Mephedrone: Public health risk, mechanisms of action, and behavioral effects

The recent shortage of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) has led to an increased demand for alternative amphetamine-like drugs such as the synthetic cathinone, 4-methylmethcathinone (mephedrone). Despite the re-classification of mephedrone as a Class B restricted substance by the United Kingdom and restrictive legislation by the United States, international policy regarding mephedrone control is still developing and interest in synthetic amphetamine-like drugs could drive the development of future mephedrone analogues. Currently, there is little literature investigating the mechanism of action and long-term effects of mephedrone. As such, we reviewed the current understanding of amphetamines, cathinones, and cocaine emphasizing the potentially translational aspects to mephedrone, as well as contrasting with the work that has been done specifically on mephedrone in order to present the current state of understanding of mephedrone in terms of its risks, mechanisms, and behavioral effects. Emerging research suggests that while there are structural and behavioral similarities of mephedrone with amphetamine-like compounds, it appears that serotonergic signaling may mediate more of mephedrone's effects unlike the more dopaminergic dependent effects observed in traditional amphetamine-like compounds. As new designer drugs are produced, current and continuing research on mephedrone and other synthetic cathinones should help inform policymakers' decisions regarding the regulation of novel 'legal highs.'