Addiction Mechanisms, Phenomenology and Treatment

Reneman L, Reneman, L.

Of the designer drugs, the amphetamine analogues are the most popular and extensively studied, ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in particular. They are used recreationally with increasing popularity despite animal studies showing neurotoxic effects to serotonin (5-HT) and/or dopamine (DA) neurones. However, few detailed assessments of risks of these drugs exist in humans. Previously, there were no methods available for directly evaluating the neurotoxic effects of amphetamine analogues in the living human brain. However, development of in vivo neuroimaging tools have begun to provide insights into the effects of MDMA in human brain. In this review, contributions of brain imaging studies on the potential 5-HT and/or DA neurotoxic effects of amphetamine analogues will be highlighted in order to delineate the risks these drugs engender in humans, focusing on MDMA. An overview will be given of PET, SPECT and MR Spectroscopy studies employed in human users of these drugs. Most of these studies provide suggestive evidence that MDMA is neurotoxic to 5-HT neurones, and (meth)amphetamine to DA neurones in humans. These effects seem to be dose-related, leading to functional impairments such as memory loss, and are reversible in several brain regions. However most studies have had a retrospective design, in which evidence is indirect and differs in the degree to which any causative links can be implied between drug use and neurotoxicity. Therefore, at this moment, it cannot be ascertained that humans are susceptible to MDMA-induced 5-HT injury or (meth)amphetamine-induced DA injury. Finally, although little is known about other amphetamine analogues there are important questions as to the safety of these designer drugs as well, in view of the fact that they are chemically closely related to MDMA and some have been shown to be 5-HT neurotoxins in animals.