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Clinical Trial
. 2018 Jul;43(4):254-261.
doi: 10.1503/jpn.170036.

Effects of extended-release naltrexone on the brain response to drug-related stimuli in patients with opioid use disorder

Zhenhao Shi  1 , An-Li Wang  1 , Kanchana Jagannathan  1 , Victoria P Fairchild  1 , Charles P O'Brien  1 , Anna Rose Childress  1 , Daniel D Langleben  1
Affiliations
Clinical Trial

Effects of extended-release naltrexone on the brain response to drug-related stimuli in patients with opioid use disorder

Zhenhao Shi et al. J Psychiatry Neurosci. 2018 Jul.

Abstract

Background: Heightened response to drug-related cues is a hallmark of addiction. Extended-release naltrexone (XR-NTX) is a US Food and Drug Administration-approved pharmacotherapy for relapse prevention in patients with opioid use disorder (OUD). In these patients, XR-NTX has been shown to reduce brain responses to opioid-related visual stimuli. To assess the biomarker potential of this phenomenon, it is necessary to determine whether this effect is limited to opioid-related stimuli and whether it is associated with key OUD symptoms.

Methods: Using functional MRI (fMRI), we measured the brain responses to opioid-related and control (i.e., sexual and aversive) images in detoxified patients with OUD before, during and after XR-NTX treatment. Craving and withdrawal severity were evaluated using clinician- and self-administered instruments during each session.

Results: We included 24 patients with OUD in our analysis. During XR-NTX treatment, we found reduced responses to opioid-related stimuli in the nucleus accumbens (NAcc) and medial orbitofrontal cortex (mOFC). The reduction in mOFC response was specific to the opioid-related stimuli. The reduced NAcc and mOFC opioid cue reactivity was correlated with reduction in clinician-assessed and self-reported withdrawal symptoms, respectively.

Limitations: The study was not placebo-controlled owing to ethical, safety and feasibility concerns.

Conclusion: Extended-release naltrexone reduces the NAcc and mOFC cue reactivity in patients with OUD. This effect is specific to opioid-related stimuli in the mOFC only. The reduction in neural response to opioid-related stimuli is more robust in patients with greater decline in withdrawal severity. Our results support the clinical utility of mesocorticolimbic cue reactivity in monitoring the XR-NTX treatment outcomes and highlight the link between opioid withdrawal symptomatology and neural opioid cue reactivity.

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Conflict of interest statement

Competing interests: C. O’Brien declares having received consulting fees from Alkermes plc. D. Langleben received honoraria from Alkermes plc in 2016 and 2017 for participation on its scientific advisory board. No other competing interests declared.

Figures

Fig. 1
Fig. 1
(A) The nucleus accumbens (NAcc) response to cues during the pretreatment and on-treatment sessions. (B) The medial orbitofrontal cortex (mOFC) response to cues during the pre- and on-treatment sessions. (C) Results of whole-brain analysis of variance showing significant session × stimulus interaction in the NAcc and mOFC. The error bar represents standard error of mean; *p < 0.05; **p < 0.01.
Fig. 2
Fig. 2
(A) Correlation between the change in Clinical Opiate Withdrawal Scale (COWS) scores and the change in nucleus accumbens (NAcc) response to opioid drug cues. (B) Correlation between the change in self-reported opioid withdrawal and the change in medial orbitofrontal cortex (mOFC) response to opioid drug cues. All change calculations reflect the difference between pretreatment and on-treatment assessments. Δ = pretreatment minus on-treatment; **p < 0.01; ***p < 0.005.
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References

    1. Naghavi M, Wang H, Lozano R, et al. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385:117–71. - PMC - PubMed
    1. National Institute on Drug Abuse. Overdose death rates. North Bethesda (MD): the Institute; 2015.
    1. Wise RA, Koob GF. The development and maintenance of drug addiction. Neuropsychopharmacology. 2014;39:254–62. - PMC - PubMed
    1. Johnson SW, North RA. Opioids excite dopamine neurons by hyper-polarization of local interneurons. J Neurosci. 1992;12:483–8. - PMC - PubMed
    1. Hyman SE, Malenka RC, Nestler EJ. Neural mechanisms of addiction: the role of reward-related learning and memory. Annu Rev Neurosci. 2006;29:565–98. - PubMed

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