The kappa opioid receptor is associated with naltrexone-induced reduction of drinking and craving

Abstract Background Naltrexone is a non-selective opioid receptor antagonist used as a treatment for alcohol use disorders (AUD). However, only modest clinical effects have been observed, possibly because of limited knowledge on biological variables affecting the efficacy of naltrexone. We investigated the potential role of the kappa opioid receptor (KOR) in the therapeutic effect of naltrexone. Methods Forty-eight non-treatment seeking heavy drinkers (16 females) who met DSM-IV criteria for alcohol dependence participated in two alcohol drinking paradigms (ADPs), separated by a week of open label naltrexone 100 mg daily. Craving, assessed with the Alcohol Urge Questionnaire and Yale Craving Scale, and drinking behavior were recorded in each ADP. Prior to naltrexone initiation, KOR availability was determined in the amygdala, hippocampus, pallidum, striatum, cingulate, and prefrontal cortex using positron emission tomography (PET) with [ 11 C]-LY2795050. Results Participants reported lower levels of craving (YCS: -11 ± 1, p Conclusions The KOR is implicated in drinking and craving following naltrexone therapy in AUD.