Expectations and Motivations for Participation in Clinical Trials Utilizing Psychedelics for Treatment-Resistant Depression: A Qualitative Study.
Christopher Poppe, Liisa Lyck, Laura Bechtold, Dimitris Repantis
Brain and behavior June 1, 2026 Peer reviewed DOI: 10.1002/brb3.71544 via PubMed
Summary
Expectations significantly influence participant experiences in clinical trials, particularly in those with treatment-resistant depression (TRD). In a study involving 17 individuals before and after participation in psychedelic trials using 5-MeO-DMT or psilocybin, motivations such as hope and prior experience were identified, along with expectations regarding symptom reduction and the role of setting. Many viewed participation as a last resort due to chronic illness. The complexity of expectations suggests they may change over time, indicating a need for careful consideration in trial design.
Study at a glance
| Design | qualitative study |
|---|---|
| Sample size | 17 |
| Population | individuals with treatment-resistant depression participating in psychedelic clinical trials |
| Key finding | Expectations in psychedelic trials are complex and may evolve over time, influencing participant experiences. |
Abstract
Expectations strongly shape participant experiences in clinical trials, contributing to placebo effects that complicate interpretation of outcomes. While quantitative tools exist to measure expectations, their subjective and multidimensional nature, especially for individuals with treatment-resistant depression (TRD), remains underexplored. This study aimed to explore the motivations and expectations of participants in psychedelic clinical trials. Seventeen semi-structured interviews were conducted with individuals prior to screening for two TRD clinical trials involving 5-MeO-DMT or psilocybin at a German university hospital. Two matched follow-up interviews were also completed after trial participation. Data were analyzed thematically to identify overarching themes and subthemes. Two main themes emerged: motivations and expectations, each with four subthemes. Motivations included hope, demoralization, prior psychedelic experience, and social motivation. Expectations involved anticipated symptom reduction, perceived mechanisms of change during the psychedelic experience, the role of setting, and retrospective expectations. Many participants viewed trial participation as a last resort due to chronic illness and previous treatment failures. In two cases, retrospective accounts suggested that initially cautious expectations were reinterpreted as stronger after participation. Expectations in psychedelic trials are complex and may evolve over time. These findings highlight the need to systematically address expectancy in trial design, informed consent, and interpretation of clinical outcomes, particularly in treatment-resistant populations.