Psilocybin Therapy Changes Brain Wiring in Depressed People, Study Finds

New research continues to find evidence that psilocybin—the active ingredient in psychedelic mushrooms—can uniquely help people with depression. The study found that people undergoing psilocybin-assisted therapy experienced noticeable changes in brain patterns associated with depression, including when compared to a control group. People also reported a reduction in their depression symptoms alongside these brain changes.

Some researchers have been studying the potential mental health benefits of psychedelic substances like psilocybin since the 1970s. But it’s only in recent years that health authorities and governments have been more permissive of this research, following decades of harsh regulations.

Large-scale research into this field is still fairly new, but health regulators have signaled their willingness to consider these and similar drugs for formal approval. In 2019, a nasal spray formulation of the sometimes club drug ketamine was approved by the Food and Drug Administration. That same year, the FDA granted a breakthrough therapy designation to a non-profit company attempting to develop psilocybin as a depression treatment, which is meant to speed up the review process. States and cities have also begun to decriminalize psilocybin in general or for medicinal purposes.

Animal and clinical trial results of psilocybin-assisted therapy have been promising for depression and other conditions, including alcohol use disorder. But there’s still much we don’t understand about how these kinds of drugs are helping people with these ailments. This new research, published Monday in Nature Medicine, looks to add some insight.

The findings come from two previously conducted small-scale trials of psilocybin. In one, patients with treatment-resistant depression were given the treatment with full knowledge; in the other, patients with less severe depression were randomized to receive psilocybin or an active placebo (a SSRI antidepressant). All of these patients had their brains scanned before and after treatment, which included psychotherapy sessions.

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There are regions of the brain that appear to be overly connected and rigid in people who have depression, including those associated with cognition and attention. In this current study, the researchers found, people on psilocybin experienced a reduction in brain connectivity along those same regions, while those on the SSRI did not. The subjects also seemed to show an increase in connectivity between brain areas that aren’t as well-connected as they are in people who aren’t depressed. The net result of these shifts was that patients’ brains became better organized after taking psilocybin, the authors say.

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Importantly, these brain changes were also associated with an improvement in symptoms, meaning that people whose brain scans showed these changes to a greater degree also tended to feel more relief of their depression. And the changes seemed to last at least until three weeks past the second dose, when the study ended.

“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 senior study author Robin Carhart-Harris, director of the Neuroscape Psychedelics Division at the University of California, in a statement.

The findings appear to reaffirm that psychedelics like psilocybin can provide an alternative to conventional depression treatments, which sadly don’t work for many sufferers (as many as one-third of patients may be treatment-resistant). But the authors note that more research has to be done on how long these changes—and their associated benefits—can usually last in people, since some people do seem to experience a relapse of symptoms after a while. They also caution that these drugs shouldn’t be used without the supervision of mental health providers.