Treatment Expectation is the Strongest Predictor of Willingness to Participate in Psychedelic Clinical Trials

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, however these non-pharmacological variables may also influence the initial decision to participate. 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 their interest in participating in a psychedelic clinical trial and the Big Five personality traits. A subset (N = 235) were re-surveyed for additional data on psychological flexibility and outcome expectations. Logistic regression analyses were conducted to measure the associations between these factors and participants’ 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 predicted lower willingness. When controlling for all variables, negative expectancy emerged as the strongest and only significant predictor.Conclusions: The results show that negative outcome expectations play a role in who chooses to participate in psychedelic clinical trials, suggesting that current trials are biased toward including participants who are more risk tolerant. As psychedelic therapies enter mainstream medical practice, broader populations undergoing psychedelic treatment may not see the same therapeutic outcomes observed in current trials. These findings highlight the need to account for expectancy effects in study enrollment to prevent overestimation of efficacy and improve generalizability.Keywords: psychedelics, willingness to participate, expectations, personality, openness