The Relationship Between Participant Pretreatment Clinical Presentation and the Quality of Psilocybin Experience: A Retrospective Analysis

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.