Human Brain Changes After First Psilocybin Use

New multimodal imaging research reveals how a single high dose of psilocybin may influence brain connectivity, cognitive flexibility, and psychological well-being in psychedelic-naive participants.

Authors: 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, and R. L. Carhart-Harris

Published in Nature Communications, this exploratory placebo-controlled neuroimaging study investigated the acute and long-term brain effects of first-time psilocybin use in healthy psychedelic-naive participants. Using EEG, functional MRI (fMRI), and diffusion tensor imaging (DTI), researchers evaluated how a single 25 mg dose of psilocybin influenced brain activity, network organization, white matter structure, cognitive flexibility, psychological insight, and well-being over the course of one month.

The study identified acute increases in cortical signal entropy and decreases in alpha power during the psychedelic experience, alongside measurable improvements in psychological well-being and cognitive flexibility one month later. Researchers also observed changes in prefrontal-subcortical white matter tracts and brain network modularity, offering new insight into the potential neurobiological mechanisms associated with psychedelic-assisted therapies.

This publication contributes to the growing body of translational neuroscience research exploring how advanced neuroimaging and multimodal biomarker strategies can help characterize both acute pharmacodynamic effects and longer-term functional brain changes associated with psychedelic compounds.

Why read this article

• How EEG-based measures of brain entropy may predict psychological insight and well-being outcomes
• Evidence of changes in white matter diffusivity and brain network modularity following psilocybin exposure
• Relationships between psychedelic-induced brain activity, cognitive flexibility, and emotional processing
• The role of multimodal neuroimaging in advancing translational psychedelic research and biomarker development
• Implications for future CNS drug development and psychedelic-assisted therapy research

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