While the specific dynamics of this circuit have yet to be resolved, these preclinical findings implicate that activity at delta and kappa opioid receptors, in addition to mu, may underlie the effects of naltrexone on alcohol-related phenotypes. This is consistent with human positron emission tomography (PET) studies documenting opioid receptor blockade at the standard therapeutic dose in alcohol dependent human subjects (Weerts et al., 2008). Specifically, while the naltrexone dose (50mg) blocked nearly all (about 94%) of mu opioid receptors with little variability across subjects, delta receptor blockade was lower (about 21%) but also highly variable, potentially explaining individual differences in treatment outcomes (Weerts et al., 2008).
