Psilocybin effects on brain functional connectivity: a systematic review of fMRI studies
Àlvar Farré-colomés, Olga Rublinetska, Óscar Soto-angona
Discover Mental Health March 19, 2026 Peer reviewed DOI: 10.1007/s44192-026-00384-w via OpenAlex
Summary
Psilocybin-assisted therapies show promise for treating depression, but there is limited fMRI evidence explaining the biological mechanisms behind their clinical effects. A review identified 20 datasets, with only 5 involving participants with depression. High dropout rates were noted, and most studies lacked follow-up scans. Key brain regions studied include the amygdala, anterior cingulate cortex, and prefrontal cortex. The literature reveals inconsistencies in methods and highlights the need for further research.
Study at a glance
| Design | review |
|---|---|
| Population | participants diagnosed with depression |
| Key finding | The current literature on psilocybin's effects on the brain is inconsistent and lacks sufficient follow-up data. |
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.