Human brain changes after first psilocybin use.
T Lyons, M Spriggs, L Kerkelä, Fernando E. Rosas, Leor Roseman, Pedro A. M. Mediano, C Timmermann, Lena K L Oestreich, Broc A. Pagni, R J Zeifman, Adam Hampshire, William Trender, Hannah Douglass, Manesh Girn, Kate Godfrey, Hannes Kettner, F Sharif, L Espasiano, Adam Gazzaley, Matthew B. Wall, David Erritzøe, D J Nutt, R L Carhart-Harris
Nature Communications May 5, 2026 DOI: 10.1038/s41467-026-71962-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 |
| Topics | Psilocybin |
| Citations | 19 |
| Key points | 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.
Comparable studies
Other randomized controlled trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... | 2006 | Double-blind study | n = 36 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
Citations in the library
Cited by 18
- From relaxed beliefs under psychedelics (REBUS) to revised beliefs after psychedelics (REBAS). Scientific Reports January 29, 2025
- Single-dose (10 mg) psilocybin reduces symptoms in adults with obsessive-compulsive disorder: A pharmacological challenge study. Comprehensive Psychiatry July 1, 2025
- The entropic heart: Tracking the psychedelic state via heart rate dynamics bioRxiv (Cold Spring Harbor Laboratory) November 9, 2023
- The science of psychedelic medicine. Nature Medicine February 6, 2026
- Enhanced meaning in life following psychedelic use: converging evidence from controlled and naturalistic studies Frontiers in Psychology June 6, 2025
and 13 more in the library
Cites 44
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
and 39 more in the library