Psilocybin — the active ingredient in magic mushrooms — could be just as effective as current antidepressants, but only when given in high doses, scientists say.
Experts came to this conclusion after reviewing evidence collected from 15 medical trials involving some 3,000 patients.
Writing in the prestigious journal, the BMJ, they said their review of psychedelics, a class of drugs that alter a person’s perception of reality, found while they were better than a placebo most don’t work better than current antidepressants.
Psychedelics examined included MDMA (also known as ecstasy), LSD, psilocybin, and ayahuasca, two of which Prince Harry controversially endorsed taking last year much to the criticism of medics.
But only psilocybin, and even then only in high doses, was shown to be as effective as a currently approved selective serotonin reuptake inhibitors (SSRI) a type of antidepressant.
Psilocybin — the active ingredient in magic mushrooms — could be just as effective as current antidepressants, but only when given in high doses, scientists say (stock image)
The authors concluded while psychedelics in general appeared to have been over-hyped high dose psilocybin ‘appeared to have the potential to treat depressive symptoms’.
Numerous studies have previously touted psychedelics, which are generally class A controlled drugs in the UK, as a potential mental health treatment including for depression.
However, the Taiwanese and British experts behind the new analysis said these were often flawed.
They said many trials failed to compare the effect of psychedelics to currently available medications and had often combined using them with therapy which made it impossible to unpick how effective the drugs actually were alone.
In an attempt to address this, researchers limited their analysis to clinical trials involving psychedelics and an antidepressant called escitalopram.
To be eligible, trials had to be using either type of drug alone on patients with acute depressive symptoms or via a head-to-head trial.
At the end only high-dose psilocybin was found to have the same effect as escitalopram.
However, the researchers noted that the effects of high-dose psilocybin may have been ‘overestimated’ due to the particular structure of that clinical trial which compared the drug head-to-head with escitalopram.
Nevertheless, they concluded: ‘Serotonergic psychedelics, especially high dose psilocybin, appeared to have the potential to treat depressive symptoms.
‘Our analysis suggested that the mean difference of high dose psilocybin was similar to that of current antidepressant drugs, showing a small effect size.’
Additionally, they said none of the trials they examined found a higher rate of serious adverse reactions, such as death, hospital admission or suicide attempt.
They did note several limitations however, including that they only compared the drugs in terms of how effective they were at treating depression not in other aspects that are also important to medication usage, such as adverse side effects.
Another limitation was small number of trials examined though 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, aren’t only one type of these drugs available.
SSRIs are the most widely prescribed type of antidepressant in the UK due to their safety and the fact most people can take them, but several alternatives can be provided.
Some British experts have previously supported the idea of using psilocybin as potential treatment for depression but have also called for further research, particularity on longer term outcomes.
Speaking on a separate evidence review published earlier this year Dr Paul Keedwell, consultant psychiatrist and fellow of the Royal College of Psychiatrists said: ‘In general, the results are impressive, with rapid improvement in most, and large effect sizes.’
But he added: ‘There are some concerns about expectation effects, because the majority of patients knew when they were getting 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 the psychedelic effects unpleasant, and care must be taken to ensure a calm environment for the treatment. Psychological preparation and debriefing, before and after dosing, respectively, are crucial.’
Last year Australia became the first country to approve the use of psilocybin for depression.
However, some experts are concerned that the therapy is going too far too fast.
Swinburne University Professor Susan Rossell, who leads Australia’s biggest trial on the effects of psilocybin on depression, said at the time more research needed to be done.
‘These treatments are not well established at all for a sufficient level of broad-scale implementation,’ she said.
‘We’ve got no data on long-term outcomes at all, so that worries me a lot, which is one of the reasons why I’m doing my very large study.’
Psilocybin impacts the part of the brain called the hippocampus which is responsible for reflecting on thoughts and experiences and helps individuals define their sense of self.
This is similar to how antidepressants target the brain to interrupt the negative thoughts associated with depression.
However, while psilocybin has shown some promise in combating issues like anxiety and depression, some individuals can experience persistent and distressing visions.
These reactions, which can occur as frequently as in one in 10 people who take the drug, amount to ‘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 from the leaves of a shrub
He said he took the drugs in an attempt to help him heal the ‘grief’ and ‘trauma’ he felt after the death of his mother. Pictured, Harry with Princess Diana in 1987
Supporters of psychedelic therapy, however, argue that bad trips are rare, and even when they do occur they often provide challenging personal insights that fuel healthy psychological growth.
The use of psychedelics for use of mental health conditions in general is controversial.
Some experts are worried about a current lack of good-quality evidence on their effectiveness as well as potential long-term outcomes.
The push for psychedelics has also come under a cloud after horrific claims of sexual assault from some patients who underwent clinical trials with the drugs.
Experts have also previously warned apparent celebrity endorsements of the positives of psychedelics, like Prince Harry, could encourage others to try the substances, with potentially dangerous consequences.
The Duke of Sussex has said he wouldn’t recommended taking ayahuasca recreationally but did tout its positives.
‘Doing it with the right people if you are suffering from a huge amount of loss, grief or trauma, then these things have a way of working as a medicine,’ he said.
His comments at the time were criticised by medics as well as the families of those who had died by suicide or intoxication shortly after taking the drug.
One of those was Dr Max Pemberton, an NHS psychiatrist in London and columnist for The Daily Mail, who said the comments were ‘highly irresponsible and ‘promoting yet another quack therapy’.
‘Harry plainly has no understanding of the serious damage these substances can wreak on users – damage that I see on mental health hospital wards with upsetting frequency,’ he said.
Calls for psychedelics to be made available to patients in the UK have been made before.
In February 2022, David Nutt, a professor of neuropsychopharmacology at Imperial College London, co-authored a review of research, in the Journal of Psychopharmacology.
It claimed psychedelic drugs have an unwarrantedly bad reputation and argued ‘many — albeit not all — of the persistent negative perceptions of psychological risks are unsupported by the currently available scientific evidence’.
Professor Nutt was fired as chair of the independent Advisory Council on the Misuse of Drugs (ACMD) in 2009 by Labour Home Secretary Alan Johnson after producing a paper for the Home Office which claimed Class A drug ecstasy is safer than equestrian sports.
He also recommended that cannabis, ecstasy and LSD should be considered less harmful than alcohol and cigarettes.
