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Effects of opioid antagonism on functional MRI correlates of explicit and implicit threat processing in healthy volunteers.

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Title: Effects of opioid antagonism on functional MRI correlates of explicit and implicit threat processing in healthy volunteers.
Authors: Huneke, Nathan T. M. (AUTHOR), van Steenbergen, Henk (AUTHOR), Fagan, Harry A. (AUTHOR), Molteni, Laura (AUTHOR), Midveris, Algirdas (AUTHOR), Phillips, Naomi (AUTHOR), Darekar, Angela (AUTHOR), van der Wee, Nic J. A. (AUTHOR), Garner, Matthew (AUTHOR), Baldwin, David S. (AUTHOR)
Source: British Journal of Psychiatry. Jun2026, Vol. 228 Issue 6, p530-538. 9p.
Subjects: Naltrexone, Functional magnetic resonance imaging, Emotion regulation, Control (Psychology), Threat (Psychology), Human research subjects, Opioids
Abstract: Background: We need to identify novel, tractable therapeutic targets for anxiety disorders. Converging evidence suggests the endogenous opioid system plays a role in modulating affective processing, but its contribution to regulation of threat processing in humans remains unclear. Aims: We investigated the neural correlates of non-specific opioid antagonism on explicit and implicit regulation of threatening stimuli in healthy volunteers, using functional magnetic resonance imaging (fMRI). Method: In a randomised, double-blind, placebo-controlled, crossover design, 38 healthy participants received the opioid antagonist naltrexone (50 mg) or placebo before completing two tasks during fMRI: (a) a cognitive emotional reappraisal task probing explicit regulation and (b) a face-viewing task probing implicit processing. Results: Contrary to our hypothesis, we found naltrexone reduced distress ratings during the reappraisal task (p = 0.044) without impairing regulation success. Explicit regulation in the reappraisal task engaged lateral prefrontal regions similarly across drug conditions. However, naltrexone attenuated ventromedial prefrontal cortex, thalamus and caudate activation when viewing negative images. Naltrexone additionally altered ventromedial prefrontal cortex activity and in task-positive regions including right premotor area and frontal pole compared with placebo when viewing emotional faces. In particular, naltrexone increased left middle frontal gyrus activity when viewing fearful faces. Conclusions: Our results support a role for opioid signalling in automatic emotional regulation, but not in explicit regulation. Furthermore, naltrexone appeared to diminish activity in task-positive regions in response to emotional faces. These findings are consistent with a model where endogenous opioids 'fine-tune' affective responses to both negative and positive stimuli. Future research should explore dose–response effects, kappa-opioid contributions and whether similar results are seen in clinical populations. [ABSTRACT FROM AUTHOR]
Copyright of British Journal of Psychiatry is the property of Cambridge University Press and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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DbLabel: Psychology and Behavioral Sciences Collection
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PubType: Academic Journal
PubTypeId: academicJournal
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  Label: Title
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  Data: Effects of opioid antagonism on functional MRI correlates of explicit and implicit threat processing in healthy volunteers.
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  Data: <searchLink fieldCode="AR" term="%22Huneke%2C+Nathan+T%2E+M%2E%22">Huneke, Nathan T. M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22van+Steenbergen%2C+Henk%22">van Steenbergen, Henk</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fagan%2C+Harry+A%2E%22">Fagan, Harry A.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Molteni%2C+Laura%22">Molteni, Laura</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Midveris%2C+Algirdas%22">Midveris, Algirdas</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Phillips%2C+Naomi%22">Phillips, Naomi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Darekar%2C+Angela%22">Darekar, Angela</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22van+der+Wee%2C+Nic+J%2E+A%2E%22">van der Wee, Nic J. A.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Garner%2C+Matthew%22">Garner, Matthew</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Baldwin%2C+David+S%2E%22">Baldwin, David S.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22British+Journal+of+Psychiatry%22">British Journal of Psychiatry</searchLink>. Jun2026, Vol. 228 Issue 6, p530-538. 9p.
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  Data: <searchLink fieldCode="DE" term="%22Naltrexone%22">Naltrexone</searchLink><br /><searchLink fieldCode="DE" term="%22Functional+magnetic+resonance+imaging%22">Functional magnetic resonance imaging</searchLink><br /><searchLink fieldCode="DE" term="%22Emotion+regulation%22">Emotion regulation</searchLink><br /><searchLink fieldCode="DE" term="%22Control+%28Psychology%29%22">Control (Psychology)</searchLink><br /><searchLink fieldCode="DE" term="%22Threat+%28Psychology%29%22">Threat (Psychology)</searchLink><br /><searchLink fieldCode="DE" term="%22Human+research+subjects%22">Human research subjects</searchLink><br /><searchLink fieldCode="DE" term="%22Opioids%22">Opioids</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: We need to identify novel, tractable therapeutic targets for anxiety disorders. Converging evidence suggests the endogenous opioid system plays a role in modulating affective processing, but its contribution to regulation of threat processing in humans remains unclear. Aims: We investigated the neural correlates of non-specific opioid antagonism on explicit and implicit regulation of threatening stimuli in healthy volunteers, using functional magnetic resonance imaging (fMRI). Method: In a randomised, double-blind, placebo-controlled, crossover design, 38 healthy participants received the opioid antagonist naltrexone (50 mg) or placebo before completing two tasks during fMRI: (a) a cognitive emotional reappraisal task probing explicit regulation and (b) a face-viewing task probing implicit processing. Results: Contrary to our hypothesis, we found naltrexone reduced distress ratings during the reappraisal task (p = 0.044) without impairing regulation success. Explicit regulation in the reappraisal task engaged lateral prefrontal regions similarly across drug conditions. However, naltrexone attenuated ventromedial prefrontal cortex, thalamus and caudate activation when viewing negative images. Naltrexone additionally altered ventromedial prefrontal cortex activity and in task-positive regions including right premotor area and frontal pole compared with placebo when viewing emotional faces. In particular, naltrexone increased left middle frontal gyrus activity when viewing fearful faces. Conclusions: Our results support a role for opioid signalling in automatic emotional regulation, but not in explicit regulation. Furthermore, naltrexone appeared to diminish activity in task-positive regions in response to emotional faces. These findings are consistent with a model where endogenous opioids 'fine-tune' affective responses to both negative and positive stimuli. Future research should explore dose–response effects, kappa-opioid contributions and whether similar results are seen in clinical populations. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of British Journal of Psychiatry is the property of Cambridge University Press and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1192/bjp.2026.10605
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      – Code: eng
        Text: English
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        PageCount: 9
        StartPage: 530
    Subjects:
      – SubjectFull: Naltrexone
        Type: general
      – SubjectFull: Functional magnetic resonance imaging
        Type: general
      – SubjectFull: Emotion regulation
        Type: general
      – SubjectFull: Control (Psychology)
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      – SubjectFull: Threat (Psychology)
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      – SubjectFull: Human research subjects
        Type: general
      – SubjectFull: Opioids
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    Titles:
      – TitleFull: Effects of opioid antagonism on functional MRI correlates of explicit and implicit threat processing in healthy volunteers.
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              M: 06
              Text: Jun2026
              Type: published
              Y: 2026
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