Neurocognitive effects of psilocybin: A systematic and comprehensive review of neuroimaging studies in humans.
Lucie Berkovitch, Baptiste Fauvel, Katrin H. Preller, Raphaël Gaillard
Neuroscience & Biobehavioral Reviews August 1, 2025 DOI: 10.1016/j.neubiorev.2025.106239 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Sample size | 81 |
| Population | Healthy volunteers and patients with medical conditions |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | EEG Functional connectivity PET Systematic review Psychedelics hallucinogens Entheogens Neuroimaging MRI Brain scanning Brain imaging Neural networks |
| Citations | 8 |
| Key findings | Psilocybin reproducibly impacts neuronal networks such as the default mode network and induces acute and long-lasting functional brain changes associated with subjective and therapeutic effects. |
Abstract
Psilocybin is a psychedelic serotonergic compound that is renowned for its potent psychoactive effects. Over the past 15 years, an increasing number of controlled clinical trials showed that it has a fast-acting and sustainable efficacy in treating various psychiatric disorders. Neuroimaging studies have been conducted with the objective of elucidating the neurobiological mechanisms underlying the subjective and therapeutic effects of psilocybin. However, the diversity of neuroimaging techniques, tasks, and analytical approaches makes it difficult to gain a comprehensive overview of psilocybin's effects on the brain. To address this gap in the literature, we conducted a systematic review in the Medline, Psychinfo and Cochrane databases between January 1, 1990, and May 9, 2025, following PRISMA recommendations. A total of 81 articles met the inclusion criteria. A variety of neuroimaging techniques were employed in small samples of healthy volunteers and patients with medical conditions. The studies investigated the effects of psilocybin on brain activity and connectivity, both at rest and during cognitive tasks. They revealed that psilocybin reproducibly impacted neuronal networks such as the default mode network. However, other findings were more inconsistent. Psilocybin effects on the brain were associated with acute alterations in self-experience, sensory and emotional processing, and sustained effects on mood, personality, and social functioning. In patients with depression, clinical outcomes correlated with brain changes. This review indicates that psilocybin induces acute and long-lasting functional brain changes. While these neuroimaging data require confirmation and further expansion, they shed light on the mechanisms of psilocybin's acute subjective and therapeutic effects in humans.
Comparable studies
Other systematic reviews and meta-analyses on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... | 2020 | Systematic review | n = 188 |
| Blinding and expectancy confounds in psychedelic randomized controlled trials | 2021 | Systematic review | |
| Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Patients from included clinical trials | 2016 | Systematic review | |
| The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis People with elevated symptoms of anxiety and depression | 2020 | Meta-analysis | n = 117 |
| Default Mode Network Modulation by Psychedelics: A Systematic Review Participants from included studies | 2022 | Systematic review |
Citations in the library
Cited by 11
- Psychedelics in NHS services: exploring a model for real-world implementation of psilocybin The British Journal of Psychiatry March 30, 2026
- A Randomised, Triple-Blind, Dose-Finding Study of the Impact of Psilocybin on Motor Function in Healthy Participants medRxiv December 23, 2025
- Global Increases in Brain Glucose Metabolism Following Acute N,N-Dimethyltryptamine and Harmine Administration in Healthy Volunteers: An [¹⁸F]FDG-PET Study Research Square July 27, 2025
- Psilocybin in Treatment-Resistant Depression: Weighing Rapid Antidepressant Effects Against Uncertain Durability Therapeutics October 19, 2026
- Preclinical Anxiolytic- and Antidepressant-like Effects of α,α-Trehalose, a Bioactive Compound Identified in Psilocybe cubensis Molecules September 23, 2026
and 6 more in the library
Cites 164
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- 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
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
and 159 more in the library