A small study suggests a psychedelic compound in magic mushrooms is at least as effective as a commonly prescribed antidepressant.
Major depressive disorder affects around 10% of people in the UK. Drugs like Prozac are often the go-to treatment, but only 50% to 65% of patients see an improvement with existing medications, which often take several weeks to kick in.
Magic mushrooms' psychedelic compound psilocybin has previously shown promise for mood disorders and addiction.
To learn more, scientists from Imperial College London compared psilocybin against the antidepressant escitalopram – brand name Cipralex – in 59 people with a moderate-to-severe case of the mental health disorder.
Depression scores fell in both groups, with no significant difference between those on psilocybin or the antidepressant, possibly due to the study's small size.
The scientists noted, however, that depression symptoms reduced more quickly and at a "greater magnitude" among those on psilocybin.
While the news may sound positive, the team has stressed the results are not a green light to self-medicate with magic mushrooms, a class A illegal drug in the UK.
Thirty of the patients received two 25mg psilocybin pills – a "high dose" – called COMP360, three weeks apart.
They also took placebo capsules: one a day after the first psilocybin dosing session, rising to two per day after the second session.
The remaining 29 patients were given two 1mg psilocybin doses three weeks apart, alongside six weeks of daily escitalopram.
Escitalopram was given as a single 10mg daily capsule after the first session, rising to two per day after the second session, making the patients' daily intake 20mg – the maximum dose.
Like Prozac – drug name fluoxetine – escitalopram is a selective serotonin re-uptake inhibitor (SSRI); the most widely prescribed type of antidepressant in the UK.
SSRIs are thought to increase levels of the chemical messenger serotonin, which is linked to emotion and mood, in the brain.
Psilocybin at 1mg is considered to be an inactive dose that is "unlikely to have an effect", according to the Imperial scientists.
The compound works through a serotonin receptor that is "part of a pathway implicated in depression", they wrote in the New England Journal of Medicine.
All the patients received the same level of psychological support throughout the trial.
"Context is crucial for these studies, and all volunteers received therapy during and after their psilocybin sessions," said lead author Dr Rosalind Watts.
"Our team of therapists were on hand to offer full support through sometimes difficult emotional experiences."
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At the start of the study, those in the psilocybin group scored 14.5 out of 27 in a self-reported depression analysis, which fell by eight points after six weeks.
This is compared to a six-point drop among those on escitalopram, who started with an average score of 16.4.
While the two compounds are not statistically significantly different on this front, the results further show 70% in the psilocybin group saw their depression scores reduce by at least 50%, compared to just 48% of those on escitalopram.
More than half (57%) of those on psilocybin achieved remission of symptoms; defined as a depression score between zero and five at week six. This is compared to less than a third (28%) on escitalopram.
"These results comparing two doses of psilocybin therapy with 43 daily doses of one of the best performing SSRI antidepressants help contextualise psilocybin's promise as a potential mental health treatment," said co-lead author Dr Robin Carhart-Harris.
"Remission rates were twice as high in the psilocybin group than the escitalopram group.
"One of the most important aspects of this work is people can clearly see the promise of properly delivered psilocybin therapy by viewing it compared with a more familiar, established treatment in the same study.
"Psilocybin performed very favourably in this head-to-head."
Psilocybin was also found to be well-tolerated, with fewer cases of dry mouth, anxiety, drowsiness and sexual dysfunction than the escitalopram group, the results show.
Overall, however, the side effects were similar between the two groups.
"These latest findings build on our previous research testing psilocybin therapy for treatment resistant depression, and offer the most compelling evidence yet to support efforts towards licensing psilocybin therapy as a regulated mental health intervention," added Dr Carhart-Harris.
Experts not involved in the research have mixed feelings towards the results, with most agreeing further research is required.
"Re-medicalising psilocybin and related drugs is the most interesting project in contemporary psychiatry," said Professor Guy Goodwin, from the University of Oxford.
"The present study is not a quantum leap. It is under-powered and does not prove psilocybin is a better treatment than standard treatment with escitalopram for major depression; however, it offers tantalising clues it may be."
A lack of serious side effects has left some optimistic, particularly after previous research was halted over safety concerns.
"It does seem with careful administration and monitoring these treatments can be given safely," said Professor Anthony Cleare, from King's College London
He added, however, "psychedelic treatments are not a panacea and will not replace existing treatments for depression".
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Some noted how the participants largely "self-referred" themselves to the trial.
"News about trials like this often spreads organically, meaning those with pre-existing interests in psilocybin as a treatment are more likely to know about it, and volunteer, than those who are agnostic or against the treatment," said Dr James Rucker, from King's College London.
Those on 25mg psilocybin would also likely become aware of it, based on the compound's psychedelic effect.
Blinded trials, where neither the participants nor the investigators know who is taking what, are considered the gold standard of research.
The Imperial scientists also noted the study's participants were largely male, despite depression being more common among women.
Most were also white and "relatively well educated", meaning the results may not apply to the general population.
Dr Rucker also criticised the lack of a placebo arm in the trial, another gold-standard approach.
Professor David Owens from the University of Edinburgh agreed, adding: "One might say this is an 'interested' population, willing to go for novel approaches.
"With no placebo group, the extent of the placebo response cannot be assessed," he added.
Dr Sameer Jauhar from King's College London argued, however: "We know antidepressants outperform placebo and therefore the design is sound [when] testing psilocybin versus an active comparator."
Watch: The history of magic mushrooms