MRIs pinpoint how magic mushrooms affect brain connectivity, paving way for effective mental health therapeutics

New imaging data could pave the way for more targeted and effective psilocybin-based therapies. 

The work, which was published this week in Nature, builds on what experts already know about the active compound in so called “magic mushrooms.” Experts have long indicated a role for psilocybin in treating various mental health conditions, as it can temporarily remove individuals from what might be a painful reality. However, it has never been clear exactly what neural mechanisms occur that cause people to feel like they are having an out of body experience. 

Now, experts from the Washington University School of Medicine in St. Louis are suggesting that psilocybin temporarily alters the signals of the brain’s default mode network—an area known to be associated with introspective thinking, mindfulness, memory recall, daydreaming, perception and self-awareness. The default mode network is most active when someone’s mind is inattentive and wandering. 

“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 get a closer look at how psilocybin affects the brain on a functional level, researchers conducted a small, yet thorough imaging comparison of healthy individuals who were given either a high dose of psilocybin or methylphenidate, the generic form of Ritalin. The substances were given under controlled conditions, with trained experts remaining with participants throughout their treatment. 

Each participant underwent an average of 18 functional brain MRI scans before, during and after their treatment to determine the trajectory of how each substance altered brain connectivity and function.  

Those exams revealed that psilocybin “massively disrupted functional connectivity” in the cortex and subcortex, three times more so than methylphenidate. The team observed that these changes were driven by desynchronization across spatial scales, notably in regions included in the default mode network. The magnitude of these changes gradually decreased but lasted for weeks. 

A pathway to therapeutics

“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 you’re totally desynchronizing it temporarily,” Siegel said. “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 come into a healthier state.” 

“That’s exactly what you’d want to see for a potential medicine,” co-senior author Nico U. F. Dosenbach, MD, PhD, a professor of neurology, added. “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 team suggested that their findings provide valuable new insight into where to look to determine how effective a drug is on an individual level. They said this information can be used to more effectively guide treatment for mental health disorders and deliver the appropriate therapeutics to patients much quicker, without having to go through what is often a lengthy trial and error process of determining which medications are the best fit. 

To learn more about the research, click here

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In addition to her background in journalism, Hannah also has patient-facing experience in clinical settings, having spent more than 12 years working as a registered rad tech. She joined Innovate Healthcare in 2021 and has since put her unique expertise to use in her editorial role with Health Imaging.

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