Psilocybin effects on brain functional connectivity: a systematic review of fMRI studies
Àlvar Farré-colomés, Olga Rublinetska, Oscar Soto-Angona
Discover Mental Health March 19, 2026 DOI: 10.1007/s44192-026-00384-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Depression and healthy controls |
| Topics | Default mode network Psilocybin |
| Keywords | Anterior cingulate cortex Dorsolateral prefrontal cortex Functional imaging Functional brain imaging Neuroimaging Dropout neural networks Human studies Data extraction Human brain Magnetic resonance imaging |
| Key findings | The current literature on psilocybin and fMRI exhibits inconsistency in methods and designs, with most research focusing on the amygdala, anterior cingulate cortex, and prefrontal cortex. |
Abstract
Psilocybin-assisted therapies are innovative therapeutic approaches, particularly in the treatment of depression. However, there are sparse studies providing functional magnetic resonance imaging (fMRI) evidence elucidating the underlying biological mechanisms that support clinical outcomes. This review aims to comprehensively gather all the evidence reported in psilocybin studies using fMRI techniques. Independent extraction of articles was conducted by 2 authors using predefined data fields. 20 unique datasets were identified, with 5 including participants diagnosed with depression. Dropout rates were found to be high, and follow-up scanning timepoints were lacking in most of the studies. Most research has focused on the amygdala, the anterior cingulate cortex and the prefrontal cortex, as key regions involved in the effects of psilocybin. However, the current literature exhibits inconsistency in methods and designs. Further research is necessary to better define psilocybin’s impact on the human brain and its potential to enhance psychotherapy outcomes.
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 2
- Multilevel Mechanisms and Clinical Efficacy of Psilocybin in Depression Treatment: A Systematic Review International Journal of Molecular Sciences September 10, 2026
- Stroboscopic light stimulation as a controllable probe of the psilocybin state: a mechanistic framework and a falsifiable prediction Frontiers in Pharmacology September 30, 2026
Cites 62
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
and 57 more in the library