Methadone maintenance therapy (MMT), a standard treatment for opiate- dependent patients purportedly produces beneficial effects through its action as a substitute in an endogenous opioid deficiency syndrome. Nonetheless, direct evidence of persistant abnormalities in brain function of opiate-dependent patients, who are free of medication and illicit drugs of abuse, is lacking. The purpose of this study is to address this question by using the [F-18] fluorodeoxy glucose (FDG) method and positron emission tomography (PET) to assay regional cerebral metabolic rate(s) for glucose (rCMRglc), and index of local brain function. Subjects who have histories of opiate dependence will be compared with nonopiate-abusing control subjects matched for socioeconomic status, gender, and age. The proposed research will ask the following questions: 1) Is opiate dependence associated with persistent abnormalities in regional brain function, as assessed by measurement (as evidenced by differences in) of rCMRglc; and 2) Are potential abnormalities in rCMRglc, seen in abstinent patients at least six months after cessation of MMT as compared with controls, absent in patients who have received MMT for at least 6 months? Answers to these questions would have bearing on the theory that long-term deficiency of endogenous opioids leads to persistent cerebral dysfunction that can be ameliorated by MMT. The long-term goals of this project and its possible extensions are a comprehensive understanding of the relationship between neuroanatomical, neurochemical and clinical factors pertaining to opiate addiction, and its treatment, and the design of more effective therapeutic strategies.