Human brain changes after first psilocybin use.
Level 2 - randomized trial
Placebo-controlled, within-subjects trial in humans
PubMed 42086570 · doi:10.1038/s41467-026-71962-3
What was done
An exploratory, placebo-controlled, within-subjects study in 28 healthy, psychedelic-naive participants measured anatomical and functional brain changes from 1 hour to 1 month following a single 25 mg dose of psilocybin versus a 1 mg psilocybin placebo control. Assessments included electroencephalography (EEG), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and measures of cognitive flexibility, psychological insight, and well-being.
What was found
The abstract reports no exact numerical values, effect sizes, or test statistics. It reports that 1 month after 25 mg psilocybin, participants showed increases in cognitive flexibility, psychological insight, and well-being. DTI revealed decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlated with decreased brain network modularity on fMRI over the month. Enduring functional brain changes were largely absent, but network modularity decreases correlated with well-being increases. Increased cortical signal entropy on EEG at 1 and 2 hours post-dosing predicted improved well-being at 1 month, mediated by next-day psychological insight. No such effects were observed with the 1 mg placebo.
Why it matters
This trial provides within-subject evidence that a single high dose of psilocybin can induce month-long microstructural tract changes and acute cortical entropy shifts that relate to sustained psychological improvements in healthy individuals.
Limits
The sample size is small (n = 28), and the cohort was limited to healthy, psychedelic-naive volunteers, limiting generalizability to clinical populations. The abstract presents no numerical effect sizes or confidence intervals. Long-term functional brain changes were largely absent, and reported brain-behavior relationships rely on exploratory correlational and mediation analyses.
Cited by
- supports A diffusion tensor imaging preprint by Lyons et al. shows changes in prefrontal white matter tracts following a single dose of psilocybin.