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Metabolism and urinary disposition of N,N‐dimethyltryptamine after oral and smoked administration: a comparative study

Jordi Riba, Ethan H. Mcilhenny, José Carlos Bouso, Steven A. Barker

Drug Testing and Analysis July 28, 2014 DOI: 10.1002/dta.1685 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 6
Population DMT users
Intervention DMT
Dose 25 mg
Topics 5-MeO-DMT DMT
Keywords Oral administration Urine Ingestion Pharmacology Metabolite Alkaloid Metabolism Pharmacokinetics Hallucinogen
Citations 96
Key findings Oral DMT is completely metabolized by MAO to indole-3-acetic acid and produces no psychoactive effects, whereas smoked DMT shifts metabolism to CYP-dependent pathways, yielding unmetabolized DMT and psychoactivity.

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.

Comparable studies

Other observational and cohort studies on DMT, most cited first.

Study Year Design Participants
Neural correlates of the DMT experience assessed with multivariate EEG. 6 female, 7 male human participants 2019 Observational cohort n = 13
A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Volunteers who inhaled vapor from dried toad secretion at several European locations 2019 Observational cohort n = 42
Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study Individuals at a psychospiritual retreat in Mexico 2018 Observational cohort n = 20
Neural and subjective effects of inhaled N,N-dimethyltryptamine in natural settings. Healthy and experienced participants 2021 Observational field study n = 35
A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N, N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers. Healthy volunteers 2021 Prospective dose-finding study n = 22

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