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Summary Document Research on RDS Anti-addiction Modeling: Annotated Bibliography

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Kenneth Blum, David A. Baron, Thomas McLaughlin, Panayotis K. Thanos, Catherine A. Dennen, Mauro Ceccanti, Eric R. Braverman, Alireza Sharafshah +3 more·2024·Journal of Addiction Psychiatry
DOI 10.17756/jap.2024-043PMC PMC11100022
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Abstract

Annotated bibliography of genetic addiction risk severity (GARS) publications, pro-dopamine regulation in nutraceuticals (KB220 nutraceutical variants), and policy documents. Further research is required to encourage the field to consider "Reward Deficiency Syndrome (RDS) Anti-addiction Modeling" which involves early risk identification by means of genetic assessment similar to GARS, followed by induction of dopamine homeostasis by means of genetically guided pro-dopamine regulation similar to KB220. These results suggest that genetically based treatments may be a missing piece in the treatment of substance use disorder (SUD).

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  • An enrichment analysis of 59 key genes revealed significant associations with dopaminergic pathways in the BRC, offering strong support for using GARS as a predictive tool.

    “An enrichment analysis of 59 key genes revealed significant associations with dopaminergic pathways in the BRC, offering strong support for using GARS as a predictive tool.”

    From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [21]

    The sections “GARS™ as a predictor of SUD” and “GARS, a predictor of vulnerability to opioid dependence” describe GARS as a potential risk-prediction tool and link addiction risk to dopamine-related brain reward circuitry (pages unavailable). However, our copy does not report an enrichment analysis of 59 key genes or establish that such an analysis provides strong support for GARS. Searches for “59 key genes,” “enrichment analysis of 59,” and “59 genes” did not locate that result. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The Genetic Addiction Risk Severity test can identify at-risk individuals, enabling precision-targeted interventions.

    “The Genetic Addiction Risk Severity test can identify at-risk individuals, enabling precision-targeted interventions.”

    From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [21]

  • GARS may assist in early identification of addiction vulnerability, guide personalized pharmacotherapy (including for pain management), and improve prescription drug safety.

    “This test may assist in early identification of addiction vulnerability, guide personalized pharmacotherapy (including for pain management), and improve prescription drug safety.21”

    From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [21]

  • Findings from Blum et al.'s work, centered around the Brain Reward Cascade (BRC), suggest that RDS may represent a primary phenotype, with various behavioral disorders acting as endophenotypes influenced by specific genetic variants.

    “Findings from this work, centered around the Brain Reward Cascade (BRC), suggest that RDS may represent a primary phenotype, with various behavioral disorders acting as endophenotypes influenced by specific genetic variants.”

    From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [21]

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Research works printed but not linked: 107

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  80. McLaughlin T, Blum K, Steinberg B, Modestino EJ, Fried L, et al. 2018. Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD. J Behav Addict 7(1): 192-203. 10.1556/2006.6.2017.081 [PubMed: 29316800] · DOI
  81. Blum K, Whitney D, Fried L, Febo M, Waite RL, et al. 2016. Hypothesizing that a pro- dopaminergic regulator (KB220Z ™ liquid variant) can induce "dopamine homeostasis" and provide adjunctive detoxification benefits in opiate/opioid dependence. Clin Med Rev Case Rep 3(8): 125. 10.23937/2378-3656/1410125 [PubMed: 29034323] · DOI
  82. McLaughlin T, Han D, Nicholson J, Steinberg B, Blum K, et al. 2017. Improvement of long-term memory access with a pro-dopamine regulator in an elderly male: are we targeting dopamine tone? J Syst Integr Neurosci 3(3): 1-7. 10.15761/JSIN.1000165 · DOI
  83. McLaughlin T, Blum K, Oscar-Berman M, Febo M, Agan G, et al. 2015. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: role of enhanced brain reward functional connectivity and homeostasis redeeming joy. J Behav Addict 4(2): 106-115. 10.1556/2006.4.2015.008 [PubMed: 26132915] · DOI
  84. Blum K, Liu Y, Wang W, Wang Y, Zhang Y, et al. 2015. rsfMRI effects of KB220Z ™ on neural pathways in reward circuitry of abstinent genotyped heroin addicts. Postgrad Med 127(2): 232- 241. 10.1080/00325481.2015.994879 [PubMed: 25526228] · DOI
  85. Blum K, Chen TJ, Morse S, Giordano J, Chen ALC, et al. 2010. Overcoming qEEG abnormalities and reward gene deficits during protracted abstinence in male psychostimulant and polydrug abusers utilizing putative dopamine D2 agonist therapy: part 2. Postgrad Med 122(6): 214-226. 10.3810/pgm.2010.11.2237 [PubMed: 21084796] · DOI
  86. McLaughlin T, Febo M, Badgaiyan RD, Barh D, Dushaj K, et al. 2016. KB220Z ™ a pro-dopamine regulator associated with the protracted, alleviation of terrifying lucid dreams. Can we infer neuroplasticity-induced changes in the reward circuit? J Reward Defic Syndr Addict Sci 2(1): 3-13. [PubMed: 28210713]
  87. Mclaughlin T, Oscar-Berman M, Simpatico T, Giordano J, Jones S, et al. 2013. Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette's syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic amino-acid therapy (NAAT). J Behav Addict 2(2): 117-124. 10.1556/JBA.2.2013.2.8 [PubMed: 26165932] · DOI
  88. Steinberg B, Blum K, McLaughlin T, Lubar J, Febo M, et al. 2016. Low-resolution electromagnetic tomography (LORETA) of changed brain function provoked by pro-dopamine regulator (KB220z) in one adult ADHD case. Open J Clin Med Case Rep 2(11): 1121. [PubMed: 27610420]
  89. Blum K, Marcelo F, Dushaj K, Fried L, Badgaiyan RD. 2016. "Pro-dopamine regulation (KB220Z ™ )" as a long-term therapeutic modality to overcome reduced resting state dopamine tone in opiate/opioid epidemic in America. J Syst Integr Neurosci 2(3): 162-165. 10.15761/ JSIN.1000129 [PubMed: 28491463] · DOI
  90. Modestino EJ, Blum K, Oscar-Berman M, Gold MS, Duane DD, et al. 2015. Reward deficiency syndrome: attentional/arousal subtypes, limitations of current diagnostic nosology, and future research. J Reward Defic Syndr 1(1): 6. [PubMed: 26306327]
  91. Blum K, Chen TJ, Bailey J, Bowirrat A, Femino J, et al. 2011. Can the chronic administration of the combination of buprenorphine and naloxone block dopaminergic activity causing anti- reward and relapse potential? Mol Neurobiol 44: 250-268. 10.1007/s12035-011-8206-0 [PubMed: 21948099] · DOI
  92. Blum K, Briggs AH, Trachtenberg MC, Delallo L, Wallace JE. 1987. Enkephalinase inhibition: regulation of ethanol intake in genetically predisposed mice. Alcohol 4(6): 449-456. 10.1016/0741-8329(87)90084-x [PubMed: 2829941] · DOI
  93. Blum K, Calhoun W, Merritt J, Wallace JE. 1973. L-DOPA: effect on ethanol narcosis and brain biogenic amines in mice. Nature 242(5397): 407-409. 10.1038/242407a0 [PubMed: 4735636] 100. · DOI
  94. Blum K, Trachtenberg MC, Ramsay JC. 1988. Improvement of inpatient treatment of the alcoholic as a function of neurotransmitter restoration: a pilot study. Int J Addict 23(9): 991-998. 10.3109/10826088809058853 [PubMed: 2906910] 101. · DOI
  95. Blum K, Trachtenberg MC, Elliott CE, Dingler ML, Sexton RL, et al. 1988. Enkephalinase inhibition and precursor amino acid loading improves inpatient treatment of alcohol and polydrug abusers: double-blind placebo-controlled study of the nutritional adjunct SAAVE ™ . Alcohol 5(6): 481-493. 10.1016/0741-8329(88)90087-0 [PubMed: 3072969] 102. · DOI
  96. Blum K, Allison D, Trachtenberg MC, Williams RW. 1988. Reduction of both drug hunger and withdrawal against advice rate of cocaine abusers in a 30-day inpatient treatment program by the neuronutrient Tropamine. Curr Ther Res 43(6): 1204-1214. 103. Brown RJ, Blum K, Trachtenberg MC. 1990. Neurodynamics of relapse prevention: a neuronutrient approach to outpatient DUI offenders. J Psychoactive Drugs 22(2): 173-187. 10.1080/02791072.1990.10472542 [PubMed: 2374070] 104. · DOI
  97. Blum K, Trachtenberg MC, Cook DW. 1990. Neuronutrient effects on weight loss in carbohydrate bingers: an open clinical trial. Curr Ther Res 48(2): 217-233. 105.
  98. DeFrance JF, Hymel C, Trachtenberg MC, Ginsberg LD, Schweitzer FC, et al. 1997. Enhancement of attention processing by Kantroll ™ in healthy humans: a pilot study. Clin Electroencephalogr 28(2): 68-75. 10.1177/155005949702800204 [PubMed: 9137870] 106. Cold JA. 1996. NeuRecover-SATM in the treatment of cocaine withdrawal and craving: a pilot study. Clin Drug Invest 12(1): 1-5. 107. Ross J 2001. Amino-acid precursor and enkephalinase inhibition therapy: evidence for effectiveness in treatment of "reward deficiency syndrome (RDS)" with particular emphasis on eating disorders. Mol Psychiatry 6(Suppl 1): S1-S8. [PubMed: 11247387] 108. Chen TJ, Blum K, Waite RL, Meshkin B, Schoolfield J, et al. 2007. Gene\Narcotic Attenuation Program attenuates substance use disorder, a clinical subtype of reward deficiency syndrome. Adv Ther 24: 402-414. 10.1007/BF02849910 [PubMed: 17565932] 109. Chen TJ, Blum K, Payte JT, Schoolfield J, Hopper D, et al. 2004. Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN-10, amino-acid precursors and enkephalinase inhibition therapy. Med Hypotheses 63(3): 538-548. 10.1016/ j.mehy.2004.02.051 [PubMed: 15288384] 110. · DOI
  99. Blum K, Chen TJ, Williams L, Chen AL, Downs WB, et al. 2008. A short term pilot open label study to evaluate efficacy and safety of LG839, a customized DNA directed nutraceutical in obesity: exploring Nutrigenomics. Gene Ther Mol Biol 12(2): 371-382. 111. Blum K, Chen TJ, Downs BW, Meshkin B, Blum SH, et al. 2007. Synaptamine (SG8839) an amino-acid enkephalinase inhibition nutraceutical improves recovery of alcoholics, a subtype of reward deficiency syndrome (RDS). Trends Appl Sci Res 2(2): 132-138. 112. Chen TJ, Blum K, Kaats G, Braverman ER, Eisenberg A, et al. 2007. Chromium picolinate (CrP) a putative anti-obesity nutrient induces changes in body composition as a function of Taq1 dopamine D2 receptor polymorphisms in a randomized double-blind placebo controlled study. Gene Ther Mol Biol 11: 161-170. 113.
  100. Blum K, Chen AL, Chen TJ, Rhoades P, Prihoda TJ, et al. 2008. LG839: anti-obesity effects and polymorphic gene correlates of reward deficiency syndrome. Adv Ther 25: 894-913. 10.1007/ s12325-008-0093-z [PubMed: 18781289] 114. · DOI
  101. Blum K, Modestino EJ, Lott L, Siwicki D, Baron D, et al. 2018. Introducing "precision addiction management (PAM ® )" as an adjunctive genetic guided therapy for abusable drugs in America. Open Access J Behav Sci Psychol 1(2): 1-4. [PubMed: 30662982] 119.
  102. Blum K, Han D, Modestino EJ, Saunders S, Roy III AK, et al. 2018. A systematic, intensive statistical investigation of data from the comprehensive analysis of reported drugs (CARD) for compliance and illicit opioid abstinence in substance addiction treatment with buprenorphine/naloxone. Subst Use Misuse 53(2): 220-229. 10.1080/10826084.2017.1400064 [PubMed: 29257919] 122. · DOI
  103. Blum K, Han D, Femino J, Smith DE, Saunders S, et al. 2014. Systematic evaluation of "compliance" to prescribed treatment medications and "abstinence" from psychoactive drug abuse in chemical dependence programs: data from the comprehensive analysis of reported drugs. PLoS One 9(9): e104275. 10.1371/journal.pone.0104275 [PubMed: 25247439] 123. · DOI
  104. Blum K, Gold M, Clark HW, Dushaj K, Badgaiyan RD. 2016. Should the united states government repeal restrictions on buprenorphine/naloxone treatment? Subst Use Misuse 51(12): 1674-1679. 10.1080/10826084.2016.1200097 [PubMed: 27462930] 124. · DOI
  105. Hill E, Han D, Dumouchel P, Dehak N, Quatieri T, et al. 2013. Long term Suboxone ™ emotional reactivity as measured by automatic detection in speech. PLoS One 8(7): e69043. 10.1371/ journal.pone.0069043 [PubMed: 23874860] 125. · DOI
  106. Blum K, Oscar-Berman M, Jacobs W, McLaughlin T, Gold MS. 2014. Buprenorphine response as a function of neurogenetic polymorphic antecedents: can dopamine genes affect clinical outcomes in reward deficiency syndrome (RDS)? J Addict Res Ther 5: 185. 10.4172/2155-6105.1000185 126. · DOI
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Cited by

Sorted by citations

Authors
Blum, K., Baron, D. A., McLaughlin, T., Thanos, P. K., Dennen, C. A., Ceccanti, M., Braverman, E. R., Sharafshah, A., Lewandrowski, K., Giordano, J., & Badgaiyan, R. D.
Affiliations
  • Western University of Health Sciences (US)
  • State University of New York (US)
  • Thomas Jefferson University (US)
  • Sapienza University of Rome (IT)
  • University of Isfahan (IR)
  • Fundación Universitaria Sanitas (CO)
  • Case Western Reserve University (US)
ORCID
Venue
Journal of Addiction Psychiatry
Publisher
United Scientific Group
Published
2024-04-05
Volume
8
Issue
1
Pages
1-33
ISSN
3065-5889 (ISSN-L)
DOI
10.17756/jap.2024-043
PMC
PMC11100022
OpenAlex
W4398156078
Cited by
11
References
7
Citations by year
2025: 5 · 2024: 3 · 2023: 2 · 2022: 1
FWCI
1.40
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Journal of Addiction Psychiatry (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
Funders
  • U.S. Department of Veterans Affairs (I01 CX000479)
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01NS073884)
  • National Institute on Minority Health and Health Disparities (R41MD012318)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Social Sciences › Psychology › Clinical Psychology › Gambling Behavior and Treatments
Keywords
reward deficiency syndrome, dopamine homeostasis, addiction treatment, genetic risk prediction

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