Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers
Open accessAbstract
Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [(11)C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [(11)C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [(11)C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [(11)C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions.
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Blunted euphoria and response in opioid systems thought to be involved in 'liking' has been reported in individuals with gambling problems.
“Similar findings suggesting blunted euphoria and response in opioid systems thought to be involved in ‘liking’ has been reported in individuals with gambling problems (Mick et al., 2016).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Mick et al., 2016
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“Similar findings suggesting blunted euphoria and response in opioid systems thought to be involved in Bliking^ has been reported in individuals with gambling problems (Mick et al., 2016).”
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- Authors
- Mick, I., Myers, J., Ramos, A. C., Stokes, P. R. A., Erritzoe, D., Colasanti, A., Gunn, R. N., Rabiner, E. A., Searle, G. E., Waldman, A. D., Parkin, M. C., Brailsford, A. D., Galduróz, J. C. F., Bowden-Jones, H., Clark, L., Nutt, D. J., & Lingford-Hughes, A. R.
- Affiliations
- Imperial College London (GB)
- King's College London (GB)
- Universidade Federal de São Paulo (BR)
- University of British Columbia (CA)
- Corresponding author
- Lingford-Hughes, Anne R
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2015-11-10
- Volume
- 41
- Issue
- 7
- Pages
- 1742-1750
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4869041
- OpenAlex
- W2205787010
- Cited by
- 112
- References
- 54
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 8 · 2022: 2 · 2021: 5 · 2020: 49 · 2019: 8 · 2018: 15 · 2017: 8 · 2016: 8 · 2014: 1
- FWCI
- 12.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuropsychopharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, other-oa)
- Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- National Institute for Health and Care Research (ACF-2013-21-501, CL-2013-17-003)
- NIHR Imperial Biomedical Research Centre
- Topics
- Social Sciences › Psychology › Clinical Psychology › Gambling Behavior and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- gambling addiction, endogenous opioid release, amphetamine challenge, impulsivity, caudate nucleus, behavioral addiction, euphoria, alertness
- MeSH terms
- Administration, Oral, Adult, Amphetamine, Central Nervous System Stimulants, Analgesics, Opioid, Analysis of Variance, Carbon Isotopes, Female, Fentanyl, Gambling, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Positron-Emission Tomography
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