Challenges with clinical trial participants in studies with classical psychedelics: A position statement from the National Network of Depression Centers' task group on psychedelics and related compounds.

Clinical trials of classical psychedelics like psilocybin for mental health conditions face unique challenges that may persist if these treatments enter clinical practice. Four categories of challenges with trial participants are identified: treatment nonresponse, expectancy effects and functional unblinding, post-session psychological difficulties, and contagion effects. Management strategies for study teams to mitigate these risks are described. The National Network of Depression Centers and similar organizations can guide best practices to responsibly advance this promising field.

Study at a glance

Abstract

Classical psychedelics-a broad class of compounds that include psilocybin, lysergic acid diethylamide, dimethyltryptamine, and mescaline-have shown significant promise for the treatment of mental health conditions in recent clinical trials. Organizations such as the National Network of Depression Centers (NNDCs) can play a pivotal role in uniting researchers and clinicians working in this field to explore and synthesize existing evidence as well as characterize emerging challenges. We outline several categories of challenges that have emerged in the context of clinical trials with psychedelic drugs, drawing from our collective empirical observations as well as the extant literature. While these challenges have been presented in the context of clinical trial environments, many of them are likely to persist if and when psychedelic treatments become approved and are implemented in psychiatric clinical practice. We describe four categories of challenges in the context of clinical trial participants-(1) treatment nonresponse, (2) expectancy effects and functional unblinding, (3) post-session psychological difficulties, and (4) contagion effects-and provide management strategies for study teams to mitigate associated risks. Classical psychedelics show therapeutic promise as mental health treatments. Studying them properly presents unique and unprecedented challenges that require researchers to develop sophisticated strategies to navigate nonresponse, expectancy effects, functional unblinding, post-session psychological issues, and possible contagion effects to responsibly advance this field. The NNDC and similar organizations are well-positioned to guide best practices and ensure the responsible advancement of this promising field.