Recreational ecstasy use and the neurotoxic potential of MDMA: current status of the controversy and methodological issues.

The controversy over possible MDMA-induced serotonergic neurotoxicity in human recreational ecstasy users is examined critically in light of recent research findings. Although the designs of such studies have improved considerably since the 1990s, the evidence to date remains equivocal for a number of reasons, including (1) inconsistent findings on the existence and reversibility of persistent ecstasy-related serotonergic and cognitive deficits; (2) lack of clear association between changes in brain imaging measures and functional deficits attributed to MDMA-induced neurotoxicity; (3) the contribution of concomitant cannabis or other drug use to both brain imaging abnormalities and cognitive deficits; (4) methodological shortcomings such as failure to adequately match samples of ecstasy users and controls; (5) the questionable relevance of animal models of MDMA-induced neurotoxicity to typical human patterns of ecstasy use; and (6) the potential role of inherent pre-drug deficits in serotonergic systems, impulse control and executive cognitive function that may predispose to excessive use of drugs including ecstasy. Given the retrospective nature of nearly all studies of ecstasy users to date, the controversy over whether MDMA has ever caused neurotoxicity or cognitive deficit in human ecstasy users is likely to continue for some time without resolution.