title: Metabolism and urinary disposition of N,N-dimethyltryptamine after oral and smoked administration: a comparative study.
abstract: 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. 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.
authors: Human Neuropsychopharmacology Group, Sant Pau Institute for Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, 167, Barcelona, 08025, Spain.|Centre d'Investigació de Medicaments, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Sant Antoni María Claret, 167, Barcelona, 08025, Spain.|Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain.
authors: Jordi
authors: J
authors: Riba
authors: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA.
authors: Ethan H
authors: EH
authors: McIlhenny
authors: Human Neuropsychopharmacology Group, Sant Pau Institute for Biomedical Research (IIB-Sant Pau), Sant Antoni María Claret, 167, Barcelona, 08025, Spain.|ICEERS - International Center for Ethnobotanical Education Research & Service, The Netherlands.
authors: José Carlos
authors: JC
authors: Bouso
authors: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, 70803, USA.
authors: Steven A
authors: SA
authors: Barker
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D006213:Hallucinogens / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D007210:Indoleacetic Acids / Q000032:analysis / Q000652:urine; D004130:N,N-Dimethyltryptamine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine*; D010087:Oxides / Q000032:analysis / Q000652:urine; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: D006213:Hallucinogens; D007210:Indoleacetic Acids; D010087:Oxides; C030737:indoleacetic acid; D004130:N,N-Dimethyltryptamine
keywords: DMT; human; metabolism; urinary excretion