PMID- 29485031
OWN - NLM
STAT- Publisher
LR  - 20240227
IS  - 1488-2434 (Electronic)
IS  - 1180-4882 (Linking)
VI  - 43
IP  - 3
DP  - 2018 Feb 23
TI  - Effects of extended-release naltrexone on the brain response to drug-related 
      stimuli in patients with opioid use disorder.
PG  - 170036
LID - 10.1503/jpn.170036 [doi]
AB  - 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.
FAU - Shi, Zhenhao
AU  - Shi Z
AD  - From the Department of Psychiatry, University of Pennsylvania Perelman School of 
      Medicine, Philadelphia, Pa. (Shi, Wang, Jagannathan, Fairchild, O'Brien, 
      Childress, Langleben); the Department of Psychiatry, Icahn School of Medicine at 
      Mount Sinai, New York, NY (Wang); the Annenberg Public Policy Center, University 
      of Pennsylvania, Philadelphia, Pa. (Langleben); and the Corporal Michael J. 
      Crescenz Veterans Administration Medical Center, Philadelphia, Pa. (Langleben).
FAU - Wang, An-Li
AU  - Wang AL
AD  - From the Department of Psychiatry, University of Pennsylvania Perelman School of 
      Medicine, Philadelphia, Pa. (Shi, Wang, Jagannathan, Fairchild, O'Brien, 
      Childress, Langleben); the Department of Psychiatry, Icahn School of Medicine at 
      Mount Sinai, New York, NY (Wang); the Annenberg Public Policy Center, University 
      of Pennsylvania, Philadelphia, Pa. (Langleben); and the Corporal Michael J. 
      Crescenz Veterans Administration Medical Center, Philadelphia, Pa. (Langleben).
FAU - Jagannathan, Kanchana
AU  - Jagannathan K
AD  - From the Department of Psychiatry, University of Pennsylvania Perelman School of 
      Medicine, Philadelphia, Pa. (Shi, Wang, Jagannathan, Fairchild, O'Brien, 
      Childress, Langleben); the Department of Psychiatry, Icahn School of Medicine at 
      Mount Sinai, New York, NY (Wang); the Annenberg Public Policy Center, University 
      of Pennsylvania, Philadelphia, Pa. (Langleben); and the Corporal Michael J. 
      Crescenz Veterans Administration Medical Center, Philadelphia, Pa. (Langleben).
FAU - Fairchild, Victoria P
AU  - Fairchild VP
AD  - From the Department of Psychiatry, University of Pennsylvania Perelman School of 
      Medicine, Philadelphia, Pa. (Shi, Wang, Jagannathan, Fairchild, O'Brien, 
      Childress, Langleben); the Department of Psychiatry, Icahn School of Medicine at 
      Mount Sinai, New York, NY (Wang); the Annenberg Public Policy Center, University 
      of Pennsylvania, Philadelphia, Pa. (Langleben); and the Corporal Michael J. 
      Crescenz Veterans Administration Medical Center, Philadelphia, Pa. (Langleben).
FAU - O'Brien, Charles P
AU  - O'Brien CP
AD  - From the Department of Psychiatry, University of Pennsylvania Perelman School of 
      Medicine, Philadelphia, Pa. (Shi, Wang, Jagannathan, Fairchild, O'Brien, 
      Childress, Langleben); the Department of Psychiatry, Icahn School of Medicine at 
      Mount Sinai, New York, NY (Wang); the Annenberg Public Policy Center, University 
      of Pennsylvania, Philadelphia, Pa. (Langleben); and the Corporal Michael J. 
      Crescenz Veterans Administration Medical Center, Philadelphia, Pa. (Langleben).
FAU - Childress, Anna Rose
AU  - Childress AR
AD  - From the Department of Psychiatry, University of Pennsylvania Perelman School of 
      Medicine, Philadelphia, Pa. (Shi, Wang, Jagannathan, Fairchild, O'Brien, 
      Childress, Langleben); the Department of Psychiatry, Icahn School of Medicine at 
      Mount Sinai, New York, NY (Wang); the Annenberg Public Policy Center, University 
      of Pennsylvania, Philadelphia, Pa. (Langleben); and the Corporal Michael J. 
      Crescenz Veterans Administration Medical Center, Philadelphia, Pa. (Langleben).
FAU - Langleben, Daniel D
AU  - Langleben DD
AD  - From the Department of Psychiatry, University of Pennsylvania Perelman School of 
      Medicine, Philadelphia, Pa. (Shi, Wang, Jagannathan, Fairchild, O'Brien, 
      Childress, Langleben); the Department of Psychiatry, Icahn School of Medicine at 
      Mount Sinai, New York, NY (Wang); the Annenberg Public Policy Center, University 
      of Pennsylvania, Philadelphia, Pa. (Langleben); and the Corporal Michael J. 
      Crescenz Veterans Administration Medical Center, Philadelphia, Pa. (Langleben).
LA  - eng
GR  - R00 HD084746/HD/NICHD NIH HHS/United States
GR  - T32 DA028874/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20180223
PL  - Canada
TA  - J Psychiatry Neurosci
JT  - Journal of psychiatry & neuroscience : JPN
JID - 9107859
EDAT- 2018/02/28 06:00
MHDA- 2018/02/28 06:00
CRDT- 2018/02/28 06:00
PHST- 2018/02/28 06:00 [entrez]
PHST- 2018/02/28 06:00 [pubmed]
PHST- 2018/02/28 06:00 [medline]
AID - 10.1503/jpn.170036 [pii]
AID - 10.1503/jpn.170036 [doi]
PST - aheadofprint
SO  - J Psychiatry Neurosci. 2018 Feb 23;43(3):170036. doi: 10.1503/jpn.170036.