Acta Scientific Neurology (ASNE) (ISSN: 2582-1121)

Opinion Volume 4 Issue 2

Should We Embrace the Incorporation of Genetically Guided “Dopamine Homeostasis” in the Treatment of Reward Deficiency Syndrome (RSD) as a Frontline Therapeutic Modality?

Kenneth Blum1-3*, Ali Raza1, Tiffany Schultz1, Rehan Jalali1, Richard Green1, Raymond Brewer1, Panyotis K Thanos4, Thomas McLaughlin1, David Baron2, Abdalla Bowirrat5, Igor Elman6, B William Downs1, Debasis Bagchi1,7 and Rajendra D Badgaiyan8

1The Kenneth Blum Behavioral Neurogenetic Institute, Austin, Texas, USA
2Graduate College, Western University Health Sciences, Pomona, California, USA
3Division of Nutrigenomics, Center for Genomic Testing, Geneus Health, LLC., San Antonio, Texas, USA
4Department of Psychology, University of Buffalo, the State University of New York, Buffalo, NY, USA
5Department of Neuroscience and Genetics, Interdisciplinary Center Herzliya, Israel
6Department of Psychiatry, Harvard University College of Medicine, Cambridge, Massachusetts, USA
7Department of Pharmaceutical Sciences, South Texas University College of Pharmacy, Houston, Texas, USA
8Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, San Antonio, TX, Long School of Medicine, University of Texas Medical Center, San Antonio, TX, USA

*Corresponding Author: Kenneth Blum, The Kenneth Blum Behavioral Neurogenetic Institute, Austin, Texas, USA.

Received: December 26, 2020; Published: January 28, 2021



In 2019, the US Center for Disease Control and Prevention provided vital statistics related to drug overdoses in the United State1. They concluded that in the USA the number of deaths at almost 72,000 was due to 66.6% of opioid overdoses. In fact, the rate is alarming and increasing yearly. To make 2021 even more scary is the daunting effect on increased drug usage due to COVID 19 as a pandemic, albeit the new vaccines. Specifically, in 2020, the death rate from opioid overdoses rose to 13% nationally and in some sates 30%. The common neuromodulating aspects of neurotransmission, and its disruption via chronic exposure of drugs and behavioral addictions, requires further intense research focus on developing novel strategies to combat these unwanted genetic and epigenic infractions as accomplished with heroin addiction by our group. The take home message is the plausible acceptance of the well-established evidence for hypodopaminergia, a blunted reward processing system, reduced resting state functional connectivity, genetic antecedents, anti- reward symptomatology, poor compliance with MAT, and generalized RDS. With this evidence it is conceivable that pursuit through intensive future research should involve an approach that incorporates “dopamine homeostasis”. This required paradigm shift may consist of many beneficial modalities including but not limited to: exercise, pro-dopamine regulation, nutrigenomics, cognitive behavioral therapy, hedonic hot spot targets brain, rTMRS, deep brain stimulation, diet, genetic edits, genetic guided therapeutics, epigenetic repair, amongst others. It is our opinion that nutrigenomics may assist the millions of people of getting out of a” hypodopaminergic ditch” WC 250.

Keywords: Reward Deficiency Syndrome; Anti reward Symptomatology; Hypodopaminergia; Genetic Addiction Risk Severity (GARS) Testing; Dopamine Homeostasis



  1. Miller DK., et al. “Acute intravenous synaptamine complex variant KB220™ "normalizes" neurological dysregulation in patients during protracted abstinence from alcohol and opiates as observed using quantitative electroencephalographic and genetic analysis for reward polymorphisms: part 1, pilot study with 2 case reports”. Postgraduate Medical Journal 122.6 (2012): 188-213.
  2. Miller M., et al. “Early intervention of intravenous KB220IV--neuroadaptagen amino-acid therapy (NAAT) improves behavioral outcomes in a residential addiction treatment program: a pilot study”. Journal of Psychoactive Drugs 44.5 (2012): 398-409.
  3. Uys JD., et al. “Glutathione and redox signaling in substance abuse”. Biomed Pharmacotherapy 68.6 (2014): 799-807.
  4. Janicki PK and Lipkowski AW. “Kyotorphin and D-kyotorphin stimulate Met-enkephalin release from rat striatum in vitro”. Neuroscience Letter 43.1 (1983): 73-77.
  5. Witt EA and Reissner KJ. “The effects of nicotinamide on reinstatement to cocaine seeking in male and female Sprague Dawley rats”. Psychopharmacology (Berl) 237.3 (2020): 669-680.
  6. O'HOLLAREN P. “Diphosphopyridine nucleotide in the prevention, diagnosis and treatment of drug addiction. A preliminary report”. Western Journal of Surgery, Obstetrics, and Gynecology 69 (1961): 213-215.
  7. Blum K., et al. “In Search of Reward Deficiency Syndrome (RDS)-free Controls: The "Holy Grail" in Genetic Addiction Risk Testing”. Current Psychopharmacology 9.1 (2020): 7-21
  8. Fried L., et al. “Hypodopaminergia and "Precision Behavioral Management" (PBM): It is a Generational Family Affair”. Current Pharmaceutical Biotechnology 21.6 (2020): 528-541.
  9. Blum K., et al. “Introducing Precision Addiction Management of Reward Deficiency Syndrome, the Construct That Underpins All Addictive Behaviors”. Frontiers in Psychiatry 9 (2018): 548.
  10. Blum K., et al. “Genetic addiction risk score (GARS) ™, a predictor of vulnerability to opioid dependence”. Frontiers in Bioscience (Elite Ed) 10 (2018): 175-196.
  11. Blum K., et al. “Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse”. ECPP 7.8 (2018): 564-579.
  12. Lindgren E., et al. “Food addiction: A common neurobiological mechanism with drug abuse”. Frontiers in Bioscience (Landmark Ed) 23 (2018): 811-836.
  13. Solanki N., et al. “Administration of a putative pro-dopamine regulator, a neuronutrient, mitigates alcohol intake in alcohol-preferring rats”. Behavioural Brain Research 385 (2020): 112563.
  14. Blum K., et al. “Overcoming qEEG abnormalities and reward gene deficits during protracted abstinence in male psychostimulant and polydrug abusers utilizing putative dopamine D₂ agonist therapy: part”. Postgraduate Medical Journal 122.6 (2010): 214-226.
  15. Braverman ER., et al. “Substance use disorder exacerbates brain electrophysiological abnormalities in a psychiatrically-ill population”. Clinical Electroencephalography 27 (1996): 5-27.
  16. DeFrance JF., et al. “Enhancement of attention processing by Kantroll in healthy humans: a pilot study”. Clinical Electroencephalography 28.2 (1997): 68-75.
  17. Blum K., et al. “The benefits of genetic addiction risk score (GARS™) and pro-dopamine regulation in combating suicide in the American Indian population”. Journal of Systems and Integrative Neuroscience 4 (2018): 10.
  18. Vitali M., et al. “Neurophysiological Measures and Alcohol Use Disorder (AUD): Hypothesizing Links between Clinical Severity Index and Molecular Neurobiological Patterns”. Journal of Addiction Research and Therapy 5.2 (2016): 182.
  19. Blum K., et al. “Genetic Addiction Risk Score (GARS): molecular neurogenetic evidence for predisposition to Reward Deficiency Syndrome (RDS)”. Molecular Neurobiology 50.3 (2014): 765-796.
  20. Blum K., et al. “Critical Analysis of White House Anti-Drug Plan”. Global Journal of Addiction and Rehabilitation Medicine 1.4 (2017): 555568.
  21. Blum K., et al. “Neurogenetics of dopaminergic receptor supersensitivity in activation of brain reward circuitry and relapse: proposing "deprivation-amplification relapse therapy" (DART) ”. Postgraduate Medical Journal 121.6 (2009): 176-196.
  22. Blum K., et al. “Neuropsychiatric Genetics of Happiness, Friendships, and Politics: Hypothesizing Homophily ("Birds of a Feather Flock Together") as a Function of Reward Gene Polymorphisms”. Journal of Genetic Syndromes and Gene Therapy 3.112 (2012): 1000112.
  23. Blum K., et al. “Synaptamine (SG8839)TM, An Amino-Acid Enkephalinase Inhibition Nutraceutical Improves Recovery of Alcoholics, A Subtype of Reward Deficiency Syndrome (RDS)”. Trends in Applied Sciences Research 2.3 (2007): 132-138.
  24. Volkow ND and Morales M. “The Brain on Drugs: From Reward to Addiction”. Cell 162.4 (2015): 712-725.
  25. Blum K., et al. “Molecular neurological correlates of endorphinergic/dopaminergic mechanisms in reward circuitry linked to endorphinergic deficiency syndrome (EDS)”. Journal of the Neurological Sciences 411 (2020): 116733.
  26. Edwards D., et al. “Addiction by Any Other Name is Still Addiction: Embracing Molecular Neurogenetic/Epigenetic Basis of Reward Deficiency”. Journal of Addiction Science 6.1 (2020): 1-4.
  27. Blum K., et al. “Putative COVID- 19 Induction of Reward Deficiency Syndrome (RDS) and Associated Behavioral Addictions with Potential Concomitant Dopamine Depletion: Is COVID-19 Social Distancing a Double Edged Sword?” Substance Use and Misuse 55.14 (2020): 2438-2442.
  28. Downs BW., et al. “Molecular neuro-biological and systemic health benefits of achieving dopamine homeostasis in the face of a catastrophic pandemic (COVID- 19): A mechanistic exploration”. Journal of Systems and Integrative Neuroscience 7 (2020): 10.15761/JSIN.1000228.
  29. Blum K and Baron D. “Opioid Substitution Therapy: Achieving Harm Reduction While Searching for a Prophylactic Solution”. Current Pharmaceutical Biotechnology 20.3 (2019): 180-182.
  30. Downs BW., et al. “Death by Opioids: Are there non-addictive scientific solutions?”. Journal of Systems and Integrative Neuroscience (2019).
  31. Blum K., et al. “Pro-dopamine regulation (KB220Z™)" as a long-term therapeutic modality to overcome reduced resting state dopamine tone in opiate/opioid epidemic in America”. Journal of Systems and Integrative Neuroscience 2.3 (2016): 162-165.
  32. Larney S., et al. “A systematic review and meta-analysis of naltrexone implants for the treatment of opioid dependence”. Drug Alcohol Review 33.2 (2014): 115-128.
  33. Blum K., et al. “Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse”. ECPP 7.8 (2018): 564-579.
  34. Blum K., et al. “Withdrawal from Buprenorphine/Naloxone and Maintenance with a Natural Dopaminergic Agonist: A Cautionary Note”. Journal of Addiction Research and Therapy 4.2 (2013): 10.4172/2155-6105.1000146.
  35. Hill E., et al. “Long term Suboxone™ emotional reactivity as measured by automatic detection in speech”. PLoS One 8.7 (2013): e69043.
  36. Goh ET., et al. “Review article: pharmacotherapy for alcohol dependence - the why, the what and the wherefore”. Alimentary Pharmacology and Therapeutics 45.7 (2017): 865-882.
  37. Kotyuk E., et al. “Co-occurrences of substance use and other potentially addictive behaviors: Epidemiological results from the Psychological and Genetic Factors of the Addictive Behaviors (PGA) Study”. Journal of Behavioral Addictions 9.2 (2020): 272-288.
  38. Blum K., et al. “rsfMRI effects of KB220Z™ on neural pathways in reward circuitry of abstinent genotyped heroin addicts”. Postgraduate Medical Journal 127.2 (2015): 232-241.
  39. Gold MS., et al. “A Shared Molecular and Genetic Basis for Food and Drug Addiction: Overcoming Hypodopaminergic Trait/State by Incorporating Dopamine Agonistic Therapy in Psychiatry”. Psychiatric Clinics of North America 38.3 (2015): 419-462.
  40. Kalebasi N., et al. “Blunted responses to reward in remitted post-traumatic stress disorder”. Brain Behavior 5.8 (2015): e00357.
  41. Wang L., et al. “Abnormal gray matter volume and resting-state functional connectivity in former heroin-dependent individuals abstinent for multiple years”. Addiction Biology 21.3 (2016): 646-656.
  42. Schmidt LG., et al. “Different allele distribution of a regulatory MAOA gene promoter polymorphism in antisocial and anxious-depressive alcoholics”. Journal of Neural Transmission (Vienna). 107.6 (2000): 681-689.
  43. Borsook D., et al. “Reward deficiency and anti-reward in pain chronification”. Neuroscience and Biobehavioral Reviews 68 (2016): 282-297.
  44. Minozzi S., et al. “Oral naltrexone maintenance treatment for opioid dependence”. Cochrane Database System Review 16.2 (2011): CD001333.
  45. Bowirrat A., et al. “Relationship between dopaminergic neurotransmission, alcoholism, and Reward Deficiency syndrome”. American Journal of Medical Genetics 132B (2005): 29-37.
  46. Robison LS., et al. “Exercise Reduces Dopamine D1R and Increases D2R in Rats: Implications for Addiction”. Medicine and Science in Sports and Exercise 50.8 (2018): 1596-1602.
  47. Blum K., et al. “Pro-Dopamine Regulator - (KB220) to Balance Brain Reward Circuitry in Reward Deficiency Syndrome (RDS)”. Journal of Reward Deficiency Syndrome and Addiction Science 3.1 (2017): 3-13.
  48. Jeynes KD and Gibson EL. “The importance of nutrition in aiding recovery from substance use disorders: A review”. Drug and Alcohol Dependence 179 (2017): 229-239.
  49. Carroll KM and Kiluk BD. “Cognitive behavioral interventions for alcohol and drug use disorders: Through the stage model and back again”. Psychology of Addictive Behaviors 31.8 (2017): 847-861.
  50. Jansen JM., et al. “Resting state connectivity in alcohol dependent patients and the effect of repetitive transcranial magnetic stimulation”. European Neuropsychopharmacology 25.12 (2015): 2230-2239.
  51. Cameron JD., et al. “Brain on Fire: Incentive Salience, Hedonic Hot Spots, Dopamine, Obesity, and Other Hunger Games”. Annual Review of Nutrition 37 (2017): 183-205.
  52. Wang TR., et al. “Deep brain stimulation for the treatment of drug addiction”. Neurosurgery Focus 45.2 (2018): E11.
  53. Schroeder RD and Higgins GE. “You Are What You Eat: The Impact of Nutrition on Alcohol and Drug Use”. Substance Use and Misuse 52.1 (2017): 10-24.
  54. Howe WM and Kenny PJ. “Drug Addiction: Mechanisms of Nicotine Dependence Unmasked by Gene Editing”. Current Biology 28.20 (2018): R1205-R1207.
  55. Blum K., et al. “Promoting Precision Addiction Management (PAM) to Combat the Global Opioid Crisis”. Biomedical Journal of Scientific and Technical Research 2.2 (2018): 1-4.
  56. Bali P., et al. “Methylation, memory and addiction”. Epigenetics 6.6 (2011): 671-674.
  57. Febo M., et al. “Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z”. PLoS One 12.4 (2017): e0174774.
  58. Blum K., et al. “Psychostimulant use disorder emphasizing methamphetamine and the opioid -dopamine connection: Digging out of a hypodopaminergic ditch”. Journal of the Neurological Sciences 420 (2020): 117252.




Citation: Kenneth Blum.,et al.“Should We Embrace the Incorporation of Genetically Guided “Dopamine Homeostasis” in the Treatment of Reward Deficiency Syndrome (RSD) as a Frontline Therapeutic Modality?”. Acta Scientific Neurology 4.2 (2021): 17-24.


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