A single psilocybin dose desynchronized the brain’s core network for weeks, a Nature study found

When people take psilocybin, the compound in so-called “magic mushrooms,” the shift in conscious experience is obvious. What has been harder to see is what happens inside the brain’s wiring, and how long any of it lasts. A 2024 study published in Nature offers one of the most detailed looks yet, and it complicates the simpler story now circulating on social media.

Using repeated, high-density brain scans, researchers at Washington University in St. Louis tracked seven healthy adults before, during, and for three weeks after a single 25-milligram dose of psilocybin. To separate the drug’s specific effects from the generic effects of simply feeling altered, they ran each person through the same scans after a dose of methylphenidate, the stimulant in Ritalin, as an active comparison.

What the scans showed

During the experience, psilocybin was associated with a dramatic desynchronization of brain activity. Normally, regions within a network fire in coordinated rhythms, and different networks stay partly anticorrelated, a structure that helps keep mental states organized. Psilocybin appeared to flatten those distinctions: correlations within networks dropped and the usual boundaries between networks blurred. The acute disruption was more than three times larger than anything the stimulant produced.

The effect was strongest in the default mode network, a set of regions tied to self-reflection, mind-wandering, and our sense of space, time, and self.

The part the headlines get wrong

Here is the nuance the viral version of this finding tends to drop: most of that dramatic desynchronization was temporary. Once the acute experience passed, large-scale network activity largely returned to its normal pattern within about a day.

What lingered was narrower and more specific. The researchers observed a persistent reduction in connectivity between the anterior hippocampus and the default mode network that was still measurable up to roughly three weeks later. The authors describe this as a possible mechanistic correlate of the lasting psychological effects some people report, a hypothesis to investigate rather than a demonstrated outcome.

Why researchers find this interesting

Several mental-health conditions, including depression, anxiety, and rumination, have been associated in other research with brain circuits that are overly rigid and self-reinforcing. The idea that a single session might briefly loosen that rigidity is part of why psychedelics are being studied so intensely. This work offers a candidate brain-level mechanism for how such loosening could happen. But it is essential to be precise about what was and was not shown.

The bottom line

Researchers are exploring how psilocybin reorganizes brain activity, and this Nature study suggests a single dose may briefly free the brain’s networks from their usual coordinated patterns, with one specific change persisting for weeks. It is a window into mechanism, not evidence of benefit. The work was done in a controlled research setting with medical supervision, and the authors are clear that much remains unknown.

Sources

• ¶Siegel, J. S., et al. “Psilocybin desynchronizes the human brain.” Nature 632, 131-138 (2024).
• ¶Full open-access text (PubMed Central).