Effects of the 2-Adrenergic Agonist Clonidine on the Pharmacodynamics and Pharmacokinetics of 3,4- Methylenedioxymethamphetamine in Healthy Volunteers

Abstract

The mechanism of action of 3,4-methylenedioxymethamphet-amine (MDMA; ecstasy) involves the carrier-mediated and po-tentially vesicular release of monoamines. We assessed the effects of the sympatholytic 2-adrenergic receptor agonist clonidine (150 g p.o.), which inhibits the neuronal vesicular release of norepinephrine, on the cardiovascular and psycho-tropic response to MDMA (125 mg p.o.) in 16 healthy subjects. The study used a randomized, double-blind, placebo-con-trolled crossover design with four experimental sessions. The administration of clonidine 1 h before MDMA reduced the MDMA-induced increases in plasma norepinephrine concen-trations and blood pressure but only to the extent that clonidine lowered norepinephrine levels and blood pressure compared with placebo. Thus, no interaction was found between the cardiovascular effects of the two drugs. Clonidine did not affect the psychotropic effects or pharmacokinetics of MDMA. The lack of an interaction of the effects of clonidine and MDMA indicates that vesicular release of norepinephrine, which is inhibited by clonidine, does not critically contribute to the ef-fects of MDMA in humans. Although clonidine may be used in the treatment of stimulant-induced hypertensive reactions, the present findings do not support a role for 2-adrenergic recep-tor agonists in the prevention of psychostimulant dependence