REDUCED STRIATAL DOPAMINE TRANSPORTER DENSITY IN ABSTINENT METHAMPHETAMINE AND METHCATHINONE USERS - EVIDENCE FROM POSITRON-EMISSION-TOMOGRAPHY STUDIES WITH [C-11] WIN-35,428

Methamphetamine and methcathinone are psychostimulant drugs with high potential for abuse. In animals, methamphetamine and related drugs are known to damage brain dopamine (DA) neurons, and this damage has rece ntly been shown to be detectable in living nonhuman primates by means of positron emission tomography (PET) with [C-11]WIN-35,428, a DA tran sporter (DAT) ligand. The present studies determined whether living hu mans with a history of methamphetamine or methcathinone abuse showed e vidence of lasting decrements in brain DAT density. PET studies were p erformed in 10 control subjects, six abstinent methamphetamine users, four abstinent methcathinone users, and three patients with Parkinson' s disease (PD). On average, subjects had abstained from amphetamine us e for similar to 3 years. Before PET studies, all subjects underwent u rine and blood toxicology screens to rule out recent drug use. Compare d with controls, abstinent methamphetamine and methcathinone users had significant decreases in DAT density in the caudate nucleus (-23 and -24%, respectively) and putamen (-25 and -16%, respectively). Larger d ecreases in DAT density were evident in patients with PD (47 and 68% i n caudate and putamen, respectively). Neither methamphetamine nor meth cathinone users showed clinical signs of parkinsonism. Persistent redu ctions of DAT density in methamphetamine and methcathinone users are s uggestive of loss of DAT or loss of DA terminals and raise the possibi lity that as these individuals age, they may be at increased risk for the development of parkinsonism or neuropsychiatric conditions in whic h brain DA neurons have been implicated.