Five drugs—cannabis, psilocybin, amphetamine, ketamine, and alcohol—were compared for how well they model psychiatric symptoms. Mental health professionals rated how specific certain experiences were to symptom clusters like depression or psychosis. People with personal drug experience then reported how reliably each drug produced those experiences. No experiences were specific to negative or cognitive psychotic symptoms over depression. Psilocybin best modeled positive psychotic symptoms, while acute alcohol and amphetamine best modeled mania. These findings challenge current assumptions about drug models and point to an understudied area needing more research.
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.