Psychedelic 5-methoxy-N,N-dimethyltryptamine: Metabolism, pharmacokinetics, drug interactions, and pharmacological actions

Hong Wu Shen, Xi Ling Jiang, Jerrold C. Winter, Aiming Yu

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. It acts as a nonselective serotonin (5-HT) agonist and causes many physiological and behavioral changes. 5-MeO-DMT is O-demethylated by polymorphic cytochrome P450 2D6 (CYP2D6) to an active metabolite, bufotenine, while it is mainly inactivated through the deamination pathway mediated by monoamine oxidase A (MAO-A). 5-MeO-DMT is often used with MAO-A inhibitors such as harmaline. Concurrent use of harmaline reduces 5-MeO-DMT deamination metabolism and leads to a prolonged and increased exposure to the parent drug 5-MeO-DMT, as well as the active metabolite bufotenine. Harmaline, 5-MeO-DMT and bufotenine act agonistically on serotonergic systems and may result in hyperserotonergic effects or serotonin toxicity. Interestingly, CYP2D6 also has important contribution to harmaline metabolism, and CYP2D6 genetic polymorphism may cause considerable variability in the metabolism, pharmacokinetics and dynamics of harmaline and its interaction with 5-MeO-DMT. Therefore, this review summarizes recent findings on biotransformation, pharmacokinetics, and pharmacological actions of 5-MeO-DMT. In addition, the pharmacokinetic and pharmacodynamic drug-drug interactions between harmaline and 5-MeO-DMT, potential involvement of CYP2D6 pharmacogenetics, and risks of 5-MeO-DMT intoxication are discussed.

Original languageEnglish (US)
Pages (from-to)659-666
Number of pages8
JournalCurrent Drug Metabolism
Volume11
Issue number8
DOIs
StatePublished - Oct 2010
Externally publishedYes

Keywords

  • 5-MeO-DMT
  • CYP2D6
  • Drug interaction
  • Harmaline
  • Metabolism
  • Pharmacogenetics
  • Pharmacokinetics
  • Serotonin toxicity

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Biochemistry

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