The largest clinical trial to date into the use of a psychoactive ingredient in magic mushrooms to treat treatment-resistant depression has produced promising results.

The trial, which involved researchers from Trinity College Dublin (TCD), suggests that the use of the ingredient psilocybin, along with psychological support, could be a beneficial therapeutic strategy for this form of depression.

Prompted by promising preliminary findings, a multi-centre, randomised, double-blind, phase 2b clinical trial was launched in 2018. Its aim was to determine the safety and potential antidepressant effects of a single dose of COMP360 psilocybin (25mg or 10mg) – a psychoactive ingredient in magic mushrooms - compared to 1mg, with psychological support in people with treatment-resistant depression.

The trial involved 233 people with treatment-resistant depression in 10 countries, including the Irish site at Tallaght University Hospital. It showed that patients who received a single dose of 25mg COMP360 psilocybin experienced a highly statistically and clinically significant rapid reduction in symptoms of depression compared to 1mg at three weeks.

Some 37% of people with treatment-resistant depression in the 25mg group met criteria for response at week three (≥50% decrease in depressive symptoms), while 29% met criteria for remission at week three.

Meanwhile, 20% of people in the 25mg group met criteria for sustained response at week 12.

Furthermore, COMP360 psilocybin was generally well-tolerated.

According to Dr John R. Kelly, a psychiatrist and clinical senior lecturer at TCD, this is the “largest and most rigorous clinical trial of psilocybin to date”.

“It shows a promising antidepressant signal for 25mg COMP360 psilocybin with psychological support and has paved the way for phase 3 clinical trials, which will determine whether it translates into a much-needed complementary treatment strategy in the psychiatry clinic.

“We look forward to the phase 3 trial and to the development of a translational psychedelic science research programme in Trinity College Institute of Neuroscience and Tallaght University Hospital. Ultimately, we hope that this will deliver tangible benefits to patients, the health service and to Irish society,” he commented.

The findings are published in the New England Journal of Medicine and can be viewed here.