Clinical Pharmacokinetics of N,N-Dimethyltryptamine (DMT): A Systematic Review and Post-hoc Analysis.

A systematic review of 13 publications covering eight datasets found that the pharmacokinetics of DMT in humans have been characterized only to a limited extent. All studies administered DMT intravenously except one intramuscular injection. DMT is rapidly metabolized to indole-3-acetic acid (IAA), with a half-life of 4.8–19.0 minutes and clearance of 8.1–46.8 L/min. It shows extensive tissue redistribution, indicated by a high terminal volume of distribution (123–1084 L). High variability in dose-normalized exposure and differences between bolus and infusion administration were observed. Publications often lack details on demographics, absolute doses, and pharmacokinetic parameters, highlighting the need for further studies.

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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.