Current Understanding on Psilocybin for Major Depressive Disorder: A Review Focusing on Clinical Trials
Sunghwan Kim, Won-Seok Choi, Hyun Kook Lim, Young Sup Woo, Sheng‐min Wang, Chi‐un Pae, Won‐myong Bahk
Clinical Psychopharmacology and Neuroscience November 30, 2023 DOI: 10.9758/cpn.23.1134 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Double-blind Open-label Pilot study Peer reviewed |
|---|---|
| Intervention | Psilocybin |
| Dose | 25 mg, 10 mg, 1 mg |
| Topics | Anxiety Depression Psilocybin |
| Keywords | Antidepressant Randomized controlled trial Placebo Hallucinogen Pharmacology |
| Citations | 16 |
| Key findings | Psilocybin shows promise in treating depression and anxiety, with notable safety profiles, based on a review of eleven clinical trials. |
Abstract
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.
Comparable studies
Other narrative reviews on psilocybin for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics as anti-inflammatory agents Animal models and cellular studies | 2018 | Review | |
| Ayahuasca: Pharmacology, neuroscience and therapeutic potential | 2016 | Review | |
| Psychedelic Drugs in Biomedicine | 2017 | Review | |
| A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses | 2020 | Review | |
| Psychedelics and health behaviour change | 2021 | Review |
Citations in the library
Cited by 11
- An overview of psilocybin, LSD, MDMA, and ketamine in revitalizing psychedelic-assisted therapy: Insights, limitations and future directions. Progress in Neuro-Psychopharmacology and Biological Psychiatry July 25, 2025
- Effect of psilocybin therapy on suicidal ideation, attempts, and deaths in people with psychiatric diagnoses: a systematic review and meta-analysis Therapeutic Advances in Psychopharmacology September 1, 2025
- 5-HT1B receptor activation produces rapid antidepressant-like effects in rodents. Pharmacology, Biochemistry, and Behavior February 1, 2025
- Psilocybin's effects on obsessive-compulsive behaviors: A systematic review of preclinical and clinical evidence Psychedelics October 28, 2025
- Towards "unmakable" psychedelics: SAR exploration of psilocin analogs obtained by a HATU-mediated amide coupling strategy European Journal of Medicinal Chemistry Reports June 3, 2025
and 6 more in the library
Cites 29
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
and 24 more in the library