A single dose of psilocybin – the psychedelic compound in magic mushrooms – can help reduce symptoms of depression.

The treatment has ‘significant impact’ when used alongside psychological support in patients who had not responded to other treatments, a large study has shown.

In patients with treatment-resistant severe depression who had the highest 25mg dose of COMP360 psilocybin, one in three were no longer found to be depressed at three weeks and one in five saw significant improvements at 12 weeks.

Reporting the results from the multi-centre trial in the New England Journal of Medicine, the researchers said the ‘significant impact’ seen in the phase 2 trial – the largest of psilocybin in depression so far – suggested larger and longer trials were now needed.

The study, done at centres across Europe and the US, compared 25mg, 10mg and 1mg doses (as a control) in 233 patients who were given the psilocybin in a nonclinical and calming room with an experienced therapist to provide psychological support, throughout the 6 to 8 hours that the psychedelic effects lasted.

But adverse effects, such as headaches, nausea, dizziness, fatigue, and thoughts around suicide, were reported across all dose groups.

Dr James Rucker, consultant psychiatrist and lead for the Psychoactive Trials Group at King’s College London who took part in the research said options were currently limited for those with treatment-resistant depression.

‘Psilocybin therapy may be a new paradigm of treatment, but this needs to be tested in clinical trials. These findings are a positive step in the right direction.

‘Our task now is to investigate psilocybin for treatment-resistant depression in larger clinical trials with more participants, comparing it both to placebo and to established treatments.’

Professor Guy Goodwin, chief medical officer at COMPASS Pathways, the company that led the trial said the findings suggest that ‘COMP360 psilocybin has a true pharmacological effect’ and a phase 3 study would be starting later this year.

Professor Anthony Cleare, Professor of Psychopharmacology at King’s College London, said the findings were very encouraging but several issues now need further study ‘before this can become part of regular clinical practice’.

‘The effects did start to wear off by three months, and we need to know how best to prevent the depression returning. This might involve adding in other treatments, such as psychological therapies, or repeating the psilocybin treatment periodically.

“There is also concern that because of the relatively small number of patients studied so far we don’t yet know enough about potential side effects, particularly whether some people may experience a worsening of some symptoms.’

Professor David Nutt, head of the Centre for Neuropsychopharmacology at Imperial College London, said the results solidified confidence in the general principle of use of psilocybin in this group.

‘Second it shows a dose-response relationship with doses of 10 and 1 mg [sub-psychedelic doses] showing less efficacy than the 25 mg dose which further supports the theory that a psychedelic trip itself plays a significant role in the therapeutic outcome.

‘Even though the trial was conducted in many centres in multiple countries the effects were clinically significant, suggesting that the therapy is likely to be effective in a wider role out across the world,’ he added.

A version of this story was originally published on our sister publication Pulse.