Naltrexone ameliorates functional network abnormalities in alcohol‐dependent individuals

• DOI: 10.1111/adb.12503
• Publication Date: 2017-02-28T21:56:50Z
• Authors: Laurel S. Morris; Kwangyeol Baek; Roger Tait; Rebecca Elliott; Karen D. Ersche; Remy Flechais; John McGonigle; Anna Murphy; Liam J. Nestor; Csaba Orban; Filippo Passetti; Louise M. Paterson; Ilan Rabiner; Laurence Reed; Dana Smith; John Suckling; Eleanor M. Taylor; Edward T. Bullmore; Anne R. Lingford‐...; Bill Deakin; David J. Nutt; Barbara J. Sahakian; Trevor W. Robbins; Valerie Voon
• Keywords: Male; multiple drug abuse; drug dependence; medial orbitofrontal cortex; Human Neuroimaging Study; drugs used in the treatment of addiction; supplementary motor area; 0302 clinical medicine; middle aged; Neural Pathways; nuclear magnetic resonance imaging; middle frontal gyrus; pathophysiology; right hemisphere; alcoholism; alcohol; adult; cingulate gyrus; drug effect; single drug dose; Substance Abuse; Brain; 11 Medical And Health Sciences; Middle Aged; Magnetic Resonance Imaging; Healthy Volunteers; Naltrexone; opiate; 3. Good health; Alcoholism; female; priority journal; olfactory bulb; young adult; Female; addiction; naltrexone; CAH11-01-01 - computer science; onset age; Adult; RM; diagnostic imaging; Substance-Related Disorders; brain; 610; Addiction; cocaine; substance use; functional neuroimaging; Article; 17 Psychology And Cognitive Sciences; Young Adult; 03 medical and health sciences; male; nerve tract; parahippocampal gyrus; 616; drug mechanism; Humans; controlled study; human; normal human; ICCAM Consortium; Functional Neuroimaging; functional connectivity; functional magnetic resonance imaging; major clinical study; middle occipital gyrus; exploratory research; placebo; left hemisphere; Alcohol Deterrents

AbstractNaltrexone, 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.