Human brain changes after first psilocybin use.
T Lyons, M Spriggs, L Kerkelä, F E Rosas, L Roseman, P A M Mediano, C Timmermann, L Oestreich, B A Pagni, R J Zeifman, A Hampshire, W Trender, H M Douglass, M Girn, K Godfrey, H Kettner, F Sharif, L Espasiano, A Gazzaley, M B Wall, D Erritzoe, D J Nutt, R L Carhart-Harris
Nature communications May 5, 2026 DOI: 10.1038/s41467-026-71962-3 via PubMed
Summary
AI-generated from the abstractA 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.
Study at a glance
| Characteristics | Exploratory, placebo-controlled, within-subjects study Peer reviewed |
|---|---|
| Sample size | 28 |
| Population | Healthy, entirely psychedelic-naive participants |
| Intervention | Psilocybin |
| Dose | 25 mg |
| Duration | One-hour to one-month post-dosing |
| Citations | 19 |
| Key finding | A single 25 mg dose of psilocybin induces lasting anatomical and functional brain changes, including decreased axial diffusivity in prefrontal-subcortical tracts and reduced network modularity, with increased cortical entropy predicting improved well-being at one month. |
Abstract
Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown. In an exploratory, placebo-controlled, within-subjects, electroencephalography (EEG), and magnetic resonance imaging (MRI) study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes are detected from one-hour to one-month after a single high-dose (25 mg) of psilocybin. Increases in cognitive flexibility, psychological insight, and well-being are seen at one-month. Diffusion tensor imaging (DTI) done before and one-month after 25 mg psilocybin reveals decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlate with decreases in brain network modularity (fMRI) over the same month. Enduring functional brain changes are largely absent, but network modularity change (numerical decrease) negatively correlates with well-being change (significant increase), in line with previous findings in depression. Increased cortical signal entropy (EEG) at 1- and 2-hours post-dosing predicts improved psychological well-being at one-month. Next-day psychological insight mediates the entropy to well-being relationship. All effects are exclusive to 25 mg psilocybin; no effects occur with a 1 mg psilocybin placebo.