MDMA interactions with pharmaceuticals and drugs of abuse

Expert Opin Drug Metab Toxicol. 2020 May;16(5):357-369. doi: 10.1080/17425255.2020.1749262. Epub 2020 Apr 12.


Introduction: MDMA (3,4-methylenedioxymethamphetamine), a synthetic ring-substituted amphetamine, has become one of the most widely used recreational psychostimulant drugs in the world. Among recreational ecstasy/MDMA users, polydrug use is a phenomenon whose common purpose is to experience the synergistic effect of the combined drugs, moderate MDMA effects, prevent potential toxicity, enhance a high or come down from a high from other drugs, or simply to treat existing medical conditions. Thus, MDMA-drug interactions (MDMA-DIs) lead to a higher risk of acute and life-threatening MDMA toxicity.Areas covered: This article provides an overview of the MDMA-DIs with pharmaceuticals and drugs of abuse. In addition, available evidence is summarized along with clinical recommendations. Finally, the increasing importance of MDMA-DIs is highlighted.Expert opinion: There is a reduced number of published MDMA-DIs studies and scarce clinically significant MDMA-DIs documented in the literature. Experimental evidence points out the relevance of MDMA-DI's when MDMA is co-administered with pharmaceuticals that are metabolized by the CYP2D6 due to MDMA inhibitory action and in the case of repeated MDMA administration (MDMA-MDMAIs).

Keywords: 3,4-methylenedioxymethamphetamine (MDMA); acute MDMA toxicity; drug interaction (DI); pharmacodynamics; pharmacokinetics; polydrug use.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytochrome P-450 CYP2D6 / metabolism
  • Drug Interactions
  • Drug Synergism
  • Hallucinogens / administration & dosage*
  • Hallucinogens / toxicity
  • Humans
  • Illicit Drugs / toxicity*
  • N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage*
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / metabolism
  • Substance-Related Disorders / epidemiology


  • Hallucinogens
  • Illicit Drugs
  • Pharmaceutical Preparations
  • Cytochrome P-450 CYP2D6
  • N-Methyl-3,4-methylenedioxyamphetamine