Brain entropy during a first psilocybin trip predicts later gains in psychological insight and well-being, while lasting brain changes remain limited

A small exploratory study of 28 psychedelic-naive healthy adults found that a single 25-milligram dose of psilocybin increased brain entropy, or the irregularity and unpredictability of electrical activity, during the acute psychedelic experience. Greater entropy was associated with more psychological insight the next day and larger improvements in well-being one month later, while participants also showed gains in cognitive flexibility. However, most measures of lasting brain function changed little and were not statistically significant. Diffusion imaging suggested possible alterations in white matter pathways connecting the prefrontal cortex with deeper brain regions, but the biological meaning of this finding is uncertain and another analysis did not reproduce it. The fixed low-dose-then-high-dose design, modest sample, exploratory analyses, and limited protection against false positives mean the results require replication in larger randomized studies.