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  3. Human Brain Changes After First Psilocybin Use.
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  3. Human Brain Changes After First Psilocybin Use.

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Human brain changes after first psilocybin use.

T Lyons1, M Spriggs1, L Kerkelä2

  • 1Division of Psychiatry, Department of Brain Sciences, Centre for Psychedelic Research, Imperial College London, London, UK.

Nature Communications
|May 5, 2026

View abstract on PubMed

Summary
This summary is machine-generated.

A single high dose of psilocybin may induce lasting brain changes, enhancing cognitive flexibility and well-being. These effects, observed over a month, correlate with altered brain network connectivity in psychedelic-naive individuals.

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Area of Science:

  • Neuroscience
  • Psychopharmacology
  • Neuroimaging

Background:

  • Psychedelics profoundly impact brain function and behavior, but their potential for enduring anatomical and functional changes remains under-explored.
  • Understanding these long-term effects is crucial for therapeutic applications and safety assessments.

Purpose of the Study:

  • To investigate enduring anatomical and functional brain changes following a single high dose of psilocybin in psychedelic-naive individuals.
  • To explore the relationship between neuroimaging findings and psychological outcomes over a one-month period.

Main Methods:

  • An exploratory, placebo-controlled, within-subjects study involving 28 healthy, psychedelic-naive participants.
  • Utilized electroencephalography (EEG), magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI) before and up to one month after psilocybin administration.
  • Assessed cognitive flexibility, psychological insight, and well-being at one-month post-dose.

    • Main Results:

    • Psilocybin (25 mg) administration led to increased cognitive flexibility, psychological insight, and well-being at one month.
    • Diffusion tensor imaging revealed decreased axial diffusivity in prefrontal-subcortical tracts, correlating with reduced brain network modularity.
    • Increased cortical signal entropy (EEG) at 1-2 hours post-dose predicted improved one-month well-being, mediated by next-day psychological insight.

    Conclusions:

    • A single high dose of psilocybin can induce lasting neuroanatomical and functional brain changes, alongside significant psychological benefits.
    • Decreased brain network modularity was associated with reduced psychological well-being, consistent with findings in depression.
    • Cortical signal entropy post-psilocybin may serve as a predictor for long-term psychological outcomes.