The substituted amphetamines MDMA (Ecstasy) and methamphetamine (METH, ice, speed) are increasingly popular among party-drug users. Human studies of their acute and long-term adverse effects are often ambiguous due to confounding factors. Animal models show that intravenous METH is a potent reinforcer, while MDMA enhances social behavior. Brief exposure to either drug can cause long-term reductions in dopamine, serotonin, and noradrenaline in the brain and alter receptor and transporter proteins, though whether this reflects neurotoxicity remains unclear, especially for MDMA. Lasting changes in social behavior, anxiety, depressive symptoms, and memory have been observed in rats, matching some human findings. MDMA/METH combinations may produce greater adverse effects than either drug alone, a concern given that party drug users may frequently encounter this combination.
MDMA (Ecstasy) produces feelings of love and closeness in humans and prosocial effects in animals. In male Wistar rats, a moderate dose (5 mg/kg) increased social interaction, specifically general investigation of other rats while decreasing anogenital sniffing. Analysis of neural activation across 39 brain regions showed that MDMA given in a social context caused considerably greater brain activation than the same dose given to solitary rats. Six brain regions—including the caudate-putamen, medial preoptic area, paraventricular thalamic nucleus, central amygdala, ventromedial hypothalamic nucleus, and medial amygdala—showed augmented activation in the social-MDMA group. The nucleus accumbens, ventral tegmental area, and periaqueductal grey were activated only when MDMA was combined with social interaction. These findings suggest MDMA modulates neural circuits regulating affiliative behavior, possibly via oxytocin.