DMT: chemistry

DMT is an indole-containing molecule, described as the archetype for the serotonergic psychedelics as a class [1]. It is also reported to be one of the few psychedelic compounds naturally present in the human body, though its biological purpose there is unclear [2]. Its effects are tied to serotonin receptor activity: it's reported to act as an agonist at some serotonin receptor subtypes and an antagonist at others [3]. Older research described it instead as blocking serotonin's action in brain tissue outright, a claim that remains contested [4].

How DMT is taken changes both whether it takes effect and how quickly, depending on whether it is combined with an MAO inhibitor [5]. Some sources hold that DMT is inactive when taken by mouth alone, producing effects only when injected, sniffed, or smoked [4]. What changes that picture is monoamine oxidase (MAO): inhibiting MAO enzymes in the gut and liver is enough to stop DMT being broken down before it reaches systemic circulation, allowing oral DMT into the bloodstream and brain [5]. That's the chemistry behind ayahuasca, a tea combining DMT with MAO-inhibiting beta-carboline alkaloids [5]. DMT can also be produced synthetically [6].

Injected DMT reaches peak blood levels and peak psychological effects within about two minutes, and is largely resolved by half an hour [7][8]. Ayahuasca, relying on MAO inhibition to survive digestion, peaks between 1.5 and 2 hours after oral dosing instead [5].

References

1. Dark Classics in Chemical Neuroscience: N,N-Dimethyltryptamine (DMT) — ACS Chemical Neuroscience
2. DMT Therapy Information — UC Berkeley Center for the Science of Psychedelics
3. Dimethyltryptamine — DrugBank
4. DMT — Encyclopaedia Britannica
5. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics — Journal of Pharmacology and Experimental Therapeutics (ASPET)
6. N,N-Dimethyltryptamine (DMT) — U.S. Drug Enforcement Administration
7. Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects — Archives of General Psychiatry (JAMA Network)
8. Dose-response study of N,N-dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale — Archives of General Psychiatry (JAMA Network)