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'.
Mephedrone, a stimulant drug of abuse similar to methamphetamine and MDMA, does not damage serotonin nerve endings in the hippocampus. In a study of female C57BL mice, mephedrone alone did not cause persistent reductions in serotonin levels or in the serotonin transporter and tryptophan hydroxylase 2 markers. Methamphetamine and MDMA alone caused mild reductions in serotonin but did not change the other markers. Combining mephedrone with methamphetamine or MDMA did not increase toxicity to serotonin nerve endings beyond what either drug alone caused, unlike the increased toxicity seen with dopamine nerve endings when these drugs are taken together.