Psilocybin for psychiatric disorders: History, clinical trials, neuroimaging, and regulations
Kengo Yonezawa, Mika Hirata, Hiroaki Takano, Keisuke Kusudo, Sota Tomiyama, Lisa Harada, Kota Suzuki, Dj Nutt, Hiroyuki Uchida, Hideaki Tani
Psychiatry and Clinical Neurosciences February 26, 2026 DOI: 10.1111/pcn.70042 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Patients with MDD and other psychiatric disorders |
| Topics | Depression Psilocybin |
| Keywords | Clinical trial Hallucinogen Depression economics Functional neuroimaging Psychotherapist Bipolar disorder |
| Citations | 1 |
| Key findings | Psilocybin shows therapeutic potential for major depressive disorder, depressive symptoms in life-threatening illnesses, and some substance use disorders, but larger blinded trials and standardized protocols are needed. |
Abstract
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.