Metabolism and urinary disposition of N,N-dimethyltryptamine (DMT) after oral and smoked administration: a comparative study
Authors:
Jordi Riba, Ethan H. McIlhenny, José Carlos Bouso, and Steven A. Barker.
Journal:
Drug Testing and Analysis
Year:
2014
About the study
This study compares the metabolism and disposition of N,N-dimethyltryptamine in a sample of experienced recreational users. Urine samples were obtained after intake via two different administration routes: oral ingestion, and smoked intake.
The samples were collected from six recreational users (three male and three female) who agreed to provide urine samples following both the intake of oral and smoked DMT doses. They self-administered doses of 30 mg of this substance, which was obtained by extraction from the root bark of Mimosa tenuiflora.
The results show that in the smoked route there is a shift from MAO-dependent to CYP-dependent metabolism. This shift is responsible for psychoactivity and is analogous to that observed in ayahuasca preparations.
Abstract
Rationale: N,N-dimethyltryptamine (DMT) is a widely distributed plant alkaloid that displays partial agonist activity at the 5-HT2A 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Photo by Ruvim Noga on Unsplash.
Categories:
Studies & papers
, Psychedelics
Tags:
DMT
, psychoactive
, psychedelics
, hallucinogens
, metabolism
, urinary excretion
, human
, scientific research
, study