In a therapeutic environment, psilocybin, the main component in magic mushrooms, may be at least as effective as a leading antidepressant medicine.

This is the conclusion of a study conducted by experts at Imperial College London's Centre for Psychedelic Research.

Researchers compared two sessions of psilocybin therapy with a six-week course of a leading antidepressant (a selective serotonin uptake inhibitor called escitalopram) in 59 people with moderate-to-severe depression in the most rigorous trial to date assessing the therapeutic potential of a psychedelic compound.

The findings, which were published today in the New England Journal of Medicine, demonstrate that while depression levels were lowered in both groups, the psilocybin group had faster and larger decreases.

The researchers do warn, however, that the primary comparison between psilocybin and the antidepressant was not statistically significant. They go on to say that bigger studies with more patients over a longer length of time are needed to determine whether psilocybin works as well as, or better than, a known antidepressant.

Volunteers received an oral dosage of psilocybin in a professional clinical environment while listening to a tailored music mix and were guided through their experiences by a psychological support team that comprised licensed psychiatrists. The study's subjects all got the same amount of psychological care.

People who took psilocybin, dubbed 'COMP360' by its creators, COMPASS Pathways PLC, exhibited significant gains in a variety of subjective measures, including their capacity to feel pleasure and express emotions, lower levels of anxiety and suicide thoughts, and an enhanced sense of wellbeing.

"These results comparing two doses of psilocybin therapy with 43 daily doses of one of the best performing SSRI antidepressants help contextualize psilocybin's promise as a potential mental health treatment," said Dr. Robin Carhart-Harris, head of the Centre for Psychedelic Research at Imperial, who designed and led the study. The psilocybin group had twice as many remissions as the escitalopram group.

"One of the most important parts of our work is that people can plainly see the potential of properly provided psilocybin therapy by comparing it in the same trial to a more familiar, established treatment." In this head-to-head, psilocybin fared pretty well."

Increasing Evidence

59 participants with moderate-to-severe depression were randomly assigned to receive either a high dosage of psilocybin and a placebo or a very low combination of psilocybin plus escitalopram.

In the psilocybin arm of the experiment, 30 participants were given a 25mg dosage of psilocybin at the start of the research, followed by another 25mg dose three weeks later. They were given daily placebo pills to ingest for six weeks, one per day after the first dosage session and two per day following the second dosing session.

In the escitalopram arm of the trial, 29 subjects were given 1mg psilocybin during the dosing sessions – a dose so low that it was classified as non-active and unlikely to have an impact. They were also given daily escitalopram for six weeks, starting with one 10mg capsule per day after the first treatment session and gradually increasing to two per day after the second dosing session (20mg per day) — the maximum dose for this SSRI.

The severity of depression symptoms was measured using standardized measures for all subjects. The main measure, the QIDS-SR-16, was used to assess depressive symptoms on a scale of 0-27, with higher scores indicating more depression. 

The mean score for the psilocybin group at the start of the study was 14.5. However, after six weeks, scores dropped by an average of 8.0 points.

Response, defined as a 50% reduction in depression ratings from baseline, was found in 70% of persons in the psilocybin group vs 48% in the escitalopram group. Furthermore, 57 percent of the psilocybin group had symptom remission (defined as a score of 0-5 at week six), compared to just 28 percent of the escitalopram group.

Optimistic Findings

While the findings are generally good, the lack of a straight placebo group and the limited number of participants restrict inferences regarding the benefit of either medication alone, according to the team. They also point out that the trial sample was predominantly white, male, and reasonably well-educated, which restricts generalization to more diverse groups.

The psilocybin group had fewer incidences of dry mouth, anxiety, sleepiness, and sexual dysfunction than the escitalopram group, but had a similar total rate of side effects. The most prevalent negative effect of psilocybin was headaches one day following dosing sessions.

"Context is critical for this research, and all volunteers got treatment during and after their psilocybin sessions," said Dr. Rosalind Watts, clinical head of the experiment and formerly located at the Centre for Psychedelic Research. Our therapists were on hand to provide full support during some challenging emotional moments."

"These findings provide further support for the growing evidence base that shows that in people with depression, psilocybin offers an alternative treatment to traditional antidepressants," said Professor David Nutt, principal investigator on the study and the Edmond J Safra Chair in Neuropsychopharmacology at Imperial.

"Psilocybin functioned faster than escitalopram in our research and was well tolerated, with a significantly distinct side effect profile." We are looking forward to more studies, which, if successful, will lead to psilocybin being a regulated medication."

Caution Is Required

While the preliminary findings are encouraging, the authors caution that patients with depression should not attempt to self-medicate with psilocybin because the team provided a special clinical and therapeutic context for the drug experience as well as a regulated dose formulated in laboratory conditions. They emphasize that consuming magic mushrooms or psilocybin without these precautions may not result in a beneficial outcome.

"These current findings expand on our prior study evaluating psilocybin therapy for treatment-resistant depression, and give the most convincing evidence yet to support attempts to license psilocybin therapy as a regulated mental health intervention," Dr. Carhart-Harris stated. I'm grateful for the generous assistance that enabled this experiment to take place."

"I highly encourage both scholars and the general public to dive carefully into our findings, particularly those released as an appendix to the main study." if you want to get more information, please visit the website mungus.com