Naltrexone ameliorates functional network abnormalities in alcohol‐dependent individuals

Abstract

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 characterized. In the current study, we examined the effects of 50‐mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly‐drug‐dependent individuals compared with 36 healthy volunteers. Graph theoretic and network‐based statistical analysis of resting‐state functional magnetic resonance imaging (MRI) data revealed that alcohol‐dependent subjects had reduced functional connectivity of a dispersed network compared with 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. Naltrexone failed to have an effect on the local efficiency in abstinent poly‐substance‐dependent individuals. Across groups, local efficiency was associated with substance, but no 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.

Neuroimaging findings from an experimental pharmacology trial of naltrexone in heavy drinkers of East Asian descent

“…The few naltrexone studies that have examined functional connectivity vary in analysis parameters, populations of interest, and study designs. These studies have shown that naltrexone modulates connectivity between ACC and hippocampus as a function of childhood adversity during an emotional priming task among alcohol-dependent individuals (Savulich et al, 2017), and that naltrexone improves local network efficiency in alcohol dependent individuals, reaching that of healthy controls (Morris et al, 2018). Most notably, in a study of methamphetamine users, naltrexone decreased connectivity between precuneus and sensorimontor regions and increased connectivity between dorsal striatum and precuneus with frontal regions (Courtney et al, 2016).…”

Better Together? Coupling Pharmacotherapies and Cognitive Interventions With Non-invasive Brain Stimulation for the Treatment of Addictive Disorders

“…With regard to pharmacotherapies, while their action on cortical excitability and brain plasticity have been studies, it will be also critical to define how medications currently used for AD modulate brain activity and connectivity. For example, naltrexone, a medication commonly used in patients with alcohol and opioid use disorders, has been shown to modulate brain connectivity (Morris et al, 2018;Elton et al, 2019). Since NIBS also has a modulatory effect on brain connectivity, particularly when applied to network nodes (Eldaief et al, 2011), future research should investigate whether these effects can be combined in a synergistic fashion.…”

A preliminary randomized clinical trial of naltrexone reduces striatal resting state functional connectivity in people with methamphetamine use disorder

“…Neuroimaging studies of alcohol use disorder demonstrate the effects of naltrexone on brain function and connectivity (Lukas et al, 2013; Mann et al, 2014; Morris et al, 2017; Spagnolo et al, 2014). We extend these results to individuals with MA use disorder and show a reduction in striatolimbic RSFC in the XR-NTX group compared to a Placebo group.…”