Current Understanding on Psilocybin for Major Depressive Disorder: A Review Focusing on Clinical Trials
Sheng-Min Wang1,2, Sunghwan Kim1,2, Won-Seok Choi1,2, Hyun Kook Lim1,2, Young Sup Woo1,2, Chi-Un Pae1,3, Won-Myong Bahk1,2
1Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea
2Department of Psychiatry, Yeouido St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
3Department of Psychiatry, Bucheon St. Mary’s Hospital, The Catholic University of Korea, Bucheon, Korea
Correspondence to: Won-Myong Bahk
Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 10 63-ro, Yeongdeungpo-gu, Seoul 07345, Korea
Received: September 28, 2023; Revised: October 22, 2023; Accepted: October 23, 2023; Published online: November 30, 2023.
© The Korean College of Neuropsychopharmacology. All rights reserved.

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Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a “breakthrough therapy” for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin’s potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials [DB-RCTs]) trials exploring psilocybin’s impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over six months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.
Keywords: Psychedelics; Psilocybin; Depression; Treatment.

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