Focusing on the Opioid System for Addiction Biomarker Discovery
Abstract
Substance use disorders (SUD) and behavioral addictions are devastating conditions that impose a severe burden on all societies, and represent difficult challenges for clinicians. Therefore, biomarkers are urgently needed to help predict vulnerability, clinical course, and response to treatment. Here, we elaborate on the potential for addiction biomarker discovery of the opioid system, particularly within the emerging framework aiming to probe opioid function in peripheral tissues. Mu, delta, and kappa opioid receptors all critically regulate neurobiological and behavioral processes that define addiction, and are also targeted by major pharmacotherapies used in the management of patients with SUD. We propose that opioid biomarkers may have the potential to improve and guide diagnosis and therapeutic decisions in the addiction field.
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Methylation at the mu-opioid receptor (MOR) gene is most strongly associated with drug addiction as well as incentive motivation for processed food.
“While methylation at the mu-opioid receptor (MOR) gene is most strongly associated with drug addiction [144] as well as incentive motivation for processed food [145,146], decreased methylation at the kappa-opioid receptor (KOR) in the anterior insula has been shown in child abuse [147] (discussed further in Section 4.1).”
From Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications (2020) · cites this paper as [144]
Reduced MOR has been observed in comorbid binge eating disorder and obesity and across SUDs.
“Meanwhile, reduced MOR has been observed in comorbid binge eating disorder and obesity [191] and across SUDs [144] which strongly suggest neurochemical overlap in these conditions, and which can persist despite weight loss or periods of drug abstinence.”
From Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications (2020) · cites this paper as [144]
Reduced MOR across binge eating disorder, obesity, and SUDs strongly suggests neurochemical overlap in these conditions, and this can persist despite weight loss or periods of drug abstinence.
“Meanwhile, reduced MOR has been observed in comorbid binge eating disorder and obesity [191] and across SUDs [144] which strongly suggest neurochemical overlap in these conditions, and which can persist despite weight loss or periods of drug abstinence.”
From Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications (2020) · cites this paper as [144]
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Endogenous Opiates and Behavior: 2015
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OPRM1 gene variants modulate amphetamine-induced euphoria in humans
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Opioids and skin homeostasis, regeneration and ageing – What's the evidence?
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RSK2 Signaling in Medial Habenula Contributes to Acute Morphine Analgesia
Darcq, E., Befort, K., Koebel, P., Pannetier, S., Mahoney, M. K., Gavériaux‐Ruff, C., Hanauer, A., & Kieffer, B. L. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.316 · Cited by 37 · see citing works
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Naltrexone ameliorates functional network abnormalities in alcohol‐dependent individuals
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Using iPSC‐derived human DA neurons from opioid‐dependent subjects to study dopamine dynamics
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Morphine‐induced mu opioid receptor trafficking enhances reward yet prevents compulsive drug use
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Meta-Analyses of Genome-Wide Association Data Hold New Promise for Addiction Genetics
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Compulsive use of dopamine replacement therapy: a model for stimulant drug addiction?
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Alteration of lymphocyte opioid receptors in methadone maintenance subjects
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Combined Whole Methylome and Genomewide Association Study ImplicatesCNTN4in Alcohol Use
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A gene-by-sex interaction for nicotine reward: evidence from humanized mice and epidemiology
Bernardi, R. E., Zohsel, K., Hirth, N., Treutlein, J., Heilig, M. A., Laucht, M., Spanagel, R., & Sommer, W. H. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.132 · Cited by 17 · see citing works
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Complexities of the Mu Opioid Receptor
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Opioid receptors: drivers to addiction?
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The impact of sugar consumption on stress driven, emotional and addictive behaviors
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The Opioid Crisis and the Future of Addiction and Pain Therapeutics
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The opioid system and the social brain: implications for depression and suicide
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Diagnosis of Early opioids addiction by label-free serum SERS fingerprints with machine learning
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An association study between methamphetamine use disorder with psychosis and polymorphisms in MiRNA
Sun, Q., Zhao, Y. F., Zhang, K., Su, H., Chen, T., Jiang, H., Du, J., Zhong, N., Yu, S., & Zhao, M. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134725 · Cited by 12 · see citing works
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An electroencephalogram biomarker of fentanyl drug effects
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Opioid use disorder research and the Council for the Advancement of Nursing Science priority areas
Eckardt, P. A., Bailey, D. E., DeVon, H. A., Dougherty, C. M., Ginex, P., Krause‐Parello, C. A., Pickler, R. H., Richmond, T. S., Rivera, E., Roye, C. F., et al. (2020) · Nursing Outlook · doi:10.1016/j.outlook.2020.02.001 · Cited by 4 · see citing works
Recent Advances in Biomarkers of Addiction: A Narrative Review
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Sex-divergent brain epigenetic reprogramming by chronic opioidsPreprint
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Potential Involvement of Apelin/APJ System in Addiction and Neuroprotection Against Drugs of Abuse
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Lutz, P.-É., Lalanne, L., Caparros-Roissard, A., Waeckerle, G., Scherer, C., Lebreton, M., Audran, M., Merah, I., Chappuy, M., Avril, E., et al. (2025) · Psychotropes · doi:10.3917/psyt.312.0097
Sex differences in functional genomic mechanisms of opioid action
Falconnier, C. (2023) · theses.fr (ABES) · doi:10.70675/3a582f0az7be5z4cefzb85fz594ba4d910cd
Système opioïde et cerveau social : implication dans la dépression et le suicide
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- Authors
- Belzeaux, R., Lalanne, L., Kieffer, B. L., & Lutz, P.-E.
- Affiliations
- Inserm (FR)
- Douglas Mental Health University Institute (CA)
- Venue
- Trends in Molecular Medicine
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 24
- Issue
- 2
- Pages
- 206-220
- ISSN
- 1471-4914 (ISSN-L)
- OpenAlex
- W2785235690
- Cited by
- 28
- References
- 119
- Citations by year
- 2025: 6 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 5 · 2018: 4
- FWCI
- 0.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Fondation FondaMental
- Fondation Fyssen
- Fondation Bettencourt-Schueller
- Canadian Institutes of Health Research
- American Foundation of Suicide Prevention
- Fondation pour la Recherche Médicale
- Fondation Deniker
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- opioid system, addiction biomarkers, substance use disorders, behavioral addiction, mu-opioid receptor, delta opioid receptor, kappa opioid receptor, opioid therapy, addiction diagnosis, treatment response prediction
- MeSH terms
- Humans, Receptors, Opioid, Biomarkers, Behavior, Addictive, Substance-Related Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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