Neurotoxicity of Methamphetamine and 3,4-methylenedioxymethamphetamine

Amphetamines, including methamphetamine and MDMA, are psychostimulants abused for their stimulant, euphoric, empathogenic, and hallucinogenic effects. These effects arise from acute increases in dopamine and serotonin neurotransmission. Beyond these acute effects, the drugs cause persistent damage to dopamine and serotonin nerve terminals through mechanisms such as excitotoxicity, mitochondrial damage, and oxidative stress. The review also covers emerging non-neuronal mechanisms that may contribute to this damage and the neuropsychiatric consequences of terminal damage. It compares methamphetamine and MDMA to other abused substances like cathinone (khat) and novel synthetic amphetamines known as 'bath salts'.

Study at a glance

Abstract

Amphetamines are a class of psychostimulant drugs that are widely abused for their stimulant, euphoric, empathogenic and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, methamphetamine and 3,4 methylenedioxymethamphetamine (MDMA) produce persistent damage to dopamine and serotonin nerve terminals. This review summarizes the numerous interdependent mechanisms including excitotoxicity, mitochondrial damage and oxidative stress that have been demonstrated to contribute to this damage. Emerging non-neuronal mechanisms by which the drugs may contribute to monoaminergic terminal damage, as well as the neuropsychiatric consequences of this terminal damage are also presented. Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) have similar chemical structures and pharmacologic properties compared to other abused substances including cathinone (khat), as well as a relatively new class of novel synthetic amphetamines known as ‘bath salts’ that have gained popularity amongst drug abusers.