Metabolism and disposition of N,N‐dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca
Jordi Riba, Ethan H. Mcilhenny, Marta Valle, José Carlos Bouso, Steven A. Barker
Drug Testing and Analysis April 19, 2012 DOI: 10.1002/dta.1344 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational pharmacokinetic study Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Healthy male volunteers |
| Dose | 1.0 mg DMT/kg body weight |
| Duration | 24-hour urine collection |
| Topics | Ayahuasca 5-MeO-DMT DMT |
| Keywords | Harmine Harmaline Alkaloid Pharmacology Oxidative deamination Metabolite Hallucinogen Peganum harmala Oral administration Urine Ingestion |
| Citations | 91 |
| Key findings | In humans, less than 1% of oral DMT is excreted unchanged, with alternative metabolic routes beyond monoamine-oxidase accounting for about 68% recovery, while harmala alkaloid recoveries vary widely (9–65%) via O-demethylation and conjugation. |
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. Copyright © 2012 John Wiley & Sons, Ltd.
Comparable studies
Other experimental studies on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Short term changes in the proteome of human cerebral organoids induced by 5-MeO-DMT. Human cerebral organoids | 2017 | Experimental study | |
| Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment Volunteers | 2019 | Within-subjects experimental study | n = 11 |
| Unmasking of a neonatal somatovesical reflex in adult cats by the serotonin autoreceptor agonist 5-methoxy-N,N-dimethyltryptamine. Adult cats | 1990 | Experimental study | n = 10 |
| Studies on the Mechanism of Action of Monoamine Oxidase: Metabolism of N,N-Dimethyltryptamine and N,N-Dimethyltryptamine-N-Oxide | 1962 | Experimental study | |
| The excitability and rhythm of medullary respiratory neurons in the cat are altered by the serotonin receptor agonist 5-methoxy-N,N, dimethyltryptamine. Cats | 1994 | Experimental study |
Citations in the library
Cited by 68
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- Neuropharmacology of N,N-dimethyltryptamine Brain Research Bulletin April 30, 2016
- Ayahuasca: Psychological and Physiologic Effects, Pharmacology and Potential Uses in Addiction and Mental Illness Current Neuropharmacology March 2, 2018
- N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function Frontiers in Neuroscience August 6, 2018
- The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro Scientific Reports July 7, 2017
and 63 more in the library
Cites 17
- Dose-Response Study of N,N-Dimethyltryptamine in Humans Archives of General Psychiatry February 1, 1994
- Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca Journal of Ethnopharmacology April 1, 1984
- Human Pharmacology of Ayahuasca: Subjective and Cardiovascular Effects, Monoamine Metabolite Excretion, and Pharmacokinetics Journal of Pharmacology and Experimental Therapeutics June 18, 2003
- Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers Psychopharmacology February 22, 2001
- Psychedelics and the Human Receptorome PLoS One 2010
and 12 more in the library