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.
A single oral weight-adjusted dose of MDMA (1.4 mg/kg) produced similar plasma concentrations and positive subjective effects in healthy recreational users regardless of gender or CYP2D6 and COMT genotypes. Female subjects experienced more intense physiological effects (increased heart rate and oral temperature) and negative effects (dizziness, sedation, depression, psychotic symptoms). Genotypes of COMT val158met or 5-HTTLPR with high functionality led to greater cardiovascular effects, while low-functionality genotypes were linked to negative subjective effects. The contribution of MDMA pharmacokinetics to gender differences in drug effects appears negligible; instead, 5-HTTLPR and COMT val158met genotypes play a major role.