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Human brain changes after first psilocybin use

Terence J. Lyons, Merle Spriggs, Leevi Kerkelä, Fe Rosas, Leor Roseman, P. Mediano, Carsten Timmermann, Lena Oestreich, Broc A. Pagni, Richard J. Zeifman, Adam Hampshire, William Trender, Hannah Douglass, Manesh Girn, Kate Godfrey, Hannes Kettner, Farnaz Sharif, L Espasiano, Adam Gazzaley, Matthew B. Wall, David Erritzøe, Dj Nutt, Rl Carhart-Harris

October 14, 2024 preprint DOI: 10.1101/2024.10.11.617955 via OpenAlex

Summary

AI-generated from the abstract

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.

Study at a glance

Characteristics Placebo-controlled, within-subjects study
Sample size 28
Population Healthy, entirely psychedelic-naive participants
Intervention Psilocybin
Dose 25 mg
Duration One hour to one month after a single dose
Topics Psilocybin
Keywords Human brain Hallucinogen Neuroscience Psychology
Key finding A single 25 mg dose of psilocybin induced enduring decreases in brain network modularity and axial diffusivity in prefrontal-subcortical tracts, with increased cortical entropy predicting improved well-being one month later.

Abstract

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.

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