DMT: interactions

MAOIs and serotonin syndrome

Ayahuasca pairs DMT with plant-derived MAO-inhibiting beta-carboline alkaloids, inhibiting monoamine oxidase (MAO) in the gut and liver and preventing first-pass metabolism of DMT and giving it access to systemic circulation and the central nervous system [1]. Combining ayahuasca with SSRI antidepressants can produce serotonin syndrome, and outcomes have been described as potentially grave [2][3]. Signs to know, whether they show up in yourself or someone you're with: involuntary muscle jerking, wildly swinging vital signs, agitation shading into unresponsiveness, muscle rigidity, high fever, and seizures [4]. Get emergency care if these appear.

Any serotonergic medication needs to be screened for before combining with a psychedelic [5], and the interactions between classic psychedelics and antidepressants generally remain under-researched [3]. Serotonergic psychotropics that don't involve an MAOI are reported as lower risk when combined with psychedelics that also don't involve an MAOI [4] — but "lower" isn't "clear," and this applies to psychedelics as a class, not as a guarantee for DMT specifically.

Cardiovascular load

DMT raises blood pressure, heart rate, pupil diameter, and body temperature in a dose-dependent way [6]. With ayahuasca specifically, diastolic blood pressure rises significantly at higher doses [1], while systolic pressure and heart rate rise more moderately [1]. Co-ingestion with other substances and underlying health conditions are both factors reported to increase overall risk with psychedelics [5].

Unknown substances

As with psychedelics generally, samples submitted for testing occasionally contain adulterants such as methamphetamine or fentanyl, though this is reported as rare [7]. As with psychedelics generally, drug checking, where available, may help identify impurities in a sample [7].

References

1. Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics — Journal of Pharmacology and Experimental Therapeutics (ASPET)
2. Ayahuasca preparations and serotonin reuptake inhibitors: a potential combination for severe adverse interactions — Journal of Psychoactive Drugs (Taylor & Francis)
3. Drug–drug interactions involving classic psychedelics: A systematic review — Journal of Psychopharmacology
4. Serotonin toxicity of serotonergic psychedelics — PubMed
5. Pharmacological Properties of Psychedelics with a Special Focus on Potential Harms — PubMed
6. Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects — Archives of General Psychiatry (JAMA Network)
7. Harm reduction practises for users of psychedelic drugs: a scoping review — Harm Reduction Journal