Metabolism and urinary disposition of N,N‐dimethyltryptamine after oral and smoked administration: a comparative study
Drug Testing and Analysis – July 28, 2014
Source: OpenAlex
Summary
Oral administration of N, N-dimethyltryptamine (DMT) results in no psychoactive effects due to extensive degradation by monoamine oxidase (MAO). In a study involving 6 DMT users, after ingesting 25 mg orally, urine analysis revealed 97% of metabolites were indole-3-acetic acid (IAA), with no DMT detected. Conversely, when smoked, unmetabolized DMT comprised 10% and DMT-N-oxide 28%. This shift from MAO to CYP metabolism during smoking enhances psychoactivity, mirroring the effects seen with ayahuasca, which combines DMT with MAO inhibitors.
Abstract
N , N ‐dimethyltryptamine (DMT) is a widely distributed plant alkaloid that displays partial agonist activity at the 5‐HT 2A receptor and induces intense psychedelic effects in humans when administered parenterally. However, self‐administration studies have reported a total lack of activity following oral intake. This is thought to be due to extensive degradation by monoamine oxidase (MAO). Despite increased use of DMT and DMT‐containing preparations, such as the plant tea ayahuasca, the biotransformation of DMT in humans when administered alone is relatively unknown. Here we used high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry (MS/MS) to characterize the metabolism and disposition of oral and smoked DMT. Twenty‐four‐hour urine samples were obtained from 6 DMT users before and after intake of 25 mg DMT doses on two separate sessions. In one session, DMT was taken orally and in another it was smoked. After oral ingestion, no psychotropic effects were experienced and no DMT was recovered in urine. MAO‐dependent indole‐3‐acetic acid (IAA) represented 97% of the recovered compounds, whereas DMT‐ N ‐oxide (DMT‐NO) accounted for only 3%. When the smoked route was used, the drug was fully psychoactive, unmetabolized DMT and DMT‐NO rose to 10% and 28%, respectively, and IAA levels dropped to 63%. An inverse correlation was found between the IAA/DMT‐NO ratio and subjective effects scores. These findings show that in the smoked route a shift from the highly efficient MAO‐dependent to the less efficient CYP‐dependent metabolism takes place. This shift leads to psychoactivity and is analogous to that observed in ayahuasca preparations combining DMT with MAO inhibitors. Copyright © 2014 John Wiley & Sons, Ltd.