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Prog Brain Res. 2016;223:253-67. doi: 10.1016/bs.pbr.2015.07.030. Epub 2015 Oct 21.

Opioid neuroscience for addiction medicine: From animal models to FDA approval for alcohol addiction.

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Karl E Rickles Professor of Psychiatry, Center for Neurobiology and Behavior, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:


Alcohol addiction is one of the most common and devastating diseases in the world. Given the tremendous heterogeneity of alcohol-addicted individuals, it is unlikely that one medication will help nearly all patients. Thus, there is a clear need to develop predictors of response to existing medications. Naltrexone is a mu opioid receptor antagonist which has been approved in the United States for treatment of alcohol addiction since 1994. It has limited efficacy, in part due to noncompliance, but many patients do not respond despite high levels of compliance. There are reports that a mis-sense single-nucleotide polymorphism (rs179919 or A118G) in the mu opioid receptor gene predicts a favorable response to naltrexone if an individual carries a "G" allele. This chapter will review the evidence for this hypothesis. The data suggest that the "G" allele has a complex role in alcohol addiction, increasing the rewarding valence of alcohol. Whether the G allele increases risk for alcoholism and whether it predisposes to a beneficial naltrexone response among alcohol-addicted persons must await additional research with large sample sizes of multiple ethnicities in prospective clinical trials.


Alcohol addiction; Naltrexone; Opioids; Pharmacogenetics; mu opioid receptor

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