Your brain on shrooms — how psilocybin resets neural networks

Taking psilocybin, the hallucinogenic compound found in magic mushrooms, temporarily resets entire networks of neurons in the brain that are responsible for controlling a person’s sense of time and self, finds a study that repeatedly imaged the brains of seven volunteers before, during and after they took a massive dose of the drug.

The findings, published in Nature on 17 July¹, could offer insights into why the compound might have a therapeutic effect on some neurological conditions.

Researchers “saw such massive changes induced by psilocybin” that some study participants’ brain-network patterns resembled those of a different person entirely, says Shan Siddiqi, a psychiatric neuroscientist at Harvard School of Medicine in Boston, Massachusetts. “I’ve never seen an effect this strong.”

Most of these changes lasted for a few hours, but one key link between different parts of the brain remained disrupted for weeks.

Psychedelic medicine

Psilocybin is one of several psychedelic drugs, including LSD, ketamine and MDMA (also known as ecstasy), that are being investigated as therapies for conditions such as depression and post-traumatic stress disorder. Despite promising data that have sped treatments towards approval, researchers still don’t fully understand the mechanism that underlies their therapeutic effects.

Many studies have investigated how psychedelics affect individual cells, but Joshua Siegel, a systems neuroscientist at the Washington University School of Medicine in St. Louis, Missouri, took a broader approach to look at how psilocybin affects networks of neurons across the whole brain.

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Siegel and his colleagues tracked activity in the brains of seven healthy adults before, during and after they took a high dose of psilocybin. The researchers used functional magnetic resonance imaging (fMRI) to obtain images of blood-flow changes in different parts of the brain — a proxy used to measure how groups of neurons across the brain communicate with one another.

The researchers compared these fMRI scans with images of the same participants’ brains when they did not take any drug or when they took a stimulant. They found that psilocybin caused groups of neurons that normally fire together to become desynchronized. These effects were localized to a group of brain regions called the default mode network, which is usually active when the brain is at ‘wakeful rest’ — for example, during daydreaming — rather than focusing on a task. Although most of the neurons in this network seemed to get back in sync once the acute effects of the drug had worn off, the communication between the default mode network and a brain region called the anterior hippocampus — which is involved in creating our senses of space, time and self — was diminished for weeks.

The researchers also found that a mental exercise called ‘grounding’, which is commonly used in psychedelic therapy to dampen the unpleasant effects of a drug by diverting the recipient’s attention to their surroundings, diminished psilocybin’s effects on the brain. This suggests there could be a neurological signal that grounding techniques can influence, Siegel says.

Deeper insights

Although past experiments have also found that psilocybin disrupts brain networks^2,3, this study “provides a deeper resolution and insight into the nature of that disruption”, says Brian Mathur, a systems neuroscientist at the University of Maryland School of Medicine in Baltimore.

The approach was unusual: the researchers homed in on a smaller number of participants than are typically recruited for brain-imaging studies, instead opting to scan each participant about 18 times, creating a mountain of data that the authors could use to support their conclusions.

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Mathur cautions that these data cannot show what precisely causes the potential therapeutic benefit of psilocybin — but they offer tantalizing clues. “It’s possible psilocybin is directly causing” the brain-network changes, he says — or perhaps it is creating a psychedelic experience that in turn causes parts of the brain to behave differently, he says.

Siddiqi agrees, adding that it will be useful to untangle whether psilocybin’s blood-flow changes in the brain, which is measured by fMRI, or its direct effects on neurons — or both — are responsible for the brain-network disruptions. Siegel hopes to conduct further experiments to investigate the effects of psilocybin on the brains of people with conditions such as depression.

“The best part of this work is that it’s going to provide a means forward for the field to develop further hypotheses that can and should be tested,” Mathur says.