A resurgence in opiate abuse and dependence is occurring in several major U.S. cities, including Boston. Unfortunately, few studies have addressed the consequences of opiate abuse and dependence on cerebral metabolism or perfusion in human subjects. Additionally, no study to date has examined the neurochemical effects of the most widely utilized intervention for opiate abuse, methadone administration. Methadone maintenance (MM) has demonstrated efficacy in improving overall health and psychiatric symptoms in opiate abusers, improving their ability to function in society and reducing the economic costs of opiate addiction. Moreover, NIDA has recently recommended expanded use of MM for treatment of opiate addition (NIDA Notes, Nov./Dec. 1997). This proposal responds to RFA DA 98-004 entitled """"""""Neurobiological Effects of Drug Addiction Therapies."""""""" The purpose of this 5-year study is to examine the effects of methadone maintenance treatment on cerebral function in opiate dependent drug abusers, utilizing phosphorus magnetic resonance spectroscopic imaging (31P MRSI). Patients will undergo 31P MRSI at entry into a methadone maintenance treatment program, and have repeat scans after 6, 12 and 24 months of treatment. The relationship between response to treatment and cerebral function at initiation and during maintenance will be examined. Cerebral metabolic changes during methadone treatment will be compared to intensity and patterns of baseline and continued drug use, baseline and treatment-altered neurocognitive function, gender, ethnicity and psychiatric status. On the basis of cross sectional pilot studies, we hypothesize that opiate-dependent polydrug abusers will have baseline 31P MRSI abnormalities indicative of neuronal/glial membrane and bioenergetic dysfunction in both whole brain and in frontal, circulate and temporal cortices, as well as functional deficits in learning, recall, and attention. Additionally, we hypothesize that 31P MRSI abnormalities will improve in patients retained over a 2-year period of MM, and that the degree of 31P MRSI improvement will correlate with the degree of neurocognitive and Addiction Severity Index score improvement. This study will provide important new information on the nature of changes in brain chemistry associated with positive outcome (long term MM retention with minimal illicit drug use), intermediate outcome (MM retention with continued drug use) and negative outcome (early attrition from MM treatment). This information may be directly relevant to the design of more effective therapies for opiate dependence which will provide better symptomatic relief, resulting in reduced drug abuse and increased patient functionality in the high proportion of opiate dependent patients who do not experience optimal MM treatment outcomes.
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