Washington University study in Nature shows psilocybin desynchronizes the brain's default mode network, with some changes lasting weeks
Researchers at Washington University School of Medicine in St. Louis published in Nature the most detailed map yet of how psilocybin changes brain network activity in individuals. Instead of scanning many people once, the team scanned a small group of healthy adults roughly 18 times each, before, during and for three weeks after a high dose of psilocybin, and brought them back for a second dose 6 to 12 months later.
Key findings
- Massive desynchronization: psilocybin caused a disruption of functional connectivity that was more than three times larger than that caused by the active control, methylphenidate, at a dose chosen to match psilocybin's physiological effects.
- Default mode network most affected: the largest changes were in the default mode network, the set of regions involved in self-referential thinking, which lost its usual synchrony. Individual brain networks became less distinct from one another.
- Persistent hippocampal change: most changes resolved as the drug wore off, but reduced connectivity between the anterior hippocampus and the default mode network persisted for weeks.
- Experience tracked the brain change: the magnitude of desynchronization correlated with the intensity of the subjective experience, and a task that grounded participants' attention reduced both.
"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."
— Joshua S. Siegel, first author, in the university's press release
Why it matters
The lasting hippocampal-DMN change offers a candidate mechanism for how a single psilocybin session can shift mood and cognition for weeks, the timescale over which clinical trials report antidepressant effects. The authors are cautious: the study was in healthy volunteers, not patients, and the persistence of the change was measured over weeks, not months. Larger patient studies are needed to test whether this measure predicts treatment response.