How Psilocybin Changes Brain Connectivity and Blurs Inner and Outer Worlds

Half of the participants ranked their session among the most meaningful experiences of their lives, while 24 placed it among their personal top five. Storchier and his colleagues began analyzing brain-scan data to understand why.

Psilocybin shifts the balance between sensory and association brain regions

Researchers measured global functional connectivity, which describes how much influence each area of the cortex has on the rest of the brain. When participants closed their eyes, the researchers observed less “wobbling” in sensory areas and more in association areas.

“The brain’s ability to construct reality, imagination, or associations, beliefs, and a sense of self seems to have an upper hand over sensory areas,” Stryker said, emphasizing that this interpretation remains hypothetical. “This may help explain why people have meaningful and complex image experiences, and why they use personally relevant images to have mystical experiences.”

The team also found that connections within each brain network weakened, while connections between networks strengthened. Brain modularity—a measure of how effectively neurons are organized into specialized teams—decreased across all four parts of the experimental sequence.

In addition, brain activity with the eyes closed looked very different from activity recorded while participants watched a movie when they were sober. Under psilocybin, that difference nearly disappeared. Visual networks reduced the difference in connectivity between eyes-open and eyes-closed states by 85%.

Independent EEG results supported the finding. Alpha-band activity, a brain signal that typically helps gate visual input, fell by nearly half.

“When someone takes a psychedelic drug, they can close their eyes and see complex images, and the boundaries between the inner and outer worlds seem to be blurred more than we normally experience,” Stryker said.

Finding hidden order in psychedelic brain activity

Overall, the findings reproduced the disruptions in brain activity that many researchers associate with psychedelics. However, the apparent chaos became more ordered when the team processed the data using a slightly unconventional approach.

Scientists typically perform two types of averaging in standard brain-imaging studies. The first averages activity over time. An eight-minute brain scan contains hundreds of sequential images of the entire brain. To assess how two regions interact, researchers traditionally average those images into a single number indicating how closely the regions’ activity matches across the full scan.