The Relationship Between Participant Pretreatment Clinical Presentation and the Quality of Psilocybin Experience
Namik Kirlic, Merve Atli, Sunil Mistry, Michael C. Gold, Guy M. Goodwin
Journal of Clinical Psychopharmacology December 9, 2025 DOI: 10.1097/jcp.0000000000002119 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 233 |
| Population | Adults with treatment-resistant depression |
| Intervention | COMP360 psilocybin |
| Dose | 25, 10, or 1 mg |
| Duration | Single dose |
| Topics | Psilocybin |
| Keywords | Presentation obstetrics Quality philosophy Medline Hallucinogen Clinical psychology Psychotherapist |
| Registration | NCT03775200 |
| Key findings | Dose was the strongest and most consistent predictor of the psychedelic experience, while pretreatment characteristics contributed only weakly. |
Abstract
Purpose/Background: The therapeutic effects of psilocybin treatment are thought to be influenced by the subjective dose-dependent psychedelic experience, as well as the individual participant’s mindset and the treatment environment. However, the relative contribution of an individual’s pretreatment clinical characteristics and their subjective psychedelic experience remains unclear. We examined the relationship between pretreatment participant factors and the acute effects of COMP360 psilocybin. Methods/Procedures: Participants (N=233) with treatment-resistant depression received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a synthesized, pharmaceutical-grade, proprietary formulation of psilocybin, developed by the sponsor, Compass Pathfinder Ltd., a subsidiary of Compass Pathways plc: ClinicalTrials.gov, NCT03775200). The psychedelic experience was assessed by the Five-Dimensional Altered States of Consciousness questionnaire (5D-ASC) and Emotional Breakthrough Inventory (EBI). We used hierarchical regression to measure the relative contribution of pretreatment clinical characteristics (along the cognitive-affective, somatic, and functional impairment domains) in addition to the drug dose to the subjective psychedelic experience. Findings/Results: Dose was the strongest and most consistent predictor of the psychedelic experience. Some pretreatment characteristics contributed weakly to subjective experiences. Positive affect, lower generalized anxiety symptoms, higher executive functioning, and greater personality disorder symptoms had significant effects on different aspects of the subjective psychedelic experience. Implications/Conclusions: These findings challenge the assumption that pretreatment characteristics are major determinants of the acute psychedelic experience. While some traits may modestly modulate aspects of the experience, dose remains the largest driver.
Comparable studies
Other randomized controlled trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety | 2016 | Randomized controlled trial | n = 51 |
| Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression | 2016 | Double-blind, placebo-controlled, crossover trial | n = 29 |
| Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Hallucinogen-naïve adults reporting regular participation in religious or spiritual... | 2006 | Double-blind study | n = 36 |
| Trial of Psilocybin versus Escitalopram for Depression Selected group of patients with depression | 2021 | Randomized controlled trial | |
| Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder Adults aged 21 to 75 years with major depressive disorder, not currently using... | 2020 | Randomized controlled trial | n = 24 |
Citations in the library
Cites 35
- 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
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
and 30 more in the library