MDMA, methamphetamine and their combination: possible lessons for party drug users from recent preclinical research

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.

Study at a glance

Abstract

Abstract The substituted amphetamines 3,4‐methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) and methamphetamine (METH, ‘ice’, ‘speed’) are increasingly popular drugs amongst party‐drug users. Studies with humans have investigated the acute and possible long‐term adverse effects of these drugs, yet outcomes of such studies are often ambiguous due to a variety of confounding factors. Studies employing animal models have value in determining the acute and long‐term effects of MDMA and METH on brain and behaviour. Self‐administration studies show that intravenous METH is a particularly potent reinforcer in rats and other species. In contrast, MDMA appears to have powerful effects in enhancing social behaviour in laboratory animals. Brief exposure to MDMA or METH may produce long‐term reductions in dopamine, serotonin and noradrenaline in the brain and alterations in the density of various receptor and transporter proteins. However it is still unclear, particularly in the case of MDMA, whether this reflects a ‘neurotoxic’ effect of the drug. Lasting alterations in social behaviour, anxiety, depressive symptoms and memory have been demonstrated in laboratory rats given MDMA or METH and this matches long‐term changes reported in some human studies. Recent laboratory studies suggest that MDMA/METH combinations may produce greater adverse neurochemical and behavioural effects than either drug alone. This is of some concern given recent evidence that party drug users may be frequently exposed to this combination of drugs.