Psilocybin temporarily dissolves brain networks

Inside your skull, your brain hums along with its own unique pattern of activity, a neural fingerprint that’s yours and yours alone. A heavy dose of psilocybin temporarily wipes the prints clean.

The psychedelic drug psilocybin dramatically changes how collections of nerve cells work in the brain, eliminating normal communication between brain regions, a new brain scanning study published July 17 in Nature shows. These brain images, taken before, during and after a high dose of psilocybin, expand the understanding of the drug’s effects, which is being studied for its promise in treating mental health disorders such as depression.

The brain scanning protocol researchers used was intense. “We had a small number of people, just seven participants in the whole study, but an enormous amount of data on each one,” says Joshua Siegel, a neuroscientist and psychiatrist at Washington University School of Medicine in St. Louis. Each person underwent about 18 functional MRI brain scans, one roughly every other day, over the course of the study.

That repeated scanning gives “an unprecedented view on how brain connectivity evolves after a dose of psilocybin,” says Alex Kwan, a neuroscientist at Cornell University who wasn’t involved in the study.

In the first part of the experiment, Siegel and colleagues recorded each person’s baseline brain activity, the unique patterns that emerge much like a fingerprint’s whorls, loops and arches when a person simply rests.

Later in the study, researchers gave participants 25 milligrams of psilocybin, a key ingredient in some hallucinogenic mushrooms, and watched what happened in the scanner. On a different day, for comparison, each participant also got a dose of methylphenidate, the generic form of Ritalin, a stimulant that affects the brain.

The effects of psilocybin were obvious, and big. “Psilocybin had humongous acute effects on the human brain,” says Nico Dosenbach, a neuroscientist also at Washington University School of Medicine. “Way, way, way bigger than the active control,” the methylphenidate.

Some of the biggest changes were in a brain system known as the default mode network, or DMN. This coordinated group of brain regions is active when nothing particular is happening. Scientists think that the DMN has a role in creating our sense of self (SN: 7/3/09). “It’s multiple parts of the brain across both hemispheres, but they’re all activating and deactivating in a very organized, synchronous way,” Siegel says. “And with psilocybin, it essentially becomes chaos.”

Dosenbach can attest that the drug causes a loss of sense of self. Along with being a researcher on the study, he was one of the seven study participants, giving him an unusual perspective on psilocybin’s effects on the brain. “You read about it, and you think about it and then you experience it, and you’re like, ‘Wow, that’s even more real.’”

Signs of those experiences showed up in the MRI scans. The team saw that psilocybin seemed to wipe clean the participants’ neural fingerprints. Dosenbach has an analogy to explain the brain changes in the scans: “You’d be like, ‘That is my face, and that is your face.’ And then you took a medicine, and we both had a puppy face — very similar, but very different from our normal faces.”

A day after taking the drug, most of psilocybin’s brain changes were gone, Siegel says. But one change persisted for three weeks. There was diminished coordination between the DMN and a part of the hippocampus, a structure involved in memory. Researchers don’t yet know how long this change might last, how it affects the brain overall or if it could hint at psilocybin’s therapeutic effects. It was not present in data from four of the participants who came in for scans six to 12 months later, but the study didn’t have enough data to say with certainty that it was gone.

The findings add to earlier work that sought to understand how psychedelic drugs change brains and show that the effects are far from simple. “Psilocybin is not simply tuning brain activity up or down,” Kwan says. “The results paint a more complex and nuanced picture for how psychedelics change neural activity dynamics than previously thought.”

Recent studies point to the promise of psychedelic drugs as therapies for depression, post-traumatic stress disorder, addiction and more (SN: 12/3/21). Understanding how these drugs affect the brain in the hours, days and months after taking it may lead to better treatments for some of these disorders.