Midomafetamine (MDMA) interactions
Review the current reference classification for Midomafetamine (MDMA) paired with medications or other agents represented in the Arcametric reference library.
Reference information only. This resource summarizes information from external sources and isn't individualized medical advice or a determination of treatment suitability.
Interactors with a reference entry
Cardiovascular
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Midomafetamine (MDMA) and Propranolol Clinician Review
Beta blockade (demonstrated with pindolol) prevents MDMA-induced tachycardia but fails to prevent BP elevation. MDMA is a potent mechanism-based CYP2D6 inhibitor; propranolol is a CYP2D6 substrate — plausible increase in propranolol exposure raises bradycardia and hypotension risk during recovery.
Evidence: Hysek 2010 pindolol-MDMA trial; Yubero-Lahoz 2011 CYP2D6; Inderal label
GLP-1/GIP Agonist
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Midomafetamine (MDMA) and Zepbound (tirzepatide) Clinician Review
Delayed oral absorption may encourage premature redosing. Zepbound-related nausea/dehydration and AKI warning adds to physiologic strain in an already cardiovascularly demanding session.
Evidence: FDA label (Zepbound 2025) + mechanistic
MAOI
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Midomafetamine (MDMA) and Phenelzine (Nardil) Absolute Contraindication
CONTRAINDICATED. MDMA + MAOI is a documented cause of fatalities due to hyperthermia and serotonin syndrome.
Evidence: Vuori E et al. J Anal Toxicol. 2003; Multiple fatality reports.
Opioid
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Midomafetamine (MDMA) and Tramadol (Ultram) Absolute Contraindication
Severe serotonin syndrome and seizure risk. Tramadol is uniquely dangerous among opioids due to its SNRI properties.
Evidence: Case report, Mechanistic
Other Psychiatric
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Midomafetamine (MDMA) and Bupropion (Wellbutrin) Strong Caution
Exponential increase in MDMA plasma levels and seizure risk from strong CYP2D6 inhibition.
Evidence: Pharmacokinetic data
Serotonergic
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Midomafetamine (MDMA) and Dextromethorphan (DXM) Absolute Contraindication
Severe to fatal serotonin toxicity from dual 5-HT reuptake inhibition and releasing agent action.
Evidence: Case report, Mechanistic
SSRI/SNRI
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Midomafetamine (MDMA) and Fluoxetine (Prozac) Strong Caution
SSRIs block MDMA's primary mechanism (serotonin release via SERT). Effects severely blunted. Serotonin syndrome risk remains.
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Midomafetamine (MDMA) and Pristiq (desvenlafaxine) Strong Caution
Controlled human trial (duloxetine SNRI) shows SNRI class inhibits MDMA subjective effects while increasing plasma MDMA levels — blunting does not indicate safety. Pristiq carries label-grade serotonin syndrome and BP warnings.
Evidence: Hysek 2012 duloxetine-MDMA clinical trial + FDA label (Pristiq 2017)
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Midomafetamine (MDMA) and Venlafaxine (Effexor) Strong Caution
High risk of cardiovascular and serotonergic overload from competitive CYP2D6 inhibition and massive 5-HT release.
Evidence: Clinical trial, Case report
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