DMT

uncontrolled hypertension, unstable angina, recent myocardial infarction, severe heart failure

Transient cardiovascular activation is well-documented in healthy volunteers but has not been studied in cardiovascular disease populations. The relative contraindication reflects the theoretical risk that even transient sympathomimetic stress could be clinically significant in vulnerable individuals.

The seizure risk is based on class pharmacology (5-HT2A agonism) and is particularly concerning in combination with lithium. Case reports of seizures exist for LSD + lithium; no DMT-specific case data have been published.

No DMT-specific clinical data on bipolar patients exist. The absolute contraindication is based on the well-established risk of 5-HT2A agonists precipitating mania in bipolar I disorder, supported by clinical experience with LSD, psilocybin, and other serotonergic psychedelics.

Standard exclusion criterion in all psychedelic clinical trials. The risk is based on the pharmacological mechanism of 5-HT2A agonism and clinical experience across the serotonergic psychedelic class.

No human or animal reproductive toxicity studies have been published for DMT. The absolute contraindication is precautionary.

This is the most dangerous DMT-related drug interaction. PBPK modeling confirms clinically significant increases in DMT exposure with CYP2D6-inhibiting SSRIs (fluoxetine, paroxetine) when combined with ayahuasca. The interaction is both pharmacokinetic (increased DMT plasma levels) and pharmacodynamic (serotonin syndrome). This contraindication applies specifically to the ayahuasca/oral MAOI route, not to isolated smoked/IV DMT.