Registered Clinical Trials of Ayahuasca and DMT: A Scoping Review.
Tijana Stojanovic, Kent W Nilsson, Robert Fredriksson, Helgi B Schiöth, Thiago C. Moulin
Clinical Pharmacology & Therapeutics July 1, 2026 DOI: 10.1002/cpt.70311 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Sample size | 26 |
| Population | Registered interventional trials of DMT, ayahuasca, and DMT combined with harmine on ClinicalTrials.gov |
| Topics | Ayahuasca DMT |
| Key findings | The registry landscape for DMT and ayahuasca trials expanded after 2020-2021, dominated by early-stage development with conservative eligibility criteria and a focus on acute safety and subjective effects, while disorder-specific programs beyond depression remain limited. |
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.
Comparable studies
Other systematic reviews and meta-analyses on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala alkaloids Humans (ritual ayahuasca use) | 2006 | Systematic review | |
| Ayahuasca, dimethyltryptamine, and psychosis: a systematic review of human studies | 2017 | Systematic review | |
| A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010. | 2012 | Systematic review | |
| United States National Institutes of Health grant funding for psychedelic-assisted therapy clinical trials from 2006-2020. | 2022 | Systematic review | |
| Effects of ayahuasca and its alkaloids on substance use disorders: an updated (2016-2020) systematic review of preclinical and human studies. Rodents and humans (healthy ritual ayahuasca users and patients with substance use... | 2022 | Systematic review | n = 9 |
Citations in the library
Cited by 2
- N,N-Dimethyltryptamine and harmine formulation alters transient EEG topography sequences near the peak of the psychedelic state Journal of Psychopharmacology September 22, 2026
- Direct anti-inflammatory actions of N,N -dimethyltryptamine on microglia are revealed by proteomic profiling and receptor pharmacology bioRxiv (Cold Spring Harbor Laboratory) August 11, 2026
Cites 47
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Dose-Response Study of N,N-Dimethyltryptamine in Humans Archives of General Psychiatry February 1, 1994
- Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca Journal of Ethnopharmacology April 1, 1984
- Recreational Use, Analysis and Toxicity of Tryptamines Current Neuropharmacology December 10, 2014
- Great Expectations: recommendations for improving the methodological rigor of psychedelic clinical trials Psychopharmacology April 1, 2022
and 42 more in the library