Research finds “profound” but temporary impact of psilocybin on brain networks

30 Jul 2024 --- Psilocybin, the active compound in magic mushrooms, temporarily scrambles a critical network of brain areas involved in introspective thinking, such as daydreaming and remembering. Researchers note that their study provides a neurobiological explanation for the compound’s mind-bending effects and potentially lays the groundwork for developing psilocybin-based therapies for mental illnesses.

The authors developed a process to visualize the impact of psilocybin on individual participants’ functional brain networks — neural communication pathways between brain regions — and to link changes in these networks with participants’ subjective experiences.

“There’s a massive effect initially, and when it’s gone, a pinpoint effect remains,” says Dr. Nico Dosenbach, a professor of neurology and co-senior author of the study.

“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.”

Temporary changes
The team from Washington University School of Medicine in St. Louis, US, recruited seven healthy adults to take a high dose of psilocybin (25 mg) or methylphenidate (40 mg) — the generic form of Ritalin — under controlled conditions. The results are published in Nature.

Trained experts supported the participants throughout their experience, preparing them for what they would likely experience, providing guidance and support during the experiment and helping them process what had occurred afterward. Each participant underwent, on average, 18 functional MRI brain scans before, during and up to three weeks after the experiment.

The team found psilocybin caused profound and widespread temporary changes to the brain’s functional networks. The compound desynchronized the default mode network, an interconnected set of brain areas commonly active simultaneously when the brain is not actively working on something.

The researchers visualized psilocybin’s impact on individual participants’ functional brain networks, linked to their experiences.After this desynchronization, the network re-established itself when the acute effects of the drug wore off. However, minor differences from pre-psilocybin scans persisted for weeks.

“These days, we know a lot about the psychological effects and the molecular/cellular effects of psilocybin,” adds Dr. Joshua Siegel, a psychiatry instructor and the study’s first author. But we don’t know much about what happens at the level that connects the two — the level of functional brain networks.”

“The idea is that you’re taking this system that’s fundamental to the brain’s ability to think about the self in relation to the world and temporarily desynchronizing it,” explains Siegel. In the short term, this creates a psychedelic experience. The longer-term consequence is that it makes the brain more flexible and potentially more able to reach a healthier state.”

In participants taking methylphenidate, the default mode network remained stable. The researchers note that psilocybin caused “more than threefold greater change than methylphenidate.”

Psychedelic effects
During their experience, participants rated their feelings of transcendence, connectedness and awe, using a validated Mystical Experience Questionnaire. The researchers note that the magnitude of changes to the functional networks corresponded to the intensity of each participant’s subjective experience.

Meanwhile, psilocybin also thoroughly distorted brain networks to the extent that individuals could no longer be identified until the acute effects wore off. Typically, a person’s functional brain network is “as distinctive as a fingerprint,” note the authors.

“The brains of people on psilocybin look more similar to each other than their untripping selves,” adds co-senior author Dosenbach. “Their individuality is temporarily wiped out. At a neuroscientific level, this verifies what people say about losing their sense of self during a trip.”

The authors caution that consumers should not interpret their study as a reason to self-medicate with psilocybin. The US FDA has not approved the drug as a treatment for depression or any other condition, and the researchers underscore there are risks to taking it without the supervision of trained mental health experts.

The study provides a road map to help develop psilocybin-based therapies for mental illnesses.Earlier this year, research reported that US law enforcement seizures of psilocybin-containing magic mushrooms grew 369% in five years. While these figures do reflect actual use, they indicate the availability of illicit drugs.

Next research steps
Earlier studies determined that psilocybin is a more effective treatment for symptoms of depression than controls. However, the authors called for more real-world research.

According to the researchers, the study creates a road map for other scientists to evaluate psychoactive drugs’ effects on brain function, which could potentially accelerate drug development efforts for several psychiatric illnesses, such as depression and post-traumatic stress disorder.

“We were able to get very precise data on the effects of the drug in each individual,” highlights Ginger Nicol, MD, the study’s senior author and an associate professor of psychiatry with experience running clinical trials with controlled substances.

“This is a step toward precision clinical trials. In psychiatry, we often don’t know who should get a particular medicine and how much or how often. As a result, we end up prescribing one medicine after another, tinkering with the dosage until we find something that works. By using this approach in clinical trials, we can identify the factors that determine who benefits and who doesn’t, and make better use of the medicines we have.”

By Jolanda van Hal

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