MDMA and its metabolites can stimulate release of the hormones vasopressin and oxytocin from rat hypothalamic tissue in the laboratory. The metabolite HMMA (4-hydroxy-3-methoxymethamphetamine) was the most potent, increasing basal vasopressin release more than twofold and oxytocin release by about 60% at a concentration of 10 nM. MDMA itself produced smaller increases. The effect on vasopressin release was consistently greater than on oxytocin. These findings suggest that MDMA-induced hyponatraemia (low blood sodium) may result from excessive vasopressin secretion triggered by the drug or its breakdown products.
MDMA (ecstasy) can cause dangerously low sodium levels by triggering inappropriate secretion of the antidiuretic hormone arginine vasopressin (AVP). In eight healthy men given a low 40 mg dose of MDMA, plasma AVP rose significantly at 1, 2, and 4 hours. A negative correlation between MDMA and AVP at 1 hour suggested a metabolite might drive the increase. Testing MDMA and five of its metabolites on isolated rat hypothalamus tissue showed all compounds increased AVP release, with the major metabolite HMMA being the most potent and DHMA the least. Most compounds also enhanced AVP release in response to potassium stimulation. These in vitro results confirm that MDMA metabolites, not just the parent drug, contribute to AVP secretion.