Researchers got a closer look at exactly how psilocybin trips out the brain. In a new study, they found that the psychedelic drug can cause widespread alterations in brain activity, especially in the areas that govern our sense of self. The findings should give us more insight into how psilocybin and similar substances can be used to treat mental health disorders like depression.
The last few years have seen a dramatic surge of scientific interest in psilocybin and other psychedelic drugs, which have long been used recreationally. Anecdotally and in small studies, psilocybin used in combination with psychotherapy seems to help people struggling with depression, substance use problems, and post-traumatic stress disorder who haven’t responded to other options. Larger phase III trials of psilocybin for depression are now underway, with results expected to emerge as early as this year.
As exciting as this is, there remains a lot we don’t understand about how these drugs affect the brain. Study author and neuroimaging expert Joshua Seigel teamed up with his colleagues at Washington University in St. Louis to design a trial that could help answer some of these lingering questions.
A psilocybin brain
The randomized, controlled trial involved seven healthy adults, ages 18 to 45, who had their brains scanned via MRI before, during, and after taking a hefty dose of psilocybin (25 milligrams). The volunteers then returned six to 12 months later for a second dose. “One major advance in our study is that we tracked participants with regular scans for weeks after they took psilocybin,” Seigel told Gizmodo in an email.
![How Psilocybin Changes the Brain](https://gizmodo.com/app/uploads/2024/07/gif-2.gif)
The team spotted dramatic changes in brain activity right away. While these disruptions largely faded away within days, some changes could still be seen weeks later. “We saw that after a large dose of psilocybin, there was profound and widespread desynchronization to brain activity, altering connectivity across cortical networks and subcortical structures,” Seigel said.
The strongest change they observed was a lasting decrease in the connectivity between the anterior hippocampus and default mode network of the brain, a connection that’s thought to be vital to our sense of self-perception. These alterations seem to help explain a major aspect of a psychedelic trip: people who reported the most intense mystic experiences also had the largest changes in their default mode network.
The team’s findings, published Wednesday in Nature, are based on a small sample size, so it will take more work to confirm what they’ve seen. But the research does support the idea that these drugs can help treat depression. Some research has found that people with depression tend to have unusual patterns of brain activity in their default mode network, for instance. So by causing a little chaos, psilocybin might be shaking loose some of these harmful brain patterns.
Seigel also notes that completing a simple perceptual task seemed to dampen the effects of psilocybin in the brains of their volunteers. That finding might provide a neurobiological basis for “grounding”—a technique used in psychedelic-assisted therapy that asks people to focus on their physical reality during a session. Grounding is thought to help people manage their psychedelic trip safely and reduce the stress associated with intense thoughts or feelings.
Roadmap for the future
By measuring the brain changes associated with taking psilocybin, the researchers hope they’re creating a reliable roadmap that scientists can use when studying similar experimental drugs, including those trying to avoid the more mind-bending parts. Seigel is set to take a new position at New York University Langone Health’s Center for Psychedelic Medicine as an assistant professor, and one of his goals there will be to further sketch out this roadmap to help test some of these new drugs.
“There are dozens of companies testing out novel psychedelics and non-hallucinogenic psychedelic analogs,” he said. “The study provides a biomarker for testing drugs that are currently being developed that work similarly to psychedelics. It could help to determine if a novel drug is hitting the right targets and to decide what is the optimal dose.”