Naltrexone ameliorates functional network abnormalities in alcohol dependent individuals

Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterised. In the current study, we examined the effects of 50mg naltrexone compared to placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug dependent individuals compared to 36 healthy volunteers. Graph theoretic and network based statistical analysis of resting-state functional MRI data revealed that alcohol dependent subjects had reduced functional connectivity of a dispersed network compared to both poly-drug dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol dependent individuals, to the same levels as healthy volunteers (group x naltrexone interaction effect, p=0.012). Naltrexone failed to have an effect on the local efficiency in abstinent poly-substance dependent individuals (group x naltrexone interaction, p=0.215). Across groups, local efficiency was associated with substance but not alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely the amelioration of disrupted network topology.