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Psilocybin’s acute and persistent brain effects: a precision imaging drug trial

Subha Subramanian, Travis Rick Renau, Demetrius Perry, Karin Flavin, Christine Horan, Ravi V. Chacko, Timothy O. Laumann, Julia Schweiger, Nicholas V. Metcalf, Eric J. Lenze, Abraham Z. Snyder, Nico U.f. Dosenbach, Ginger E. Nicol, Joshua S. Siegel

Scientific Data June 5, 2025 DOI: 10.1038/s41597-025-05189-0 via OpenAlex

Summary

AI-generated from the abstract

A psychedelic drug, psilocybin, and a comparison drug, methylphenidate, produce distinct acute and persistent changes in brain networks measurable with precision functional mapping, a technique that improves signal detection by repeatedly scanning individuals. Seven healthy adults underwent extensive baseline brain imaging, imaging shortly after drug intake, and follow-up scans for up to two weeks. Four participants repeated the psilocybin protocol months later. The dataset includes resting-state and task-based functional MRI, structural scans, and subjective experience reports. The authors release this resource to help researchers study how psilocybin and methylphenidate alter brain network organization over time.

Study at a glance

Characteristics Randomized cross-over study Open-label Longitudinal Peer reviewed
Sample size 7
Population Healthy volunteers
Interventions Psilocybin Methylphenidate
Duration Imaging beginning 60-90 minutes after drug exposure, longitudinal imaging for up to two weeks after drug exposure
Topics Psilocybin
Keywords Neuroscience Hallucinogen Neuroimaging Drug trial
Citations 4
Key finding Precision functional mapping can characterize acute and persistent effects of psilocybin and methylphenidate on brain networks in individual participants.

Abstract

Psilocybin (PSIL) is a psychedelic drug and a promising experimental therapeutic for many psychiatric conditions. Precision functional mapping (PFM) combines densely repeated resting state fMRI sampling and individual-specific network mapping to improve signal-to-noise ratio (SNR) and effect size in brain imaging research. We present a randomized cross-over study in which PFM was used to characterize acute and persistent effects of psilocybin or methylphenidate (MTP) on brain networks. Seven healthy volunteers (mean age 34.1 years, SD = 9.8; n = 3 females, n = 6 Caucasians) underwent (1) extensive baseline imaging, (2) imaging beginning 60-90 minutes after drug exposure, and (3) longitudinal imaging for up to two weeks after drug exposure. Four individuals also participated in an open-label PSIL replication protocol over 6 months later. This dataset includes resting state (using advanced high-resolution multi-echo fMRI), task fMRI, structural, and diffusion basis spectral imaging as well as assessments of subjective experience. We are releasing this unique dataset as a resource for neuroscientists to study the acute and persistent effects of PSIL and MTP on brain networks.

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