Effect of Naltrexone on Craving and Ethanol-Induced Brain Activity

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Findings from animal and human studies indicate that the rewarding properties of ethanol arise in part from a complex interaction between alcohol, endogenous opiods, and dopamine (DA) systems. Acute administration of ethanol increases the release of opioid peptides, which in turn, increases the release of DA in the mesocorticolimbic system. Naltrexone (NTX), an opioid receptor antagonist, has been studied widely in both preclinical and clinical research for the treatment of alcoholism. Numerous clinical studies have shown that short-term use of NTX in alcohol-dependent patients effectively prevents relapse and reduces the level of craving. This study will involve 60 alcoholic patients between the ages of 21-50 years of age who meet diagnostic criteria for alcohol dependence. Following detoxification, patients will be randomized, using a double-blind design, to receive NTX or placebo throughout the course of their hospitalization. fMRI scans involving ethanol infusions will be performed in order to investigate NTX's effect on the BOLD response associated with brain activity during the infusions. This protocol is the first study which involves administerinig IV alcohol to treatment-seeking alcohol dependent patients. Radification of the protocol by the IRB was prolonged due to extensive deliberations concerning patient safety. To date, four individuals have been enrolled in the study.