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

Pretreatment clinical characteristics vs dose on the subjective psychedelic experience,

In this secondary analysis of a Phase II trial (n=233) of participants with treatment-resistant depression (TRD) receiving COMP360 psilocybin (1; 10; 25mg) found that dose was the strongest predictor of the subjective psychedelic experience, whilst pretreatment clinical characteristics such as affect, anxiety, and executive functioning contributed only weakly, challenging assumptions about the influence of individual factors on acute psychedelic effects.

“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.“

Notes

Across all measured dimensions of the psychedelic experience, psilocybin dose was the strongest and most consistent predictor of outcomes on both 5D-ASC and EBI scales.

• Higher doses (especially 25 mg) were associated with more intense and qualitatively richer subjective experiences than lower doses.

• In contrast, pretreatment clinical factors generally had much smaller effects.

Interpretation: This result challenges the assumption that individual clinical state prior to treatment (e.g., level of depression, baseline anxiety, executive functioning) is a major determinant of how profoundly someone experiences psilocybin acutely in a controlled clinical setting.

Kirlić, N., Atli, M., Mistry, S., Gold, M., & Goodwin, G. M. (2022). The Relationship Between Participant Pretreatment Clinical Presentation and the Quality of Psilocybin Experience: A Retrospective Analysis. Journal of Clinical Psychopharmacology, 10-1097. Read Paper

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