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Psilocybin can treat depression by restructuring the brain

A new study led by the University of California, San Francisco (UCSF) and Imperial College London (ICL) has found that psilocybin – the active compound found in magic mushrooms – fosters greater connectivity between different regions of the brains in depressed individuals. This frees individuals from ingrained patterns of self-focus and excessive rumination, and thus significantly alleviates their symptoms of depression.

The study comprised of nearly 60 people who had participated in two psilocybin trials. In the first one, all of the participants had treatment-resistant depression and knew that they were given psilocybin. In the second one, the participants were depressed, but not as severely as those in the first cohort, and they were not told whether they were given psilocybin or an antidepressant called escitalopram.

The researchers performed fMRI scans of the participants’ brains, and noticed that the psilocybin treatment helped reduce connections within brain areas which are tightly connected in depression, and increase connections to other regions of the brain that are not well integrated in patients with chronic depression. Participants on psilocybin have also shown improved cognitive functioning and appeared to be less emotionally avoidant as before. These changes lasted at least until the end of the observation period, almost three weeks after a second psilocybin dose. No such changes were found in the brains of those who took escitalopram, suggesting that psilocybin acts differently on the brain than common antidepressants. 

Psilocybin and other serotonergic psychedelics such as ayahuasca affect 5-HT2A receptors, which are numerous in brain areas that become overactive in depression. According to the scientists, psychedelic drugs may briefly disrupt these connections, and help rewire the brain in new ways in the days and weeks after treatment.

“In previous studies we had seen a similar effect in the brain when people were scanned whilst on a psychedelic, but here we’re seeing it weeks after treatment for depression, which suggests a carry-over of the acute drug action,” said study senior author Robin Carhart-Harris, the director of the Neuroscape Psychedelics Division at UCSF.

“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.”

While these findings are generally encouraging, scientists claim that patients with depression should not attempt to self-medicate with hallucinogenic mushrooms. The treatment should take place under controlled, clinical conditions, using fixed dosages, and involving appropriate psychological support before, during, and after taking the psychoactive drugs.

The study is published in the journal Nature Medicine.

By Andrei Ionescu, Staff Writer

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