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 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| 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 | Hallucinogen Neuroimaging Drug trial Pharmacology Clinical trial |
| Citations | 4 |
| Key points | 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.
Comparable studies
Other randomized controlled trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... | 2006 | Double-blind study | n = 36 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
Citations in the library
Cited by 4
- Psychedelic 5-HT2A receptor agonism alters neurovascular coupling and differentially affects neuronal and hemodynamic measures of brain function Nature Neuroscience October 13, 2025
- Psychedelics disrupt hierarchical cortical propagations in the default mode network of humans and mice. Proceedings of the National Academy of Sciences June 16, 2026
- Psilocybin acutely reduces low-frequency BOLD power and frequency-specific connectivity bioRxiv April 13, 2026
- The Use of Psilocybin in the Treatment of Depressive Disorders: A Narrative Review Cureus January 31, 2026
Cites 28
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
and 23 more in the library