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Cited by 20Neurotransmitter Receptor Influence on BehaviorSubstance Abuse Treatment and OutcomesOpioid Use Disorder Treatment

A Review of DNA Risk Alleles to Determine Epigenetic Repair of mRNA Expression to Prove Therapeutic Effectiveness in Reward Deficiency Syndrome (RDS): Embracing “Precision Behavioral Management”

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Blum, Kenneth, Steinberg, Bruce, Gondré-Lewis, Marjorie C, Baron, David, Modestino, Edward J, Badgaiyan, Rajendra D, Downs, B William, Bagchi, Debasis +4 more·2021·Psychology Research and Behavior Management
DOI 10.2147/prbm.s292958PMC PMC8691196
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Abstract

This is a review of research on "Precision Behavioral Management" of substance use disorder (SUD). America is experiencing a high prevalence of substance use disorder, primarily involving legal and illegal opioid use. A 3000% increase in treatment for substance abuse has occurred between 2000 and 2016. Unfortunately, present day treatment of opioid abuse involves providing replacement therapy with powerful opioids to, at best, induce harm reduction, not prophylaxis. These interventions do not enhance gene expression and restore the balance of the brain reward system's neurotransmitters. We are proposing a generalized approach called "Precision Behavioral Management". This approach includes 1) using the Genetic Addiction Risk Severity (GARS, a 10 candidate polymorphic gene panel shown to predict ASI-alcohol and drug severity) to assess early pre-disposition to substance use disorder; 2) using a validated reward deficiency syndrome (RDS) questionnaire; 3) utilization of the Comprehensive Analysis of Reported Drugs (CARD™) to assess treatment compliance and abstinence from illicit drugs during treatment, and, importantly; 4) utilization of a "Pro-dopamine regulator (KB220)" (via IV or oral [KB220Z] delivery systems) to optimize gene expression, restore the balance of the Brain Reward Cascade's neurotransmitter systems and prevent relapse by induction of dopamine homeostasis, and; 5) utilization of targeted DNA polymorphic reward genes to direct mRNA genetic expression profiling during the treatment process. Incorporation of these events can be applied to not only the under-considered African-American RDS community, but all victims of RDS, as a demonstration of a paradigm shift that uniquely provides a novel putative "standard of care" based on DNA guided precision nutrition therapy to induce "dopamine homeostasis" and rebalance neurotransmitters in the Brain Reward Cascade. We are also developing a Reward Deficiency Syndrome Diagnostic Criteria (RDSDC) to assist in potential tertiary treatment.

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  • Recognizing the neurobiological underpinnings of loneliness could inform new treatment pathways.

    “Recognizing the neurobiological underpinnings of loneliness could inform new treatment pathways.”

    From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [80]

    The Introduction mentions social isolation only as a possible contributor to opioid overdoses. The Pro-Dopamine Regulator section discusses neural mechanisms and treatment approaches for reward deficiency syndrome and substance use disorder, not loneliness. Searches for loneliness and social isolation found no passage connecting loneliness’s neurobiology to new treatments; page numbers were unavailable in our copy. (LLM, conf=0.76)

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Research works printed but not linked: 8

  1. [32]Blum K, Chen AL, Oscar-Berman M, et al. Generational association studies of dopaminergic genes in reward deficiency syndrome (RDS) subjects: Selecting appropriate phenotypes for reward dependence behaviors. Int J Environ Res Public Health. 2011; 8(12): 4425– 4459. doi: 10.3390/ijerph8124425o 22408582 PMC3290972 · DOI
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  3. [55]Blum K, Madigan MA, Fried L, et al. Coupling Genetic Addiction Risk Score (GARS) and pro dopamine regulation (KB220) to combat substance use disorder (SUD). Glob J Addict Rehabilit Med. 2017; 1(2): 25– 34. doi: 10.19080/GJARM.2017.01.55556 PMC5796781 29399668 · DOI
  4. [104]Blum K, Chen ALC, Chen TJH, et al. Putative targeting of Dopamine D2 receptor function in Reward Deficiency Syndrome (RDS) by Synaptamine Complex™ Variant (KB220): clinical trial showing anti-anxiety effects. Gene Ther Mol Bio. 2009; 13: 214– 230.
  5. [117]Levy JE, Kunitz SJ. Indian Drinking: Navajo Practice and Anglo-American Theories. New York: Wiley; 1974.
  6. [125]Reuss CV, Kalava A, King KC. Prescription of Controlled Substances: benefits and Risks. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021. PMID: 30726003. 30726003
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  8. [134]Chapman EC, Ettiene E, Ofoegbu A, et al. The impact of pharmacogenetic testing on buprenorphine dosing in an African-American population. Second International Conference on Addiction Medicine and Reward Deficiency Syndrome. March 17–19; 2017; Baltimore, MD.

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Authors
Blum, K., Steinberg, B., Gondré-Lewis, M. C., Baron, D., Modestino, E. J., Badgaiyan, R. D., Downs, B. W., Bagchi, D., Brewer, R., McLaughlin, T., Bowirrat, A., & Gold, M.
Affiliations
  • Eötvös Loránd University (HU)
  • Curry College (US)
  • Howard University (US)
  • Western University of Health Sciences (US)
  • The University of Texas at San Antonio Health Science Center (US)
  • Ariel University (IL)
  • Washington University in St. Louis (US)
Corresponding author
Steinberg, Bruce
ORCID
Venue
Psychology Research and Behavior Management
Publisher
Informa UK Limited
Published
2021-12
Volume
Volume 14
Pages
2115-2134
ISSN
1179-1578 (ISSN-L)
DOI
10.2147/prbm.s292958
PMC
PMC8691196
OpenAlex
W4200199493
Cited by
20
References
118
Citations by year
2026: 2 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 7
FWCI
0.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychology Research and Behavior Management (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc)
Funders
  • National Institutes of Health
  • National Institute on Minority Health and Health Disparities (R41MD012318, U54MD007597)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Keywords
reward deficiency syndrome, substance use disorders, mRNA expression profiling, dopamine homeostasis, brain reward system, opioid use disorder, relapse prevention, African American patients, medication adherence

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