Pharmacology of Ecstasy (MDMA)

Abstract

Like mescaline, the primary psychoactive ingredient in peyote, MDMA belongs to a group of ring-substituted amphetamine congeners, commonly called “methoxylated amphetamines” (Fig. 6). The drug MDMA is a potent indirect monoaminergic agonist, which is thought to act by both increasing the release and inhibiting the reuptake of serotonin and, to a lesser extent, dopamine [14]. Serotonin is involved in the regulation of a variety of behavioral functions, including mood, anxiety, aggression, appetite, and sleep. Dopamine is the primary neuro-transmitter of the “reward pathway” and is involved in motivational processes such as reward and reinforcement. Norepinephrine has important roles in the process of attention and arousal. In vitro studies have shown, that MDMA causes release of serotonin, dopamine, and norepinephrine from synaptosomes [15, 16] and from rat brain slices [14]. In freely moving rats, MDMA increases both serotonin and dopamine release in the caudate [14]. In a similar study, MDMA increased dopamine release in awake rats, resulting in region-, time-, and dose-dependent behavior [17]. In rat brain synaptosomes, MDMA inhibited the uptake of serotonin and norepinephrine and, to a lesser extent, dopamine. The local administration of MDMA to the rat nucleus accumbens resulted in increases in the extracellular levels of both serotonin and dopamine in this region, which is part of the reward pathway activated by other abused substances such as amphetamine and cocaine. These actions in the nucleus accumbens may account for the euphoric effects produced by MDMA.