Human brain changes after first psilocybin use.
Nature communications May 5, 2026 T Lyons, M Spriggs, L Kerkelä et al. 19 citations
A single high dose of psilocybin (25 mg) in 28 healthy, psychedelic-naive participants produced anatomical and functional brain changes lasting from one hour to one month. At one month, participants showed increased cognitive flexibility, psychological insight, and well-being. Diffusion tensor imaging revealed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity. Decreased modularity negatively correlated with increased well-being, consistent with depression findings. Increased cortical signal entropy one to two hours after dosing predicted improved well-being at one month, mediated by next-day psychological insight. No effects occurred with a 1 mg placebo dose.