Naltrexone ameliorates functional network abnormalities in alcohol‐dependent individuals

Laurel S Morris,Barbara J Sahakian,Bill Deakin,John Suckling,Ilan Rabiner,Roger Tait,Filippo Passetti,Dana Smith,Louise M Paterson,Anna Murphy,John Mcgonigle,Kwangyeol Baek,Laurence Reed,Karen D Ersche,Valerie Voon,Remy Flechais,Edward T Bullmore,Trevor W Robbins,Csaba Orban,Anne Lingford-Hughes ,David Nutt ,Richard M Elliott ,Eleanor Taylor ,Liam Nestor

doi:10.1111/adb.12503

Laurel S Morris, Barbara J Sahakian + Show 22 more

Open Access

https://doi.org/10.1111/adb.12503

Copy DOI

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.

Highlights

Substance use disorders are complex, multifaceted disorders often characterized by cycles of intoxication, withdrawal and craving, propagating substance-seeking behaviours that persist despite often-severe negative consequences
We examined the effects of a single dose of the mu-opioid receptor (MOR) antagonist naltrexone in alcohol dependence (AD) and poly-drug substance dependence (SD) subjects
Local efficiency in poly-drug SD was not affected by naltrexone and was positively associated with exposure to drugs of abuse

Summary

Introduction

Substance use disorders are complex, multifaceted disorders often characterized by cycles of intoxication, withdrawal and craving, propagating substance-seeking behaviours that persist despite often-severe negative consequences. The social, health and economic costs of substance dependence (SD) are high (Nutt et al 2010); yet the universal efficacy of currently available treatments is limited, and the mechanisms of action of such treatments are poorly understood (Sturgess et al 2011; Tiffany et al 2012). The current study aims to examine the effects of naltrexone on the neural network changes associated with SD, in poly-drug SD and AD. Like some other drugs of abuse, increases mesolimbic dopamine (DA) release in rodents and humans (Boileau et al 2003), one mechanism by which it exerts its primary reinforcing effects (Dichiara & Imperato 1988; Everitt, Dickinson, & Robbins 2001).

Methods

Results

Conclusion