Psilocybin in magic mushrooms can affect the brain for weeks, research shows

Researchers have discovered that the psychedelic compound in magic mushrooms not only gives people a day trip, but can also affect the brain for weeks.

Experts say the research helps explain why taking psilocybin — the active ingredient in the drug — can result in a distorted sense of space, time and self during a trip, and also sheds light on the mechanism by which it may help treat major depression.

Dr. Joshua Siegel, a co-author of the work at the Washington University School of Medicine in St. Louis, said the research could also benefit companies testing new psychedelics and similar, but non-hallucinogenic, drugs.

“It could help determine whether a new drug is hitting the right targets and determine what the optimal dosing is,” he said.

Writing in the journal NatureSiegel and a team of colleagues explain how they conducted a randomized, controlled trial with seven healthy participants who agreed to take psilocybin in the name of science.

“It was also a requirement that they had taken a psychedelic substance at some point in their life, in part because they were taking a high dose, equivalent to 5 grams of mushrooms, and they were in a big, loud, thumping, claustrophobic magnet (while) they were taking psilocybin,” Siegel said, adding that the team had to make sure the participants could tolerate the situation.

“So we wanted to make sure they could tolerate that.”

Participants were randomly assigned to receive either a 25 mg dose of psilocybin or a 40 mg dose of methylphenidate—the generic form of Ritalin—but were kept in the dark about which one they had received. One to two weeks later, participants were given the drug they had not initially received.

Participants underwent MRI scans before, during, between, and after each drug, with four of the participants returning after six to 12 months to receive another dose of psilocybin and scans. Participants averaged 18 MRI visits per person.

The results show that taking psilocybin—but not methylphenidate—was associated with a loss of synchrony in what’s known as the default mode network, an interconnected group of brain regions that’s active when the mind wanders and the brain isn’t working on a specific task. Crucially, Siegel says, this network is involved in creating a sense of self, and also shows links to the perception of space and time.

“The interpretation is that (that disruption) is the cause of this very unusual experience (when taking psilocybin),” Siegel said.

Although the participants’ brain scans largely returned to normal the day after they took psilocybin, Siegel noted a reduction in communication between the default mode network and the anterior hippocampus (a part of the brain crucial for memory and perception of space and time). This reduction persisted for three weeks after the dose.

Siegel said the finding could help explain reports of an increase in flexibility in how people view themselves and their relationships with their environment after taking psilocybin. This plasticity could support psychedelic interventions for conditions such as treatment-resistant depression by making the brain more open to therapy.

Siegel added that while the research process was demanding, there seemed to be plenty of volunteers for psychedelic studies. “We had no trouble finding participants,” he said.