Following the chronic use of methamphetamine, some individuals experience psychosis and anxiety. One reason may be the persistence of metabolite abnormalities in the brain of currently abstinent former methamphetamine users.In this study, N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr ϩ PCr), and choline-containing compound (Cho) levels were measured in the left and right basal ganglia using proton magnetic resonance spectroscopy (MRS) The number of abusers of the highly addictive drug methamphetamine has risen substantially worldwide and this has raised important concerns (Woolverton et al. 1984;Baberg et al. 1996;Shaw 1999). For example, chronic methamphetamine users show psychosis and anxiety following intoxication and withdrawal (Seivewright 2000). In addition, in some individuals, these psychiatric states may be present for months or even years after cessation of methamphetamine use (Sato et al. 1992;Iwanami et al. 1994;Buffenstein et al. 1999;Iyo et al. 1999). Although there are growing clinical observations on the neurotoxicology of chronic methamphetamine use, the mechanism by which the residual psychiatric problems arise from chronic methamphetamine NO . 3 use remains unknown. In rodents and baboons, methamphetamine has been shown to be toxic to dopaminergic and serotonergic neurons (Nakayama et al. 1993;Villemagne et al. 1998;Kokoshka et al. 1998). These neurotoxic effects include decreased concentrations of dopamine and serotonin in the brain and a reduction of dopamine and serotonin transporters, as well as loss of ATP and mitochondrial dysfunction in dopaminergic neurons (Chan et al. 1994;Burrows et al. 2000;Lotharius and O'Malley 2001). Human positron emission tomography (PET) studies have reported a significant reduction of dopamine transporter density in methamphetamine users Volkow et al. 2001), and that the reduction observed in methamphetamine users is associated with psychomotor impairment (Volkow et al. 2001). Recently, we have also found that the dopamine transporter density in methamphetamine users is inversely related to the length of methamphetamine use and the magnitude of psychiatric symptoms, including psychotic symptoms (Sekine et al. 2001).In vivo proton magnetic resonance spectroscopy ( 1 H MRS) and its variant 1 H MRS techniques provide insight into the metabolism of several endogenous brain chemicals (Miller 1991;Jackson 1992). A recent 1 H MRS study showed evidence for long-term metabolite alterations in currently abstinent former methamphetamine users, that is, reduced concentration of both N-acetylaspartate (NAA) and creatine plus phosphocreatine (Cr ϩ PCr) in the right basal ganglia (Ernst et al. 2000). However, it is unclear whether these abnormalities detected by 1 H MRS are related to psychiatric symptoms that are frequently observed in abstinent methamphetamine users.In this study, we investigated changes of the chemistry in the basal ganglia of abstinent methamphetamine users by 1 H MRS, and examined any relationship between the changes and clinical cha...