Treatment expectation is associated with willingness to participate in a psychedelic clinical trial
Anna Paige Payton, Josie Flohr, Boris D. Heifets, Pilleriin Sikka
Journal of Psychedelic Studies October 21, 2026 DOI: 10.1556/2054.2026.00498 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort (survey) Peer reviewed |
|---|---|
| Sample size | 988 |
| Population | Chronic pain patients |
| Key findings | Openness to experience and positive outcome expectations were associated with greater willingness to participate in a psychedelic trial, while negative outcome expectations were linked to lower willingness; with all variables controlled, negative expectancy was the strongest and only significant predictor. The authors argue this may bias trial samples toward risk-tolerant, positively expectant participants, potentially overestimating efficacy and limiting external validity. |
Abstract
Abstract: Background and
Aims: Understanding the factors that lead to participation in psychedelic clinical trials is essential for assessing potential biases in enrollment and ensuring the generalizability of findings. Psychedelic treatment is thought to impact personality traits, psychological flexibility, and expectations, yet the role of these non-pharmacological variables in the initial decision to participate has not been studied. This study aimed to identify factors associated with the willingness to participate in a psychedelic trial.
Methods: A cohort of chronic pain patients ( N = 988) completed a survey assessing interest in participating in a psychedelic clinical trial and the Big Five personality traits. A subset ( N = 235) was re-surveyed for additional data on psychological flexibility and outcome expectations. Binary logistic regression analyses examined associations between these factors and willingness to participate.
Results: Trait openness to experience and positive outcome expectations, were associated with a greater likelihood of willingness to participate, while negative outcome expectations were linked with a lower likelihood. When controlling for all variables, negative expectancy emerged as the strongest and only significant predictor.
Conclusions: The results suggest that outcome expectations may play a role in who chooses to participate in psychedelic trials. This potential bias toward including participants who are more risk tolerant and hold more positive treatment expectations may lead to overestimated efficacy estimates and limits the external validity of trial findings. Understanding who chooses to participate in psychedelic research, and who does not, may be as important for the field as understanding who responds to treatment.