Human brain changes after first psilocybin use
In a placebo-controlled, within-subject neuroimaging study of 28 psychedelic‑naive participants, a single high (25 mg) dose of psilocybin produced lasting functional and anatomical brain changes from 1 hour to 1 month and improved cognitive flexibility, psychological insight and well‑being at one month. Diffusion MRI showed decreased axial diffusivity in prefrontal–subcortical tracts that correlated with reduced brain network modularity (which correlated with improved well‑being), acute increases in cortical signal entropy predicted one‑month well‑being via next‑day psychological insight, and none of these effects were seen with a 1 mg control dose.
Authors
- Fernando Rosas
- Richard Zeifman
- Robin Carhart-Harris
Published
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 unknown. In a placebo-controlled, within-subjects, electroencephalography, and magnetic resonance imaging study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes were 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 were seen at one-month. Diffusion imaging done before and one-month after 25mg psilocybin revealed decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlated with decreased brain network modularity over the same time period. Decreased modularity also correlated with improved well-being. Increased cortical signal entropy at 1– and 2-hours post-dosing predicted improved psychological well-being at one-month. Next-day psychological insight mediated the entropy to well-being relationship. All effects were exclusive to 25mg psilocybin; no effects occurred with a 1mg psilocybin ‘placebo’ dose.
Research Summary of 'Human brain changes after first psilocybin use'
Introduction
Lyons and colleagues frame the study around the question of whether single high doses of psilocybin produce enduring anatomical and functional brain changes in humans. Previous work has established that psychedelics produce robust acute effects on brain function and can produce long-term psychological changes, and preclinical studies suggest 5-HT2A receptor agonism may be linked to structural plasticity. However, long-term in vivo human neuroimaging evidence is limited and inconsistent, especially in healthy, psychedelic-naive volunteers. To address this gap, the investigators performed a multi-modal within-subjects study combining electroencephalography (EEG), functional MRI (fMRI) and diffusion tensor imaging (DTI) in healthy volunteers receiving their first-ever high-dose (25 mg) oral psilocybin. A fixed-order repeated-measures design was used: participants first received a 1 mg psilocybin 'placebo' dose and, one month later, a 25 mg dose. Brain and behavioural outcomes were assessed at baseline, during dosing (EEG) and at one month post-dosing (MRI and behavioural measures), with the aim of identifying acute-to-longer-term neural changes and their relationships to psychological outcomes such as insight and well-being.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Lyons, T., Spriggs, M., Kerkelä, L., Rosas, F., Roseman, L., Mediano, P., Timmermann, C., Oestreich, L., Pagni, B., Zeifman, R., Hampshire, A., Trender, W., Douglass, H., Girn, M., Godfrey, K., Kettner, H., Sharif, F., Espasiano, L., Gazzaley, A., . . . Carhart-Harris, R. (2024). Human brain changes after first psilocybin use. https://doi.org/10.1101/2024.10.11.617955
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Agnorelli, C., Spriggs, M. J., Godfrey, K. et al. · Preprints (2024)
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