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

This review (2010) summarizes recent findings on biotransformation, pharmacokinetics, and pharmacological actions of 5-MeO-DMT, with particular regard to hyper-serotonergic effects of 5-MeO-DMT and bufotenine in response to inhibition of the monoamine oxidase (MAO) metabolic pathway via harmaline (together often found in ayahuasca brews).

Abstract of 5-MeO-DMT: metabolism, pharmacokinetics, drug interactions, and pharmacological actions

Review: 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.”

Authors: Hong-Wu Shen, Xi-Ling Jiang, Jerrold C. Winter & Ai-Ming Yu

Summary of 5-MeO-DMT: metabolism, pharmacokinetics, drug interactions, and pharmacological actions

Indolealkylamine drugs include many antimigraine triptans and psychedelic substances of abuse, such as 5-MeO-DMT, which is an endogenous psychotoxin and may be associated with psychotic disorders such as schizophrenic psychosis.

5-MeO-DMT is a potent, fast-acting hallucinogen that produces psychedelic effects in human subjects. It was not a federally controlled substance in the United States until August 2009 when the Drug Enforcement Administration issued a notice intending to place 5-MeO-DMT into Schedule I of the Controlled Substances Act.

5-MeO-DMT is inactivated through a deamination pathway mediated by monoamine oxidase A (MAO-A), and is O-demethylated by cytochrome P450 2D6 (CYP2D6) enzyme to produce an active metabolite, bufotenine. Concurrent use of 5-MeO-DMT with an MAO inhibitor may cause more severe toxicity.

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

https://doi.org/10.2174/138920010794233495

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Cite this paper (APA)

Shen, H. W., Jiang, X. L., C Winter, J., & Yu, A. M. (2010). Psychedelic 5-methoxy-N, N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Current drug metabolism11(8), 659-666.

Study details

Compounds studied
5-MeO-DMT

Topics studied
Chemistry Neuroscience

Study characteristics
Literature Review

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