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Researchers Uncover How Psilocybin May Affect Depression

A.J. Herrington

By A.J. Herrington

April 13, 2022

a person uses tweezers to portion out psilocybin mushroom doses

A recent study has found that psilocybin improves the connections between different regions of the brain in depressed people. The psilocybin treatment seems to allow participants to interrupt patterns of excessive self-focus and introspection. The study reveals a possible mechanism by which psychedelic drugs such as psilocybin, the active compound in magic mushrooms, can treat depression and other

characterized by patterns of fixed thinking.

“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,” David Nutt, head of the Imperial Centre for Psychedelic Research, said in a statement. “This supports our initial predictions and confirms psilocybin could be a real alternative approach to depression treatments.”

The study was done by researchers at the University of California, San Francisco and Imperial College London. Researchers analyzed the fMRI brain scans from nearly 60 people who had participated in two psilocybin trials. The first study included people with treatment-resistant depression who knew they were being given psilocybin. In the second study, participants were not as severely depressed and knew that they were being given psilocybin, although not the dosage. Participants in the second study were also given either the SSRI antidepressant escitalopram or a placebo. All patients received psychotherapy. Researchers monitored participants’ symptoms of depression throughout the study.

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Depression and Cognitive Performance Improved with Psilocybin

The brain scans of the participants were performed before and after treatment. They showed that treatment with psilocybin reduced connections in areas of the brain that are tightly connected in depression, including the default mode, salience and executive networks. Psilocybin also increased connections in other areas of the brain that had not previously been well integrated.

Participants also exhibited signs of improved cognitive performance and were less emotionally avoidant. The improvement in symptoms of depression correlated with changes in the participants’ brains. The observed changes lasted until the study ended three weeks after the second dose of psilocybin.

“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 Robin Carhart-Harris, Ph.D., the senior author of the study and the director of the Neuroscape Psychedelics Division at UCSF.

Psilocybin and other serotonergic psychedelics such as ayahuasca affect 5-HT2A receptors, which are prevalent in areas of the brain that show increased activity in people with depression. The researchers hypothesize that psychedelic drugs temporarily disrupted these connections. This allowed the connections to reform in new ways over the following days and weeks of the study.

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Study Results Consistent with Previous Research

The study’s authors noted that at least six clinical trials conducted over the last 15 years have shown impressive improvements in symptoms of depression when patients are treated with psilocybin therapy. However, the therapeutic mechanism of psilocybin and other psychedelic drugs is not entirely understood. The authors of the study recommended further research into the potential of psychedelics to treat symptoms of severe depression.

The researchers added that while the study’s findings are encouraging, people with depression should not attempt to self-medicate with psilocybin. They noted that the research was conducted as part of carefully controlled trials with regulated doses of psilocybin formulated in a laboratory. Patients also received professional psychological support before, during and after treatment with psilocybin.

“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,” said Carhart-Harris, who is the Ralph Metzner Distinguished Professor of Neurology, Psychiatry, and Behavioral Sciences and a member of the UCSF Weill Institute for Neurosciences. “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.”

The study, “Increased global integration in the brain after psilocybin therapy for depression,” was

in the journal Nature Medicine.

A.J. Herrington

About The Author

A.J. Herrington

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