Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions.
Hong-Wu Shen, Xi-Ling Jiang, Jerrold C Winter, Ai-Ming Yu
Current Drug Metabolism October 1, 2010 DOI: 10.2174/138920010794233495 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Population | Humans (pharmacokinetics) |
| Topics | 5-MeO-DMT DMT |
| Keywords | Psychedelic Metabolism: 5-MEO-DMT Bufotenine Transform Metabolized Enzyme Metabolic pathways Active compound Natural psychedelic Drug interactions: combining Inhibitors Harmaline Amplified effects Increase exposure Brain chemistry Concerns |
| Citations | 171 |
| Key findings | Concurrent use of harmaline with 5-MeO-DMT reduces deamination metabolism, increasing exposure to both the parent drug and its active metabolite bufotenine, which may lead to serotonin toxicity. |
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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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State of the evidence: 5-MeO-DMT Opposes
Concurrent use of harmaline with 5-MeO-DMT reduces its deamination metabolism, increasing exposure to the parent drug and its active metabolite bufotenine and potentially producing hyperserotonergic effects or serotonin toxicity.
Synthesized
Comparable studies
Other narrative reviews on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neuropharmacology of N,N-dimethyltryptamine | 2016 | Review | |
| N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function Humans and animals (general) | 2018 | Review | |
| Dark Classics in Chemical Neuroscience:N,N-Dimethyltryptamine (DMT) | 2018 | Review | |
| A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity. | 2013 | Review | |
| Pharmepéna-Psychonautics: Human intranasal, sublingual and oral pharmacology of 5-methoxy-N,N-dimethyl-tryptamine. | 2001 | Review |
Citations in the library
Cited by 122
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Recreational Use, Analysis and Toxicity of Tryptamines Current Neuropharmacology December 10, 2014
- A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology April 13, 2019
- Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. PLoS One 2014
and 117 more in the library
Cites 47
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- Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. Pharmacology & Therapeutics May 1, 2004
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and 42 more in the library