title: Metabolism and disposition of N,N-dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca.
abstract: Ayahuasca is an Amazonian psychotropic plant tea obtained from Banisteriopsis caapi, which contains β-carboline alkaloids, chiefly harmine, harmaline and tetrahydroharmine. The tea usually incorporates the leaves of Psychotria viridis or Diplopterys cabrerana, which are rich in N,N-dimethyltryptamine (DMT), a psychedelic 5-HT(2A/1A/2C) agonist. The β-carbolines reversibly inhibit monoamine-oxidase (MAO), effectively preventing oxidative deamination of the orally labile DMT and allowing its absorption and access to the central nervous system. Despite increased use of the tea worldwide, the metabolism and excretion of DMT and the β-carbolines has not been studied systematically in humans following ingestion of ayahuasca. In the present work, we used an analytical method involving high performance liquid chromatography (HPLC)/electrospray ionization (ESI)/selected reaction monitoring (SRM)/tandem mass spectrometry(MS/MS) to characterize the metabolism and disposition of ayahuasca alkaloids in humans. Twenty-four-hour urine samples were obtained from 10 healthy male volunteers following administration of an oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight). Results showed that less than 1% of the administered DMT dose was excreted unchanged. Around 50% was recovered as indole-3-acetic acid but also as DMT-N-oxide (10%) and other MAO-independent compounds. Recovery of DMT plus metabolites reached 68%. Harmol, harmalol, and tetrahydroharmol conjugates were abundant in urine. However, recoveries of each harmala alkaloid plus its O-demethylated metabolite varied greatly between 9 and 65%. The present results show the existence in humans of alternative metabolic routes for DMT other than biotransformation by MAO. Also that O-demethylation plus conjugation is an important but probably not the only metabolic route for the harmala alkaloids in humans.
authors.affiliation: Human Experimental Neuropsychopharmacology, Institute for Biomedical Research IIB Sant Pau, Barcelona, Spain. jriba@santpau.cat
authors.forename: Jordi
authors.initials: J
authors.lastname: Riba
authors.forename: Ethan H
authors.initials: EH
authors.lastname: McIlhenny
authors.forename: Marta
authors.initials: M
authors.lastname: Valle
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Bouso
authors.forename: Steven A
authors.initials: SA
authors.lastname: Barker
mesh_terms: D000328:Adult; D031581:Banisteriopsis / Q000737:chemistry*; D001628:Beverages / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D006213:Hallucinogens / Q000378:metabolism / Q000652:urine; D006246:Harmaline / Q000378:metabolism* / Q000652:urine; D006247:Harmine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D006801:Humans; D008297:Male; D004130:N,N-Dimethyltryptamine / Q000378:metabolism* / Q000652:urine; D032069:Psychotria / Q000737:chemistry; D017366:Serotonin Receptor Agonists / Q000378:metabolism* / Q000652:urine; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D006213:Hallucinogens; D017366:Serotonin Receptor Agonists; D006247:Harmine; D006246:Harmaline; D004130:N,N-Dimethyltryptamine