Interaction databaseSupplement × PrescriptionReviewed May 2026

MDMA and Rizatriptan, contraindicated.

MDMA causes large serotonin release and can trigger severe serotonin toxicity and hyperthermia. Rizatriptan is a serotonin receptor agonist, so taking it around MDMA exposure adds avoidable serotonergic activity during an already high-risk state. Risk is higher with overheating, dehydration, stimulants, antidepressants, or repeated triptan dosing.

One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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At a glance

Substances
MDMA and Rizatriptan
Pair type
Contraindicated
Evidence (highest tier)
Moderate
Source citations
3 sources
Stack Score effect
−25 to your Stack Score (per scored contraindication row).
Scope
Supplement × Prescription
Last verified
May 30, 2026

Contraindicated · Moderate evidence

Contraindicated

What is happening. MDMA causes large serotonin release and can trigger severe serotonin toxicity and hyperthermia. Rizatriptan is a serotonin receptor agonist, so taking it around MDMA exposure adds avoidable serotonergic activity during an already high-risk state. Risk is higher with overheating, dehydration, stimulants, antidepressants, or repeated triptan dosing.

Mechanism. MDMA reverses serotonin transporter function and drives marked serotonin release. Rizatriptan activates 5-HT1B/1D receptors; combined serotonergic stress can worsen receptor overstimulation and make early toxicity harder to recognize.

Recommendation. Do not combine MDMA with rizatriptan. If MDMA was used, avoid taking rizatriptan and seek medical advice for severe headache, chest pain, high fever, confusion, muscle rigidity, or repeated vomiting. Treat fever, agitation, clonus, or confusion after overlap as an emergency.

Sources (3)
  1. Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). Pharmacol Rev. 2003;55(3):463-508. PMID 12869661
  2. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120. PMID 15784664
  3. Evans RW. The FDA alert on serotonin syndrome with combined use of SSRIs or SNRIs and triptans: an analysis of the 29 case reports. MedGenMed. 2007;9(3):48. PMID 18092054

Stack Score

How this pair moves the number.

Effect on the composite score

If both MDMA and Rizatriptan are in the same stack, this pair applies −25 to your Stack Score (per scored contraindication row).

The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.

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