MDMA

Hypertension, coronary artery disease, arrhythmias, and structural heart disease constitute absolute contraindications. MDMA's sympathomimetic effects produce clinically significant cardiovascular stress.

Epilepsy or conditions with lowered seizure threshold represent relative contraindications. MDMA and its complication serotonin syndrome both reduce seizure threshold.

Schizophrenia, schizoaffective disorder, and other psychotic spectrum conditions represent relative contraindications due to theoretical risk of psychotic exacerbation from 5-HT2A activation and dopamine release. Safety data absent.

MDMA-induced hepatotoxicity can occur dose-independently even in healthy individuals. Cases of fulminant hepatic failure requiring transplantation reported. Pre-existing liver disease substantially increases risk.

Use during pregnancy or breastfeeding is contraindicated due to absence of any human safety data and potent pharmacological effects that could affect fetal development.

MDMA is contraindicated in pregnancy due to absence of safety data and theoretical risks from sympathomimetic, hyperthermic, and serotonergic effects on fetal development.

Concurrent dextromethorphan use is contraindicated due to risk of fatal serotonin syndrome.

Combination of MDMA with any monoamine oxidase inhibitor (irreversible or reversible) is potentially lethal. Fatalities documented. Requires 14-day washout for irreversible MAOIs, 2-3 days for reversible MAOIs.

Concurrent serotonergic medication (SSRIs, SNRIs, TCAs, triptans, St. John's wort) is contraindicated without supervised taper. Phase 3 trial participants underwent psychiatric medication washout. Interaction is bidirectional: SSRIs reduce MDMA efficacy while MDMA + serotonergic drugs risk serotonin syndrome.

Any monoamine oxidase inhibitor — including irreversible (phenelzine, tranylcypromine), reversible (moclobemide), and selective MAO-B (selegiline at high doses) — must be discontinued with appropriate washout before MDMA exposure. Fatalities documented.

Concurrent tramadol use is contraindicated due to risk of fatal serotonin syndrome.