Corticolimbic dysregulation and chronic methamphetamine abuse.

AIMS This review aims to present and interpret evidence that methamphetamine dependence is associated with disorder of brain function that is required for top-down control of behavior. APPROACH Presented here are findings from brain imaging studies of human research participants with histories of chronic methamphetamine abuse in the context of functional consequences and implications for treatment of their dependence on methamphetamine. FINDINGS Brain imaging studies have revealed differences in the brains of research participants who have used methamphetamine chronically and then abstained from taking the drug, compared with healthy control subjects. These abnormalities are prominent in cortical and limbic systems, and include deficits in markers of dopaminergic and serotonergic neurotransmitter systems, differences in glucose metabolism and deficits in gray matter. These abnormalities accompany cognitive deficits, including evidence of impaired inhibitory control. CONCLUSION Cortical deficits in abstinent methamphetamine abusers can affect a wide range of functions that can be important for success in maintaining drug abstinence. These include but are not limited to modulation of responses to environmental stimuli as well as internal triggers that can lead to craving and relapse. Potential therapies may combine behavioral approaches with medications that can improve cognitive control.