Psychiatry and clinical neurosciencesFeb 26, 2026

Psilocybin’s use in mental health: History, clinical studies, brain imaging, and rules

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Feb 27, 2026

Abstract

Psilocybin has shown therapeutic effects in clinical trials for major depressive disorder (MDD) and certain substance use disorders.

Historical use of psilocybin includes spiritual and healing rituals before facing legal restrictions in the 1970s.
Research interest in psilocybin has revived since the 1990s, leading to studies that suggest its potential for treating psychiatric disorders.
Current phase III clinical trials are exploring psilocybin's effectiveness in treating depression, though data for obsessive-compulsive disorder and bipolar depression are limited.
Short-term side effects from psilocybin are generally mild and temporary, while long-term effects require further research.
Neuroimaging studies are currently limited to major depressive disorder, with ongoing trials expanding to other psychiatric conditions.
Regulatory acceptance of psilocybin varies, with some regions allowing controlled use while others maintain strict prohibitions.

Simplified

Psilocybin, a classic psychedelic compound, has garnered renewed interest as a potential treatment for various psychiatric disorders. This review provides a comprehensive overview of psilocybin's history, recent clinical evidence, ongoing clinical trials, neuroimaging findings, and regulations. Historically used in spiritual and healing rituals, psilocybin was in the early 1970s subjected to strict legal restrictions that stalled research for decades. However, renewed scientific interest began in the 1990s, with studies demonstrating psilocybin's therapeutic potential for psychiatric disorders. Clinical trials have reported therapeutic effects of psilocybin in major depressive disorder (MDD), depressive symptoms associated with life-threatening illnesses, and in some substance use disorders. Moreover, several phase III clinical trials of psilocybin for depression are currently underway, though trial data for obsessive-compulsive disorder and bipolar depression are limited. Short-term side effects are reportedly generally mild and transient, but long-term effects still need further investigation. Neuroimaging research using magnetic resonance imaging and electroencephalography is still limited and focuses mainly on MDD. However, ongoing clinical trials include neuroimaging studies for psychiatric disorders beyond MDD, as well as positron emission tomography studies for MDD. Regulatory frameworks vary internationally. While many countries continue to classify psilocybin as a prohibited substance, use of psilocybin under controlled conditions is now permitted in Switzerland, parts of the United States, Canada, and Australia. Despite encouraging data, challenges remain, including the need for larger, blinded trials, standardized protocols, and clarification of long-term efficacy and safety. Psilocybin represents a novel therapeutic approach in psychiatric treatment, warranting further rigorous scientific and regulatory research.

Psilocybin’s use in mental health: History, clinical studies, brain imaging, and rules

Abstract

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