MDMA interactions with pharmaceuticals and drugs of abuse

ABSTRACT

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

Article highlights

• The knowledge of potential MDMA-DIs is crucial to minimize acute potential MDMA toxicity.

• Polydrug use in recreational ecstasy/MDMA users, including pharmaceuticals and drugs of abuse, is an added risk factor that can lead to MDMA-DIs and it represents an important source of related medical emergencies and even fatalities.

• Most relevant documented MDMA-DIs from experimental evidence show a pharmacokinetic interaction mediated by CYP2D6 with antidepressants with CYP2D6 inhibitory action.

• Most clinically relevant MDMA-DIs are consistent with mechanism-based inhibition of CYP2D6 by coadministration of CYP2D6 inhibitors (including pharmaceuticals and MDMA).

• Repeated use of MDMA (MDMA-MDMAIs) is a relevant MDMA-DI which should be considered in order to minimize potential acute toxicity.

• MDMA-DIs are a complicated clinical entity that involve, in addition to the very interaction factors, other determinants to be considered (sex-gender, race-ethnicity, genetic polymorphism …), which makes them unpredictable.

• The lack of scientific knowledge concerning MDMA-DIs with the most used pharmaceuticals and drugs of abuse is highlighted.

• This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported in part by grants from Instituto de Salud Carlos III (ISCIII, FIS-FEDER, FIS-PI17/01962), the ISCIII-Red de TrastornosAdictivos (RTA RD16/0017/003 and RD16/0017/0010), and Suport Grups de Recerca AGAUR-Gencat (2017 SGR 316 and 2017 SGR 530). Esther Papaseit is a Juan Rodés fellowship (ISC-III, JR16/00020).