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 Peer reviewed DOI: 10.1038/s41467-026-71962-3 via PubMed
Summary
A single high dose of 25 mg psilocybin in 28 healthy, psychedelic-naive participants led to increased cognitive flexibility, psychological insight, and well-being one month later. While some anatomical changes were observed, such as decreased axial diffusivity in specific brain tracts, enduring functional brain changes were largely absent. Increased cortical signal entropy shortly after dosing predicted improved well-being, with next-day psychological insight playing a mediating role. No effects were noted with a placebo.
Study at a glance
| Design | placebo-controlled, within-subjects |
|---|---|
| Sample size | 28 |
| Population | healthy, psychedelic-naive participants |
| Key finding | Increases in cognitive flexibility, psychological insight, and well-being were observed one month after a single high dose of psilocybin. |
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.