NutriStack
MDMA and Paroxetine, contraindicated.
Paroxetine blocks the serotonin transporter MDMA uses to release serotonin, and paroxetine is also a potent CYP2D6 inhibitor — the enzyme that clears MDMA. The combination both blunts MDMA's effect and raises MDMA blood levels, increasing the risk of serotonin syndrome, hyperthermia, and death.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- MDMA and Paroxetine
- Pair type
- Contraindicated
- Evidence (highest tier)
- Moderate
- Source citations
- 2 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. Paroxetine blocks the serotonin transporter MDMA uses to release serotonin, and paroxetine is also a potent CYP2D6 inhibitor — the enzyme that clears MDMA. The combination both blunts MDMA's effect and raises MDMA blood levels, increasing the risk of serotonin syndrome, hyperthermia, and death.
Mechanism. Paroxetine blocks SERT (preventing MDMA-induced serotonin release) and strongly inhibits CYP2D6 (impairing MDMA clearance). Net result: higher MDMA levels with disrupted serotonergic clearance.
Recommendation. Do not combine MDMA with paroxetine. If paroxetine is stopped, wait at least 1-2 weeks before any MDMA use.
Sources (2)
- Dobry Y, Rice T, Sher L. Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors. Int J Adolesc Med Health. 2013;25(3):193-9. PMID 24006318
- 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
Stack Score
How this pair moves the number.
Effect on the composite score
If both MDMA and Paroxetine 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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