More than half a century after the U.S. government deemed psychedelic drugs to be of “no medical use,” scientists have begun re-evaluating that dismissive assessment with the tools of modern science. Dozens of clinical trials of psychedelic-assisted therapies for depression, anxiety, post-traumatic stress disorder (PTSD) and other conditions are underway or planned. So far, the results largely verify what Indigenous peoples with cultural traditions of psychedelic use have long known: Psychedelics are best treated not as party drugs but as potent medicines that can provide unique healing benefits when used appropriately.
Even as evidence grows of the drugs’ medicinal uses, however, little is known about how they work, or how best to harness their power in a way that benefits the people who need it most. As national leaders in neuroscience and implementation science, WashU Medicine researchers are poised to help solve these puzzles and transform psychedelics into safe, effective and accessible therapies for some of the most challenging conditions.
“We desperately need new approaches to treating mental health disorders,” says Ginger Nicol, MD, an associate professor of psychiatry at WashU Medicine. “The therapies we have do some good, but not enough. For PTSD, for example, our best therapies help only about a third of patients, which is tragic because PTSD causes enormous suffering. It literally kills people.
“Psychedelic-assisted therapy is something people want. They are already self-medicating, which can be really dangerous,” Nicol adds. “Psychedelic drugs have enormous potential to help people whom we can’t currently help, but the only way to turn that potential into reality is to conduct scientific research.”
Over the summer, a study by Nicol and two other WashU Medicine neuroscientists went viral for its colorful depiction of the effects of a psychedelic drug on the brain. The New York Times ran a story on it with the headline “This Is Literally Your Brain on Drugs”; comedian Stephen Colbert cracked a joke about it on his TV show, The Late Show with Stephen Colbert. Published in Nature, the world’s leading scientific journal, and illustrated with brightly colored brain maps, the study showed that psilocybin disrupts typical patterns of brain activity, and that the degree of disruption correlates with the depth of the mystical experience felt by the participant. In short, it made psychedelic trips — famously difficult to put into words — visible to others through the magic of modern neuroimaging techniques.
The study could have been done only at WashU Medicine. It relied on a technique developed in 2017 by a group of WashU Medicine neuroscientists including Nico U. F. Dosenbach, MD ’08, PhD ’08, a professor of neurology and one of the co-senior authors on the 2024 study. Known as precision functional mapping, the technique uses data from hours of brain scans per person to construct personalized brain maps.
One way to think about the brain is as networks of areas that become active under the same conditions, such as while looking at an object or moving the body. One of the most important such networks is the default mode network, the set of areas made active when the brain is doing nothing in particular. The default mode network was discovered in 2001 by Marcus Raichle, MD, the Alan A. and Edith L. Wolff Distinguished Professor of Medicine at WashU Medicine and one of the world’s leading neuroimagers, when he noticed that a set of brain areas shut off in concert when a person began a task and then turned back on when the task was completed and the person’s mind was allowed to wander. Subsequent studies demonstrated the role of the default mode network in introspective thinking such as daydreaming and remembering. Using precision functional mapping, Dosenbach and colleagues showed that each person’s default mode network pattern is as unique and as stable as a fingerprint.
As part of the 2024 study, the researchers scanned the brains of seven healthy adults before, during and after taking high doses of psilocybin. They discovered that the drug temporarily obliterated the participants’ unique default mode network patterns.
“The brains of people on psilocybin look more similar to each other than to their ‘untripping’ selves,” Dosenbach says. “Their individuality is temporarily wiped out. This verifies, at a neuroscientific level, what people say about losing their sense of self during a trip.”
Dosenbach would know better than most what that means. Along with being one of the leaders of the study — with Nicol and Joshua Siegel, MD, PhD, then an instructor in psychiatry at WashU Medicine and now an assistant professor of psychiatry at New York University — Dosenbach was also a study participant. During his trip, he lost his sense of self, becoming by turns his son, his daughter, the universe and Raichle. “Some people take psilocybin and see God,” Dosenbach says. “I’m an atheist and a neuroimager, so I saw Marc Raichle.”