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

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.

• Authors: Zhenhao Shi, An-Li Wang, Kanchana Jagannathan, Victoria P Fairchild, Charles P O'Brien, Anna Rose Childress, Daniel D Langleben
• Journal: Journal of psychiatry & neuroscience : JPN (J Psychiatry Neurosci) Vol. 43 Issue 4 Pg. 254-261 (07 2018) ISSN: 1488-2434 [Electronic] Canada
• PMID: 29947607 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Delayed-Action Preparations
• Narcotic Antagonists
• Naltrexone

Topics

• Adult
• Craving (drug effects)
• Cues
• Delayed-Action Preparations (pharmacology, therapeutic use)
• Female
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Naltrexone (administration & dosage, pharmacology, therapeutic use)
• Narcotic Antagonists (pharmacology, therapeutic use)
• Neuroimaging
• Nucleus Accumbens (drug effects, physiopathology)
• Opioid-Related Disorders (drug therapy, physiopathology)
• Photic Stimulation
• Prefrontal Cortex (drug effects, physiopathology)
• Substance Withdrawal Syndrome (diagnosis, drug therapy)
• Young Adult