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, Laura Borghans, Johan G C Van Hasselt, J M A van Gerven, Gabriël E. Jacobs
Clinical Pharmacokinetics February 1, 2025 DOI: 10.1007/s40262-024-01450-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Humans |
| Intervention | DMT |
| Topics | DMT 5-MeO-DMT |
| Keywords | Psychedelics Pharmacology Mental health treatment |
| Citations | 7 |
| Key findings | DMT is rapidly eliminated with a half-life of 4.8–19.0 minutes and shows high intersubject variability in pharmacokinetics, but existing human studies are limited and lack detailed reporting. |
Abstract
N,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. Clinical 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. In 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. This 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 |
| 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 | |
| Clinical pharmacokinetics of N,N-dimethyltryptamine (DMT): a systematic review and post-hoc analysis Humans | 2025 | Systematic review | |
| Pharmacological, clinical, and translational evidence for N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and zalsupindole: a systematic review. | 2026 | Systematic review |
Citations in the library
Cited by 10
- Safety, Pharmacokinetics, and Pharmacodynamics of a 6-h N,N-Dimethyltryptamine (DMT) Infusion in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial. Clinical and Translational Science May 1, 2025
- Modification of natural tryptamines for the treatment of neuropsychiatric diseases Journal of Psychopharmacology October 4, 2025
- Population pharmacokinetic-pharmacodynamic modeling of co-administered N,N-dimethyltryptamine and harmine in healthy subjects. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie July 9, 2025
- Fatalities following DMT use: Two case reports and a review of the literature. Journal of Analytical Toxicology July 9, 2025
- Optimized Parenteral and Intranasal Formulations of Tryptamine Psychedelics for Rapid-Acting Antidepressant Therapy. ACS Medicinal Chemistry Letters June 12, 2025
and 5 more in the library
Cites 25
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Current Drug Abuse Reviews June 1, 2013
- Neural correlates of the DMT experience assessed with multivariate EEG. Scientific Reports November 19, 2019
- Towards an understanding of psychedelic-induced neuroplasticity. Neuropsychopharmacology 2023
and 20 more in the library