Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol-dependent individuals

Samuel Turton,Alessandro Colasanti,Eugenii A Rabiner,Roger N Gunn,Gemma Dawe,Alan Brailsford,Stafford L Lightman,Mark C Parkin,Adam Waldman,David J Nutt,James Fm Myers,Inge Mick,Ashwin Venkataraman,Claire Durant,Anne Lingford-Hughes

doi:10.1038/s41380-018-0107-4

Abstract

Addiction has been proposed as a ‘reward deficient’ state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [11C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [11C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions.

Highlights

Electronic supplementary material The online version of this article contains supplementary material, which is available to authorised users.Alcohol dependence (AD) affects 4% of adults in Europe and 4.7% in the United States, and globally 3.3 million deaths per year (5.9% of deaths worldwide) are attributed to London, UK Centre for Restorative Neuroscience, Division of Brain Sciences, Imperial College London, London, UK Henry Wellcome Laboratories for Integrative Neuroscience &Endocrinology, University of Bristol, Bristol, UK harmful alcohol use [1]
We have demonstrated a blunted dexamphetamine-induced endogenous opioid release in the brain for the first time in abstinent alcohol-dependent individuals with [11C]carfentanil positron emission tomography (PET)
Our data in AD are consistent with our previous study in gambling disorder where we found blunted dexamphetamine-induced opioid release [27]

Summary

Introduction

Psychosocial approaches are the mainstay treatment of AD but effective relapse prevention medications, including the opioid antagonists naltrexone and nalmefene, are available [5,6,7]. Using functional magnetic resonance imaging (fMRI), naltrexone and nalmefene have been shown to reduce brain responses in the mesolimbic pathway to salient alcohol cues or exposure [10, 11]. These medications do not help everyone and so a better understanding of opioid system function in alcoholism is required to develop improved therapies and better target individuals with current medication

Methods

Results

Conclusion