Psilocybin, the active ingredient in magic mushrooms, could be as effective as current antidepressants, but only when administered in high doses, scientists say.
The experts came to this conclusion after reviewing evidence collected in 15 medical trials involving some 3,000 patients.
Writing in the prestigious magazine, the British Journal of MedicineThey said their review of psychedelics, a class of drugs that alter a person’s perception of reality, found that while they were better than a placebo, most worked no better than current antidepressants.
Psychedelics tested included MDMA (also known as ecstasy), LSD, psilocybin and ayahuasca, two of which Prince Harry controversially endorsed last year, to much criticism from doctors.
But only psilocybin, and only at high doses, has been shown to be as effective as selective serotonin reuptake inhibitors (SSRIs), a type of currently approved antidepressant.
Psilocybin, the active ingredient in magic mushrooms, could be as effective as current antidepressants, but only when given in high doses, scientists say (file image)
The authors concluded that while psychedelics in general appeared to have been overhyped, psilocybin in high doses “appeared to have the potential to treat depressive symptoms.”
Numerous studies have previously touted psychedelics, which are generally controlled class A drugs in the UK, as a possible treatment for mental health, including depression.
However, Taiwanese and British experts behind the new analysis said these were often flawed.
They said many trials failed to compare the effect of psychedelics with currently available drugs and often combined their use with therapy, making it impossible to determine how effective the drugs were on their own.
In an attempt to address this issue, the researchers limited their analysis to clinical trials that involved psychedelics and an antidepressant called escitalopram.
To be eligible, trials had to use either type of medication alone in patients with acute depressive symptoms or via a comparative trial.
In the end it was discovered that only psilocybin in high doses had the same effect as escitalopram.
However, the researchers noted that the effects of high-dose psilocybin may have been “overestimated” because of the particular structure of that clinical trial that compared the drug directly to escitalopram.
However, they concluded: ‘Serotonergic psychedelics, especially psilocybin at high doses, appeared to have the potential to treat depressive symptoms.
‘Our analysis suggested that the mean difference for high-dose psilocybin was similar to that for current antidepressants, showing a small effect size.’
Additionally, they said none of the trials they reviewed found a higher rate of serious adverse reactions, such as death, hospital admission or suicide attempt.
However, they noted several limitations, including that they only compared the drugs in terms of their effectiveness in treating depression, not on other aspects that are also important for drug use, such as adverse side effects.
Another limitation was the small number of trials examined, although the researchers said this was unavoidable given the limited number of eligible studies.
Another aspect to consider is that while the authors compared psychedelics to an antidepressant, escitalopram, this drug, and SSRIs in general, are not the only type of these drugs available.
SSRIs are the most commonly prescribed type of antidepressant in the UK due to their safety and the fact that most people can take them, but a number of alternatives may be offered.
Some British experts have previously supported the idea of using psilocybin as a possible treatment for depression, but have also called for more research, particularly into long-term outcomes.
Speaking about a separate evidence review published earlier this year, Dr Paul Keedwell, consultant psychiatrist and fellow of the Royal College of Psychiatrists, said: “Overall the results are impressive, with rapid improvement in the majority and large effect sizes.”
But he added: “There are some concerns about expectancy effects, because most patients knew when they were receiving the active condition or the higher dose of the same drug.”
Longer follow-ups would be welcome and there is more work to be done on optimal dosing.
‘The main disadvantage is that some patients find psychedelic effects unpleasant, and care should be taken to ensure that treatment is carried out in a calm environment. Psychological preparation and briefing, pre- and post-dose respectively, are essential.’
Last year, Australia became the first country to approve the use of psilocybin for depression.
But some experts are concerned that the therapy is moving too quickly.
Swinburne University professor Susan Rossell, who is leading Australia’s largest trial into the effects of psilocybin on depression, said at the time that more research was needed.
“These treatments are not well established enough to be implemented on a large scale,” he said.
“We don’t have any data on long-term outcomes, so that worries me a lot, and that’s one of the reasons I’m doing a large study.”
Psilocybin affects the part of the brain called the hippocampus, which is responsible for reflecting thoughts and experiences and helps people define their sense of self.
This is similar to how antidepressants attack the brain to disrupt negative thoughts associated with depression.
However, while psilocybin has shown promise in combating problems like anxiety and depression, some people may experience persistent, distressing visions.
These reactions, which can occur as frequently as one in ten people taking the drug, constitute “significant psychological distress” such as paranoia, Intense fear and even vivid hallucinations.
Last year, Prince Harry admitted to using psilocybin and ayahuasca, a plant-based psychedelic obtained from the leaves of a shrub.
He said he took the drugs in an attempt to help him heal from the “grief” and “trauma” he felt after his mother’s death. Pictured: Harry with Princess Diana in 1987
Proponents of psychedelic therapy, however, argue that bad trips are rare, and even when they occur, they often provide challenging personal perspectives that spur healthy psychological growth.
The use of psychedelics for the treatment of mental health disorders in general is controversial.
Some experts are concerned about the current lack of good quality evidence about its effectiveness as well as its possible long-term outcomes.
The push for psychedelics has also been overshadowed by horrific allegations of sexual assault by some patients who underwent clinical trials with the drugs.
Experts have also previously warned that apparent celebrity endorsements of the positive aspects of psychedelics, such as Prince Harry, could encourage others to try the substances, with potentially dangerous consequences.
The Duke of Sussex said he would not recommend taking ayahuasca for recreational purposes, but did highlight its positive aspects.
“If you’re going through a lot of loss, grief or trauma, if you’re dealing with the right people, these things can work like medicine,” he said.
His comments at the time were criticized by both doctors and the families of those who died by suicide or poisoning shortly after taking the drug.
One of them was Dr Max Pemberton, an NHS psychiatrist in London and a columnist for The Daily Mail, who said the comments were “highly irresponsible and promoting yet another quack therapy”.
“Harry clearly does not understand the serious harm these substances can cause to users, harm I see with alarming frequency on the wards of mental health hospitals,” he said.
Calls have already been made for psychedelics to be made available to patients in the UK.
In February 2022, David Nutt, professor of neuropsychopharmacology at Imperial College London, co-authored a research review, in the Journal of psychopharmacology.
He said psychedelic drugs have an unjustified bad reputation and argued that “many – though not all – of the persistent negative perceptions of psychological risks are not supported by currently available scientific evidence.”
Professor Nutt was sacked as chairman of the independent Advisory Council on the Misuse of Drugs (ACMD) in 2009 by Labour Home Secretary Alan Johnson after producing a document for the Home Office claiming that ecstasy, a class A drug, is safer than equestrian sports.
It also recommended that cannabis, ecstasy and LSD be considered less harmful than alcohol and cigarettes.
