Registered Clinical Trials of Ayahuasca and DMT: A Scoping Review.

The clinical trial landscape for ayahuasca and DMT expanded rapidly after 2020-2021, dominated by early-stage development. Most trials are phase I, primarily sponsored by academic or hospital institutions, and focus on DMT-only administration. Eligibility criteria are conservative, enrolling medically and psychiatrically healthy adults with extensive cardiovascular and psychiatric exclusions. Primary outcomes prioritize acute safety, physiological monitoring, and characterization of subjective altered-states, while disorder-specific symptom endpoints are less common. Publications from depression-focused trials provide preliminary evidence of potential clinical effects, but the field remains constrained by a limited number of indication-specific programs beyond depression.

Study at a glance

Abstract

Interest in ayahuasca and its main component, N,N-Dimethyltryptamine (DMT), has currently moved from historical and experimental use into modern clinical development. Yet, current evidence is fragmented, and systematic mapping of trial methods and design choices remains limited. We therefore systematically examined registered interventional trials of DMT, ayahuasca, and DMT combined with harmine on ClinicalTrials.gov, identifying 26 eligible trial registers for review. We extracted and harmonized trial characteristics, participant eligibility and enrollment patterns, design features, administration routes, and registered outcomes, and linked completed registrations to associated publications. The registry landscape expanded after 2020-2021 and was dominated by early-stage development, with most trials in phase I and more than half listed as completed at the time of extraction. Trials were primarily DMT-only and most often sponsored by academic or hospital institutions. Eligibility criteria were conservative, emphasizing medically and psychiatrically healthy adult cohorts and extensive cardiovascular and psychiatric exclusions. Accordingly, primary outcomes prioritized acute safety and physiological monitoring, alongside structured characterization of the subjective and altered-states profile, while disorder-specific symptom endpoints were less commonly prioritized as primary objectives. Publications linked to included trials largely reflect this early-stage focus, describing controlled administration, tolerability limits, route and formulation refinement, and initial mechanistic readouts. A smaller set of publications from depression-focused trials provides preliminary evidence of potential clinical effects, supporting further controlled replication and broader disorder-focused development. Overall, registered trials indicate an active and maturing field that has generated foundational safety and regimen knowledge, but remains constrained by a limited number of indication-specific programs beyond depression.