See How the Brain Responds to Psychedelic ‘Magic Mushrooms’

The psychedelic drug psilocybin—the active agent in so-called magic mushrooms—causes profound, temporary changes in a network of brain areas involved in introspective thinking, according to a new study published last week in Nature that imaged the brains of people given the drug.

The findings could provide insight into the potential therapeutic effects of psychedelics, a field that’s been gaining notoriety in recent years.

“Psilocybin, in contrast to any other drug we’ve tested, has this massive effect on the whole brain that was pretty unexpected,” Nico Dosenbach, a co-author of the study and neurologist at Washington University, tells the New York Times’ Andrew Jacobs. “It was quite shocking when we saw the effect size.”

Prior studies have also found that psilocybin disrupts brain networks, but the new research “provides a deeper resolution and insight into the nature of that disruption,” Brian Mathur, a neuroscientist at the University of Maryland who did not contribute to the findings, says to Nature News’ Max Kozlov.

Using psilocybin can create a disorienting effect, stimulate intense emotions and cause people to temporarily lose their sense of time and space. Researchers are looking into how psilocybin could be used to treat substance use disorders and other mental illnesses. A leading idea suggests the psychedelic compound can improve the brain’s ability to form new neural connections, known as neuroplasticity—which may encourage new perspectives or disrupt harmful patterns of thought.

In previous clinical trials, a single dose of psilocybin has led to rapid and sustained improvement in symptoms of depression, addiction and end-of-life anxiety. Research has also found the drug can change the brains of animals, such as mice and cats. But it’s unclear how the experiences induced by the drug are connected to changes in the human brain, the study authors write.

For the new research, scientists tracked changes in the brains of people who had taken psilocybin using functional magnetic resonance imaging (fMRI). Seven healthy adults received a total of around 18 scans each before, during and for three weeks after receiving a high dose of psilocybin. And, one to two weeks apart from the psilocybin dose, participants received a dose of methylphenidate, the generic form of Ritalin, which served as a control. The researchers also brought four participants back for another dose of psilocybin 6 to 12 months later.

Psilocybin's powerful short- and long-term effects on your brain are revealed by this intrepid precision imaging drug trial published in @Nature. As one of the scientists I was also a study volunteer. Spending hours in an MRI scanner, while tripping on 25 mg was the experience… https://t.co/H0PCxi7Q65 pic.twitter.com/kFL8sP1Nx0

— Nico Dosenbach (@ndosenbach) July 18, 2024

The psilocybin disrupted a set of brain areas called the default mode network that are active when the brain isn’t focused on a particular thing, according to a statement from Washington University. Scientists have found that these neurons may play a role in developing one’s sense of self. With psilocybin, neurons in that network started firing chaotically.

“I’ve never seen an effect this strong,” Shan Siddiqi, a psychiatric neuroscientist at the Harvard School of Medicine who was not involved in the research, says to Nature News.

“The activity in these networks became much more disorganized, and boundaries between the networks essentially evaporated,” Joshua Siegel, first author of the study and a neuroscientist at Washington University, tells the New York Times.

Compared to the control, psilocybin had a three times greater impact on the disorganization of this network.

Once the acute effects of the drug wore off, neurons in the default mode network settled down and resynchronized. But some small changes in the brain didn’t revert to normal for weeks, per the statement. As such, the study indicates psilocybin produces significant but temporary changes in the brain, especially in these areas involved with introspection.

Bertha Madras, a psychobiologist at Harvard Medical School who did not contribute to the findings, tells Medscape Medical News’ Patrice Wendling that the paper’s sample size is “excruciatingly small for trying to understand brain changes.”

“We had a small number of people, just seven participants in the whole study, but an enormous amount of data on each one,” Siegel says to Science News’ Laura Sanders.

Currently, psilocybin is not approved by the Food and Drug Administration as a treatment for any condition, the statement notes. Certain states, however, have legalized the drug for use in a supervised environment.

“The results paint a more complex and nuanced picture for how psychedelics change neural activity dynamics than previously thought,” Alex Kwan, a neuroscientist at Cornell University who wasn’t involved in the study, says to Science News.

Will Sullivan | | READ MORE

Will Sullivan is a science writer based in Washington, D.C. His work has appeared in Inside Science and NOVA Next.