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.
A single high dose of psilocybin (25 mg) produced lasting functional and anatomical brain changes in healthy, psychedelic-naive adults, detected from one hour to one month later. Diffusion imaging showed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity, which in turn correlated with improved well-being. Increased cortical signal entropy shortly after dosing predicted better psychological well-being at one month, with next-day psychological insight mediating this relationship. No such effects occurred with a 1 mg placebo dose. Cognitive flexibility, psychological insight, and well-being also increased at one month.