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

Summary

A systematic examination of registered interventional trials involving DMT, ayahuasca, and their combination identified 26 eligible trials. Most were early-stage phase I studies, primarily focused on DMT alone, with over half completed. Eligibility criteria favored medically healthy adults, emphasizing safety and physiological monitoring rather than disorder-specific outcomes. While some publications suggest potential clinical effects for depression, the field is still developing foundational knowledge and has limited programs targeting specific disorders 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.