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Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery

Published version
Peer-reviewed

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Authors

Savulich, G 
Riccelli, R 
Morgado Correia, Marta  ORCID logo  https://orcid.org/0000-0002-3231-7040
Deakin, JFW 

Abstract

Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.

Description

Keywords

Adult, Adult Survivors of Child Adverse Events, Alcoholism, Amygdala, Brain, Case-Control Studies, Cocaine-Related Disorders, Cross-Over Studies, Cues, Double-Blind Method, Female, Functional Neuroimaging, Gyrus Cinguli, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Naltrexone, Narcotic Antagonists, Neural Pathways, Opioid-Related Disorders, Prefrontal Cortex, Substance-Related Disorders, Young Adult

Journal Title

Translational Psychiatry

Conference Name

Journal ISSN

2158-3188
2158-3188

Volume Title

7

Publisher

Nature Publishing Group
Sponsorship
Medical Research Council (MC_UU_00005/14)
The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: this article presents independent research funded by the MRC as part of their addiction initiative (Grant Number G1000018). George Savulich was funded by a grant from the Wallitt Foundation.