported how scientists were trialling the use of psilocybin in treating anorexia patients. The condition has the highest mortality rate of all psychiatric disorders because of medical complications and suicide, but there is no pharmacological treatment.

The depression trial was conducted by COMPASS Pathways in collaboration with the Psychoactive Trials Group at the Institute of Psychiatry, Psychology and Neuroscience and the South London and Maudsley NHS Foundation Trust.

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 three programme later this year, moving us closer to providing COMP360 psilocybin with psychological support for patients who desperately need it.”

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