Clinical pharmacokinetics of N,N-dimethyltryptamine (DMT): a systematic review and post-hoc analysis

DMT (N,N-Dimethyltryptamine) is being studied for psychiatric disorders, but its pharmacokinetics (PK) are not fully characterized. This systematic review of 13 publications (eight datasets) found that most studies gave DMT intravenously, with one intramuscular dose. DMT shows high variability in dose-normalized exposure and differences between bolus and infusion administration. It is rapidly redistributed to tissues (volume of distribution 123-1084 L) and quickly eliminated (half-life 4.8-19.0 min, clearance 8.1-46.8 L/min), mainly by metabolization to indole-3-acetic acid. The review concludes that more studies are needed to understand intersubject variability and exposure differences, which are crucial for developing DMT as a therapy.

Study at a glance

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.