Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans.
M. Mas, M. Farré, R. de la Torre, P. Roset, J. Ortuño, J. Segura, J. Camí
Journal of Pharmacology and Experimental Therapeutics July 1, 1999 Peer reviewed DOI: 10.1016/s0022-3565(24)34877-3 via Semantic Scholar 362 citations
Summary
In a double-blind, randomized, crossover trial, eight men with prior recreational MDMA use received single oral doses of 125 mg or 75 mg of MDMA, 40 mg of amphetamine, or placebo. Both MDMA doses significantly raised systolic blood pressure by 40 mm Hg and heart rate by 30 beats/min, and dilated pupils, compared with placebo. Oral temperature did not change significantly. Plasma cortisol increased after MDMA; prolactin only rose after the higher dose. MDMA elimination half-lives were 8.6 hours (high dose) and 7.7 hours (low dose). The cardiovascular effects at rest suggest potential toxicity in real-world settings with crowding or physical exertion.
Study at a glance
| Design | randomized controlled trial |
|---|---|
| Sample size | 8 |
| Population | men with experience in recreational use of MDMA |
| Key finding | Both 125 mg and 75 mg of MDMA significantly increased systolic blood pressure by 40 mm Hg and heart rate by 30 beats/min compared with placebo. |
Abstract
The cardiovascular and neuroendocrine effects and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") were assessed in a double-blind, randomized, crossover, and controlled (placebo and amphetamine) clinical trial. Eight men with experience in the recreational use of MDMA participated in four 10-h experimental sessions with a 1-week washout period. Single oral doses of 125 mg and 75 mg of MDMA, 40 mg of amphetamine, and placebo were given. Both MDMA doses significantly increased blood pressure (increases of 40 mm Hg in systolic blood pressure), heart rate (increases of 30 beats/min), and pupillary diameter (mydriasis) as compared with placebo. Oral 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 MDMA. Cmax values for 125-mg and 75-mg MDMA doses were 236.4 and 130.9 ng/ml, and Tmax was observed at 2.4 and 1.8 h, respectively. Elimination half-life was 8.6 h and 7.7 h for high and low MDMA doses, respectively. Amphetamine half-life was 15 h. Between 8 and 9% of the doses of MDMA appeared in plasma in the form of 3,4-methylenedioxyamphetamine. The important cardiovascular 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).