Genetic addiction risk score GARS trade a predictor of vulnerability to opioid dependence
Abstract
The interaction of neurotransmitters and genes that control the release of dopamine is the Brain Reward Cascade (BRC). Variations within the BRC, whether genetic or epigenetic, may predispose individuals to addictive behaviors and altered pain tolerance. This discussion authored by a group of concerned scientists and clinicians examines the Genetic Addiction Risk Score (GARS), the first test to accurately predict vulnerability to pain, addiction, and other compulsive behaviors, defined as Reward Deficiency Syndrome (RDS). Innovative strategies to combat epidemic opioid, iatrogenic prescription drug abuse and death, based on the role of dopaminergic tone in pain pathways, are proposed. Sensitivity to pain may reside in the mesolimbic projection system, where genetic polymorphisms associate with a predisposition to pain vulnerability or tolerance. They provide unique therapeutic targets that could assist in the treatment of pain, and identify risk for subsequent addiction. Pharmacogenomic testing of candidate genes like CB1, mu receptors, and PENK might result in pharmacogenomic, personalized solutions, and improved clinical outcomes. Genetically identifying risk for all RDS behaviors, especially in compromised populations, may be a frontline tool to assist municipalities to provide better resource allocation.
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These genetic insights point to new therapeutic targets for pain management and addiction prevention and recovery.
“These genetic insights point to new therapeutic targets for pain management and addiction prevention and recovery.26,28–32”
From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [26]
The Reward Deficiency Syndrome (RDS) Consortium has proposed novel strategies for addressing the opioid crisis, particularly iatrogenic addiction, by targeting dopaminergic tone in pain processing pathways.
“The Reward Deficiency Syndrome (RDS) Consortium has proposed novel strategies for addressing the opioid crisis, particularly iatrogenic addiction, by targeting dopaminergic tone in pain processing pathways.26”
From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [26]
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Quiñones, C., & Griffiths, M. D. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108632591.028 · Cited by 1 · see citing works
Compton, W. M., & Blanco, C. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108632591.001
Novel Psychoactive Substances: A New Challenge for Prevention and Treatment
Kapitány‐Fövény, M., Corazza, O., Marrinan, S., & Demetrovics, Z. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108632591.032
Human Laboratory Paradigms in Addictions Research
Morris, V. L., Arshad, F., Balodis, I. M., Reed, D. D., MacKillop, J. M., & Amlung, M. T. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108632591.010
Anhedonia in Addictive Behaviors
Dyer, W. G., Leventhal, A. M., Goldenson, N. I., & Bello, M. S. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108632591.039
American Legal Issues in Addiction Treatment and Research
Willick, D. H. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108632591.041
Strack, R. W., Orsini, M. M., Ewald, D. R., & Scheier, L. M. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108632591.019
Clinical and Research Methods in the Addictions
Sussman, S. Y. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108632591.008
Levels of Analysis and Etiology
(2020) · Cambridge University Press eBooks · doi:10.1017/9781108632591.014
Ongoing and Future Research Directions
(2020) · Cambridge University Press eBooks · doi:10.1017/9781108632591.030
Sussman, S. Y. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108632591.002
Srivastava, A. B., & Gold, M. S. (2020) · Cambridge University Press eBooks · doi:10.1017/9781108632591.033
- Authors
- Blum, K.
- Affiliations
- University of Florida Health (US)
- Corresponding author
- Blum, Kenneth
- ORCID
- Blum, Kenneth
- Venue
- Frontiers in Bioscience
- Publisher
- IMR Press
- Published
- 2018
- Volume
- 10
- Issue
- 1
- Pages
- 175-196
- ISSN
- 1944-7892 (ISSN-L)
- 1945-0494
- 1945-0508
- DOI
- 10.2741/e816
- OpenAlex
- W2758983729
- Cited by
- 104
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 3 · 2022: 11 · 2021: 9 · 2020: 50 · 2019: 12 · 2018: 5
- FWCI
- 8.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Frontiers in Bioscience-Elite (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centers for Disease Control and Prevention
- National Institute on Minority Health and Health Disparities (R41MD012318, G12MD007597)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Keywords
- opioid use disorder, reward deficiency syndrome, dopamine, pain sensitivity, mesolimbic system, genetic polymorphism, pharmacogenomics, CB1 receptor, mu-opioid receptor, proenkephalin, prescription drug misuse, addiction risk prediction, personalized pain treatment
- MeSH terms
- Analgesics, Opioid, Dopamine, Humans, Opioid-Related Disorders, Pain, Pharmacogenetics, Stress, Psychological, Genetic Predisposition to Disease, Pain Management
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