Ecstasy (3,4-methylenedioxymethamphetamine): Cardiovascular effects and mechanisms

3,4-methylenedioxymethamphetamine or MDMA (known as "ecstasy") is a recreational drug of abuse, popular worldwide for its distinctive psychotropic effects. Currently, the therapeutic potential of MDMA in psychotherapy has attracted a lot of interest from the scientific community, despite the multitude of effects that this drug of abuse elicits on the human body. While neuronal effects have been the most studied, cardiovascular effects have also been described, as increased blood pressure and heart rate are the most recognizable. However, other effects have also been described at the cardiac (impaired cardiac contractile function, arrhythmias, myocardial necrosis and valvular heart disease) and vascular (vasoconstriction, disruption of vascular integrity and altered haemostasis) levels. Several mechanisms have been proposed, from the interaction with monoamine transporters and receptors to the promotion of oxidative stress or the activation of matrix metalloproteinases (MMPs). This review provides an overview of the cardiovascular implications of MDMA intake and underlying mechanisms, relevant when considering its consumption as drug of abuse but also when considering its therapeutic potential in psychiatry. Moreover, the risk/benefit ratio of the therapeutic use of MDMA remains to be fully elucidated from a cardiovascular standpoint, particularly in patients with underlying cardiovascular disease.