Psilocybin, the active compound in magic mushrooms, can ‘open up’ the brains of people with depression, helping patients to overcome rigid thought patterns and negative fixations, new research suggests.

A study led by the Imperial Centre for Psychedelic Research has shown that psilocybin therapy increases brain connectivity in people living with depression, even weeks after the treatment. The psychedelic acts in a way that conventional antidepressants do not, suggesting that psilocybin could be an effective, viable alternative to treating depression.   

“These findings are important because for the first time we find that psilocybin works differently from conventional antidepressants, making the brain more flexible and fluid, and less entrenched in the negative thinking patterns associated with depression,” says Professor David Nutt, head of the Imperial Centre for Psychedelic Research. 

The study, published in Nature Medicine, provides an indication of the underlying therapeutic mechanisms for psychedelic-assisted therapy which, according to Prof Nutt, “supports our initial predictions and confirms psilocybin could be a real alternative approach to depression treatments.”

Patients with depression will often display ruminative thought patterns, associated with rigid brain activity in a group of brain regions known as the default mode network. Excessive activity in this network has been shown to contribute to poor mental health but, as researchers of this study suggest, psychedelics could help the depressed brain to break out of this rut.  

The researchers analysed fMRI scans from two combined clinical trials of psilocybin therapy in 59 patients with major depressive disorder. In the first study, all patients received psilocybin treatment. In the second, patients either received psilocybin or the selective serotonin reuptake inhibitor (SSRI) escitalopram. All participants then received talking therapy with a trained psychedelic therapist. 

According to Imperial College London, the researchers “found an increase in communication between brain regions that are more segregated in depressed patients.” This increased brain flexibility was associated with self-reported improvements in depression symptoms. 

The effect seen with psilocybin is consistent across two studies, related to people getting better, and was not seen with a conventional antidepressant,” says Professor Robin Carhart-Harris, the study’s senior author. 

“We don’t yet know how long the changes in brain activity seen with psilocybin therapy last and we need to do more research to understand this. We do know that some people relapse, and it may be that after a while their brains revert to the rigid patterns of activity we see in depression.”

Psilocybin is one of numerous psychedelic substances being studied as a potential treatment for psychiatric disorders, including anxiety, anorexia, and addiction. “We have discovered a fundamental mechanism via which psychedelic therapy works,” Prof Carhart-Harris shares. The researchers now hope to investigate whether this same mechanism underpins these positive effects seen in other trials.

Since these findings come from controlled, clinical conditions using regulated doses of psilocybin, patients with mental health disorders are urged not to attempt self-medicating with psychedelics.

Psilocybin breaks rigid patterns in the depressed brain, study shows

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