Neurotoxicity of drugs of abuse - the case of methylenedioxy amphetamines (MDMA, ecstasy ), and amphetamines

High doses of MDMA (ecstasy) and stimulant amphetamines like methamphetamine (speed) are clearly neurotoxic in laboratory animals. MDMA selectively damages central serotonergic nerve terminals, while amphetamines harm both serotonergic and dopaminergic systems. In human drug users, evidence suggests residual alterations of serotonergic transmission from MDMA, with possible partial recovery after long-term abstinence, though functional impairments may persist. Subtle cognitive impairments, especially memory deficits, are the most consistent findings. For methamphetamine, preliminary evidence indicates dopaminergic system alterations may persist after years of abstinence, linked to motor and cognitive performance deficits.

Study at a glance

Abstract

Ecstasy (MDMA, 3,4-methylendioxymethamphetamine) and the stimulants methamphetamine (METH, speed) and amphetamine are popular drugs among young people, particularly in the dance scene. When given in high doses both MDMA and the stimulant amphetamines are clearly neurotoxic in laboratory animals. MDMA causes selective and persistent lesions of central serotonergic nerve terminals, whereas amphetamines damage both the serotonergic and dopaminergic systems. In recent years, the question of ecstasy-induced neurotoxicity and possible functional sequelae has been addressed in several studies in drug users. Despite large methodological problems, the bulk of evidence suggests residual alterations of serotonergic transmission in MDMA users, although at least partial recovery may occur after long-term abstinence. However, functional sequelae may persist even after longer periods of abstinence. To date, the most consistent findings associate subtle cognitive impairments with ecstasy use, particularly with memory. In contrast, studies on possible long-term neurotoxic effects of stimulant use have been relatively scarce. Preliminary evidence suggests that alterations of the dopaminergic system may persist even after years of abstinence from METH, and may be associated with deficits in motor and cognitive performance. In this paper, we will review the literature focusing on human studies.