Patients unresponsive to conventional treatments benefit when treated with natural psychoactive compound, but researchers warn against self medication

Magic mushrooms may effectively “reset” the activity of key brain circuits known to play a role in depression, the latest study to highlight the therapeutic benefits of psychedelics suggests.

Psychedelics have shown promising results in the treatment of depression and addictions in a number of clinical trials over the last decade. Imperial College London researchers used psilocybin – the psychoactive compound that occurs naturally in magic mushrooms – to treat a small number of patients with depression, monitoring their brain function, before and after.

Images of patients’ brains revealed changes in brain activity that were associated with marked and lasting reductions in depressive symptoms and participants in the trial reported benefits lasting up to five weeks after treatment.

Dr Robin Carhart-Harris, head of psychedelic research at Imperial, who led the study, said: “We have shown for the first time clear changes in brain activity in depressed people treated with psilocybin after failing to respond to conventional treatments.

“Several of our patients described feeling ‘reset’ after the treatment and often used computer analogies. For example, one said he felt like his brain had been ‘defragged’ like a computer hard drive, and another said he felt ‘rebooted’.

“Psilocybin may be giving these individuals the temporary ‘kick start’ they need to break out of their depressive states and these imaging results do tentatively support a ‘reset’ analogy. Similar brain effects to these have been seen with electroconvulsive therapy.”

For the study, published in Scientific Reports on Friday, 20 patients with treatment-resistant depression were given two doses of psilocybin (10 mg and 25 mg), with the second dose a week after the first. Of these, 19 underwent initial brain imaging and then a second scan one day after the high dose treatment. The team used two main brain imaging methods to measure changes in blood flow and the crosstalk between brain regions, with patients reporting their depressive symptoms through completing clinical questionnaires.

Immediately following treatment with psilocybin, patients reported a decrease in depressive symptoms, such as improvements in mood and stress relief.



MRI imaging revealed reduced blood flow in areas of the brain, including the amygdala, a small, almond-shaped region of the brain known to be involved in processing emotional responses, stress and fear.

The authors believe the findings provide a new window into what happens in the brains of people after they have ‘come down’ from a psychedelic, with an initial disintegration of brain networks during the drug ‘trip’ followed by a re-integration afterwards.

Last year, two US studies showed that a single dose of psilocybin could lift the anxiety and depression experienced by people with advanced cancer for six months or even longer.



The Imperial College researchers acknowledge that the significance of their results is limited by the small sample size and the absence of a control/placebo group for comparison. They also stress that it would be dangerous for patients with depression to attempt to self-medicate.



Professor David Nutt, director of the neuropsychopharmacology unit in the division of brain sciences, and senior author of the paper, said: “Larger studies are needed to see if this positive effect can be reproduced in more patients. But these initial findings are exciting and provide another treatment avenue to explore.”

The authors currently plan to test psilocybin against a leading antidepressant in a trial set to start early next year.

The research was supported by the Medical Research Council, the Alex Mosley Charitable Trust and the Safra Foundation.

