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• Posted April 12, 2022

How the 'Magic Mushroom' Drug May Tweak the Brain to Ease Depression

Psilocybin - the active component in "magic mushrooms" - may help rewire the brains of people with depression.

Psychedelics including psilocybin have shown promise in treating many mental health disorders in recent years, and a new study is among the first to begin to unravel precisely how they work.

"The brain becomes more open and flexible after a magic mushroom trip, enabling brain regions to talk more freely to one another, and the majority of these changes correlate with improvements in depressive symptoms," said study author Robin Carhart-Harris, director of the Neuroscape psychedelics division at the University of California, San Francisco.

For the study, the researchers analyzed functional MRI brain scans from 59 people who took part in two psilocybin trials. The brain scans were taken before psilocybin therapy and either one day or three weeks after.

In one study, all participants had treatment-resistant depression and knew they were being given psilocybin. In the second study, participants had milder forms of depression and received psilocybin or a conventional antidepressant. All of the study participants also saw a therapist.

The studies found that psilocybin improved how the brain's subnetworks communicated with one another, and this dovetailed with self-reported improvements in depression symptoms. The effects lasted for at least three weeks, Carhart-Harris said.

Scans of people who received an antidepressant didn't show similar changes in brain connectivity, suggesting that psilocybin works differently from conventional depression medications, he said.

If these findings are replicated in larger studies, psilocybin could become a mainstream depression treatment in the next five years, Carhart-Harris suggested.

In 2023, Oregon will become the first state with a psychedelic therapy program. Drug companies and several nonprofits are also studying psychedelics, including psilocybin, with psychiatric conditions in the hopes of getting a treatment approved by the U.S. Food and Drug Administration.

"We are also seeing changes in policy at the city level where certain cities are decriminalizing possession of magic mushrooms and related drugs," Carhart-Harris said.

The tide is turning, agreed Dr. Charles Grob. He is a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles.

"These drugs that were once marginalized and considered taboo are now the subject of great interest and activity, and both private and government funding," said Grob, who has no ties to the new study.

"These are encouraging preliminary results that certainly need to be replicated in a larger number of patients, but psilocybin is looking fairly promising for depression at this point," he said.

Both Grob and Carhart-Harris agree that psilocybin therapy is not something to try at home.

"This type of treatment begins with talk therapy and building up trust and a therapeutic relationship that precedes the mushroom trip in a controlled setting," Carhart-Harris said.

During a psilocybin session, you may listen to relaxing music and close your eyes as a mental health professional guides you.

"People experience strong emotions and breakthroughs and really open up emotionally," Carhart-Harris said. "It's extremely cathartic."

Exactly how many sessions are needed to see benefits isn't known, but it is likely more than one trip.

"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," Carhart-Harris said. "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."

Now, Carhart-Harris and his colleagues are looking at ways to improve the psychedelic therapy experience and environment to make it safer and more effective.

The therapy is not without risks, according to Grob.

"There is a downside and that becomes amplified when optimal set and setting are not established," he warned. "If a vulnerable individual takes these compounds under less than optimal conditions, all bets are off."

Manoj Doss, a postdoctoral research fellow at the John Hopkins Center for Psychedelic and Consciousness Research in Baltimore, offered a similar view.

"It can induce psychosis in some people, and we must be very cautious about what kinds of people should be taking these drugs," said Doss, who was not involved in the new study.

Doss and his colleagues recently published a study that highlighted some of the ways psilocybin affects the brain.

"Psychedelics and psilocybin may be another treatment in the armamentarium for depression, but it may not be that much better than available therapies, and it may only be effective in certain people," he said. "We are still in the early days."

The new study was published April 11 in the journal Nature Medicine.

More information

The U.S. National Institute on Drug Abuse has more on psilocybin and other psychedelic drugs.

SOURCES: Robin Carhart-Harris, PhD, director, Neuroscape psychedelics division, University of California, San Francisco; Charles Grob, MD, professor, psychiatry and behavioral sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles; Manoj Doss, PhD, postdoctoral research fellow, Johns Hopkins Center for Psychedelic and Consciousness Research, Baltimore; Nature Medicine, April 11, 2022