Cardiovascular and neuroendocrine effects and pharmacokinetics of 3,4-methylenedioxymethamphetamine in humans

The cardiovascular and neuroendocrine effects and pharmacokinetics of 3,4-m ethylenedioxymethamphetamine (MDMA, "ecstasy") were assessed in a double-bl ind, randomized, crossover, and controlled (placebo and amphetamine) clinic al trial. Eight men with experience in the recreational use of MDMA partici pated in four 10-h experimental sessions with a 1-week washout period. Sing le oral doses of 125 mg and 75 mg of MDMA, 40 mg of amphetamine, and placeb o were given. Both MDMA doses significantly increased blood pressure (incre ases of 40 mm Hg in systolic blood pressure), heart rate (increases of 30 b eats/min), and pupillary diameter (mydriasis) as compared with placebo. Ora l temperature did not show significant changes in any drug-active condition . Plasma cortisol levels showed a statistically significant increase after MDMA administration. Prolactin levels only increased after high dose of MDM A. C-max values for 125-mg and 75-mg MDMA doses were 236.4 and 130.9 ng/ml, and T-max was observed at 2.4 and 1.8 h, respectively. Elimination half-li fe was 8.6 h and 7.7 h for high and low MDMA doses, respectively. Amphetami ne half-life was 15 h. Between 8 and 9% of the doses of MDMA appeared in pl asma in the form of 3,4-methylenedioxyamphetamine. The important cardiovasc ular effects observed after MDMA administration in laboratory conditions at rest (increases of 40 mm Hg in systolic blood pressure and 30 beats/min in pulse rate) could be relevant in terms of toxicity in real-life conditions (e.g., crowded places and physical activity).