Skip to content

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 DOI: 10.1002/brb3.71544 (opens in new tab)

Read Full Text
Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Qualitative study Peer reviewed
Sample size 17
Population Individuals with treatment-resistant depression prior to screening for two psychedelic clinical trials at a German university hospital
Topics Depression
Keywords Clinical trials Expectations Motivation Psychedelic treatments
Citations 1
Key findings Expectations in psychedelic trials for treatment-resistant depression are multidimensional, evolve over time, and may be reinterpreted after participation.

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.

Comparable studies

Other qualitative studies on depression, most cited first.

Study Year Design Participants
Patients’ Accounts of Increased “Connectedness” and “Acceptance” After Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression enrolled in an open-label trial of psilocybin 2017 Qualitative study n = 20
An exploratory mixed methods study of the acceptability and effectiveness of mindfulness -based cognitive therapy for patients with active depression and anxiety in primary care Primary care patients with recurrent depression or recurrent depression and anxiety 2006 Exploratory mixed methods study n = 13
A qualitative study of mindfulness‐based cognitive therapy for depression Participants in mindfulness-based cognitive therapy in a mental-health context 2001 Qualitative study n = 7
Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency? 2017 Qualitative review
Abnormal Time Experiences in Major Depression: An Empirical Qualitative Study Patients affected by affective and schizophrenic disorders 2016 Qualitative study n = 550

Citations in the library

Cited by 1

Cites 16

and 11 more in the library

Related reading

Explore topics

Depression 5-MeO-DMT DMT Psilocybin