Psilocybin generates psychedelic experience by disrupting brain network

 Researchers report that psilocybin, the active ingredient in magic mushrooms, destabilizes a critical network of brain areas involved in introspective thinking. The findings provide a neurobiological exPeople who consume psilocybin-containing mushrooms -- otherwise known as magic mushrooms -- typically undergo a surreal experience in which their sense of space, time and self is distorted. Advocates have long argued that, under the right conditions, psychedelic experiences can alleviate mental distress, and a smattering of scientific studies suggests they may be right. Understanding precisely how the drug affects the brain will help scientists and doctors harness its therapeutic potential.

In a new study, researchers at Washington University School of Medicine in St. Louis report that psilocybin, the active compound in magic mushrooms, temporarily scrambles a critical network of brain areas involved in introspective thinking such as daydreaming and remembering. The findings provide a neurobiological explanation for the drug's mind-bending effects and lay some of the groundwork for the development of psilocybin-based therapies for mental illnesses such as depression and post-traumatic stress disorder.

planation for the drug's mind-bending effects."There's a massive effect initially, and when it's gone, a pinpoint effect remains," said co-senior author Nico U. F. Dosenbach, MD, PhD, a professor of neurology. "That's exactly what you'd want to see for a potential medicine. You wouldn't want people's brain networks to be obliterated for days, but you also wouldn't want everything to snap back to the way it was immediately. You want an effect that lasts long enough to make a difference."

The study, available July 17 in Nature, creates a road map other scientists can follow to evaluate the effects of psychoactive drugs on brain function, potentially accelerating drug development efforts for any number of psychiatric illnesses.

Psilocybin showed promise as a treatment for depression in the 1950s and '60s, but restrictive federal drug policy in subsequent decades quashed nearly all further research. In recent years, though, regulations have loosened, and interest in the field has been revived.

"These days, we know a lot about the psychological effects and the molecular/cellular effects of psilocybin," said first author Joshua S. Siegel, MD, PhD, an instructor in psychiatry. "But we don't know much about what happens at the level that connects the two -- the level of functional brain networks."

To fill that gap, Siegel pulled together a team including Dosenbach, who is an expert in brain imaging, and co-senior author Ginger E. Nicol, MD, an associate professor of psychiatry who has experience running clinical trials with controlled substances. Together, they devised a way to visualize the impact of psilocybin on individual participants' functional brain networks -- neural communication pathways that connect different brain regions -- and to correlate changes in these networks with subjective experiences.

The team recruited seven healthy adults to take a high dose of psilocybin or methylphenidate, the generic form of Ritalin, under controlled conditions. Because psychedelic trips carry the risk of users having negative or scary experiences, a pair of trained experts stayed with each participant throughout the experience. The experts helped prepare the participants for what they were likely to experience, provided guidance and support during each experiment, and helped the volunteers process what had occurred afterward. Each participant underwent an average of 18 functional MRI brain scans in the days to weeks before, during and up to three weeks after their experiences with psilocybin. Four participants returned six months later to repeat the experiment.

sources-science daily