Neurotoxicity Induced by Mephedrone: An up-to-date Review

Background: Mephedrone is a beta-ketoamphetamine belonging to the family of synthetic cathinones, an emerging class of designer drugs known for their hallucinogenic and psychostimulant properties as well as for their abuse potential. Objective: The aim of this review was to examine the emerging scientific literature on the possible mephedrone-induced neurotoxicity, yet not well defined due to the limited number of experimental studies, mainly carried on animal models. Materials and Methods: Relevant scientific articles were identified from international literature databases (Medline, Scopus, etc.) using the keywords: "Mephedrone", "4-MMC," " neurotoxicity," "neuropharmacology", "patents", "monoamine transporters" and "neurochemical effects". Results: Of the 498 sources initially found, only 36 papers were suitable for the review. Neurotoxic effect of mephedrone on 5-hydroxytryptamine (5-HT) and dopamine (DA) systems remains controversial. Although some studies in animal models reported no damage to DA nerve endings in the striatum and no significant changes in brain monoamine levels, some others suggested a rapid reduction in 5-HT and DA transporter function. Persistent serotonergic deficits were observed after binge like treatment in a warm environment and in both serotonergic and dopaminergic nerve endings at high ambient temperature. Oxidative stress cytotoxicity and an increase in frontal cortex lipid peroxidation were also reported. In vitro cytotoxic properties were also observed, suggesting that mephedrone may act as a reductant agent and can also determine changes in mitochondrial respiration. However, due to the differences in the design of the experiments, including temperature and animal model used, the results are difficult to compare. Conclusions: Further studies on toxicology and pharmacology of mephedrone are therefore necessary to establish an appropriate treatment for substance abuse and eventual consequences for public health.