Clinical pharmacokinetics of N,N-dimethyltryptamine (DMT): a systematic review and post-hoc analysis
Katelijne V. van der Heijden, Marije E. Otto, Jan W. Schoones, Michiel J. van Esdonk, L.g.j.m. Van Borghans, Johan G C Van Hasselt, J.M.A. Gerven, Gabriël E. Jacobs
Leiden Repository 2025 DOI: 10.1007/s40262-024-01450-8#citeas (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Humans |
| Topics | 5-MeO-DMT DMT |
| Keywords | Pharmacokinetics Bolus digestion Volume of distribution Dosing Intravenous bolus Pharmacology |
| Key findings | The pharmacokinetics of DMT in humans have been characterized to a limited extent, with high intersubject variability and differences in exposure following bolus versus prolonged infusion. |
Abstract
BACKGROUND AND OBJECTIVE\nMETHODS\nRESULTS\nCONCLUSION\nN,N-Dimethyltryptamine (DMT) is currently being studied for its therapeutic potential in various psychiatric disorders. An understanding of its pharmacokinetics (PK) is essential to determine appropriate dose ranges in future clinical studies. We conducted a systematic literature review on the PK of DMT.\nClinical studies that administered known amounts of DMT and reported PK data and/or parameters in humans were included. Additionally, raw PK data were requested from authors and/or extracted from publications.\nIn total, 219 references were retrieved, of which 13 publications were included, covering eight distinct datasets. All studies administered DMT intravenously in various infusion schemes, except for one intramuscular administration. High variability in dose-normalized exposure parameters and differences in exposure for bolus versus infusion administration were observed. DMT is extensively redistributed to other tissues, based on its biphasic elimination profile and high volume of distribution in the terminal elimination phase (range 123-1084 L). It is eliminated rapidly, with a half-life of 4.8-19.0 min and clearance of 8.1-46.8 L/min. This is a result of the rapid metabolization of DMT to indole-3-acetic acid (IAA), which is also reflected in the fact that the time of maximum concentration of IAA is similar to that of DMT.\nThis review demonstrates that the PK of DMT in humans have been characterized to a limited extent, and publications lack details with regards to demographics, absolute doses, and PK parameters. Additional studies are necessary to investigate high intersubject variability and differences in exposure following bolus or prolonged infusion. Addressing these issues is essential for the development of DMT as a pharmacotherapeutic in neuropsychiatry.
Comparable studies
Other systematic reviews and meta-analyses on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A critical review of reports of endogenous psychedelic N, N-dimethyltryptamines in humans: 1955-2010. | 2012 | Systematic review | |
| Short-term safety and tolerability profile of 5-methoxy-N,N-dimethyltryptamine in human subjects: a systematic review of clinical trials. Healthy volunteers and patients with treatment-resistant depression | 2024 | Systematic review | n = 78 |
| Clinical Pharmacokinetics of N,N-Dimethyltryptamine (DMT): A Systematic Review and Post-hoc Analysis. Humans | 2025 | Systematic review | |
| Efficacy of N, N-dimethyltryptamine (DMT) psychedelic therapy for substance misuse: A systematic review and meta-analysis Individuals with substance misuse | 2026 | Systematic review and meta-analysis | |
| Pharmacological, clinical, and translational evidence for N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and zalsupindole: a systematic review. | 2026 | Systematic review |