Two antagonists of opioid receptors are used for the treatment for AD: naltrexone (NTX) and nalmefene. Both antagonists reduce drinking and craving in alcoholic individuals in treatment and also in heavy drinkers. It is hypothesized that NTX works in part by occupying opioid receptors, preventing their binding by endogenous opioid peptides released upon alcohol intake, and in part by modest activation of the HPA axis (e.g. O'Brien et al. 2011; O'Malley et al. 2002). Activation of the HPA axis by the mechanism of disinhibition of the tonic mu opioid receptor inhibition is one of the pharmacological effects of NTX (Schluger et al. 1998). A substantial number of patients still do not respond to treatment, and family history of alcoholism was reported to be predictive of NTX response, suggesting the possibility that genetic factors may play a role in its effect (Rubio et al. 2005).
