**6.2 MDMA (3,4-methylenedioxymethamphetamine) and hyponatremia**

Stimulant use disorder in DSM-5 [1] is defined as a pattern of stimulant use within the past 12 months that has led to significant impairment in one's life characterized by at least two of the following including the stimulant is taken in larger amounts, persistent desire to cut down, increased time obtaining the stimulant, cravings, continued use despite recurrent impairment in social functioning, developed tolerance, and withdrawal symptoms present when stimulant use is ceased. MDMA (3,4-methylenedioxymethamphetamine), a stimulant, is thought to be associated with hyponatremia because of increased diaphoresis, yielding sodium loss, and compensatory water intoxication. It is not a common side effect of MDMA use; however, Armitage et al. [19] presented a case report of an 18-year-old woman who had a generalized tonic-clonic seizure in the setting of hyponatremia from MDMA intoxication. This woman's serum sodium was 121, notably close to what many would argue is severe hyponatremia. Notably, MDMA related hyponatremia with seizure is more common among young women under 30 years of age, particularly because of estrogen inhibiting the Na+-K+-ATPase. This ultimately inhibits

a known compensatory mechanism for cerebral edema, which may place young women at increased risk of neurological impacts of hyponatremia with MDMA use. Further, a metabolite of MDMA, 4-hydroxy-3-methoxymethamphetamine (HMMA), is documented to stimulate ADH release, which can worsen hyponatremia. These are vital considerations given the potential sequela of seizure, and the urgency of its management.
