Grant: Project Grant

MDMA (3,4-methylenedioxy-methamphetamine) is a controlled substance widely used as a recreational drug (Ecstasy/Molly). In Canada, 4% of youths aged 14-24 report having used ecstasy during the previous 12 months. MDMA is generally used for its mood enhancing properties. Desired short-term effects include feelings of euphoria, pro-social/empathy and increased energy. However an occasional dangerous adverse effect of MDMA is hyponatremia (low blood sodium levels), which is a causal factor in hospitalized patients experiencing headaches, dizziness or seizures following MDMA ingestion. A 5-year study by the California Poison Control System has shown that the incidence of MDMA-induced hyponatremia is significantly (4X) greater in women than men and is associated with a death rate of ~5%. Despite MDMA's status as a controlled substance, MDMA is being promoted to assist psychotherapy treatment for various conditions, including post-traumatic stress disorder, social anxiety and autism spectrum disorder. While potentially useful, this incentive to use MDMA in the clinical setting is happening in the relative absence of mechanistic studies investigating the drug's potential toxic side effects and could ultimately enhance use by recreational users. Therefore, in this project we propose to define the mechanisms by which MDMA induces hyponatremia in a rat model that closely replicates the human condition, and to define the basis for its greater impact in females.