Psilocybe cyanescens mushrooms, which contain the active compound psilocybin. Credit: Imperial College London / Thomas Angus
Psilocybin, the active compound in magic mushrooms, can be at least as effective as a leading antidepressant in a therapeutic setting.
This is the finding of a study conducted by researchers from the Center for Psychedelic Research at Imperial College London.
In the most rigorous trial to date to assess the therapeutic potential of a ‘psychedelic’ compound, researchers compared two sessions of psilocybin therapy to a six-week course of a leading antidepressant (a selective serotonin reuptake inhibitor called escitalopram). 59 people with moderate- to severe depression.
The results, published today (14 April 2021) in the New England Journal of Medicine, shows that while depression counts were reduced in both groups, the reduction occurred more rapidly in the psilocibin group and was greater.
However, the researchers warn that the main comparison between psilocybin and the antidepressant was not statistically significant. They add that larger trials with more patients over a longer period of time are needed to show whether psilocybine can perform as well as an established antidepressant.
For the psilocybin dosing sessions, volunteers received an oral dose of the drug in a clinical specialist setting while listening to a composite music playlist and being guided by their experiences through a psychological support team, which includes registered psychiatrists. All volunteers in the study received the same level of psychological support.
People treated with psilocybin – named ‘COMP360’ by the developers, COMPASS Pathways PLC – have shown clear improvements in a range of subjective measures, including their ability to feel pleasure and express emotions, greater decrease in anxiety and suicidal thoughts and increased feelings of well-being.
Dr Robin Carhart-Harris, head of the Center for Psychedelic Research at Imperial, who designed and led the study, said: “These results compare two doses of psilocybin therapy with 43 daily doses of one of the best SSRI antidepressants. perform, help contextualize psilocybin.Promise as a potential mental health treatment.Remission rates were twice as high in the psilocybin group as the escitalopram group.
‘One of the most important aspects of this work is that people can see the promise of psilocybine therapy properly delivered by seeing it compared to a more well-known, established treatment in the same study. Psilocybin performed very favorably in this head-to-head. ”
Growing evidence
During the study, 59 volunteers with moderate to severe depression received either a high dose of psilocybine and a placebo, or a very low dose of psilocybine and escitalopram.
In the psilocybin arm of the trial, 30 people received an initial dose of psilocybine (25 mg) at the beginning of the study, followed by a second dose (25 mg) three weeks later. They were given six weeks of daily placebo capsules to take: one per day after the first dosing session, and increased to two per day after the second dosing session.
In the escitalopram arm of the study, 29 people received 1 mg of psilocybin during the dosing sessions – a dose so low that it can be classified as inactive and probably ineffective. They also received escitalopram for six weeks: one 10 mg capsule per day after the first dosing session, which increases to two per day after the second dosing session (two mg per day) – the maximum dose for this SSRI.
All participants were assessed using standardized scales of severity of depressive symptoms. The most important measure, the QIDS-SR-16, was used to measure depressive symptoms on a continuous scale of 0-27, with higher scores indicating greater depression. At the start of the experiment, the mean score was 14.5 for the psilocibin group. But after six weeks, the scores decreased by an average of 8.0 points.
Response, defined as a baseline depression reduction of at least 50%, was seen in 70% of people in the psilocybin group, compared to 48% in the escitalopram group. In addition, remission of symptoms, measured as a score of 0-5 in week six, was seen in 57% of the psilocibin group, compared with only 28% in the escitalopram group.
Encouraging findings
The team emphasizes that although the findings are generally positive, the absence of a straightforward placebo group and the small number of participants limit conclusions about the effect of any treatment alone. They add that the experiment consists of largely white, majority male and relatively well-educated individuals, limiting extrapolations to more diverse populations.
The psilocibin group reported fewer cases of dry mouth, anxiety, drowsiness, and sexual dysfunction than the escitalopram group, and a similar number of adverse events in general. Headache experienced one day after dosing sessions was the most common side effect of psilocybin.
Dr Rosalind Watts, clinical director of the trial and formerly based at the Center for Psychedelic Research, said: “Context is crucial for these studies and all volunteers received therapy during and after their psilocybin sessions. Our team of therapists was ready for full provide support through sometimes difficult emotional experiences. ”
Professor David Nutt, lead researcher on the study and the Edmond J Safra chair in neuropsychopharmacology at Imperial, said: “These findings provide further support for the growing evidence base showing that psilocybine offers an alternative treatment to traditional antidepressants in people with depression.
“In our study, psilocybin worked faster than escitalopram and was well tolerated, with a very different profile. We are looking forward to further trials, which, if positive, could lead to psilocybin becoming a licensed drug. ”
To be careful
The authors warn that although the initial findings are encouraging, patients with depression should not attempt to do self-medication with psilocybin, as the team provided a special clinical and therapeutic context for the drug experience and a regulated dose in laboratory conditions. They emphasize that taking magic champions or psilocybin in the absence of these precautionary measures may not have a positive outcome.
Dr Carhart-Harris, added: ‘This latest finding is based on our previous research that tested psilocybine therapy for treatment-resistant depression, and provides the most compelling evidence to date to license the attempts at psilocybine therapy, as a to support regulated mental health intervention. I am deeply grateful for the philanthropic support that made this trial possible. ”
“I encourage both researchers and the public to immerse themselves thoroughly in our results, including the results available as a published appendix to the main report.”
Reference: April 14, 2021, New England Journal of Medicine.
DOI: 10.1056 / NEJMoa2032994
The study was funded by the Alexander Mosley Charitable Trust and the founders of the Center for Psychedelic Research. Infrastructure support was provided by the NIHR Imperial Biomedical Research Center and NIHR Imperial Clinical Research Facility.
* The QIDS-SR16 survey is a standardized survey with 16 questions used to record people on self-reported symptoms of depression.