Invited Commentary: In a Genomic Era, Should We Promote Dopamine Homeostasis to Treat Opiate/ Opioid Abuse, Instead of Blocking Brain Dopamine Function?

We are currently in a genomics era with important implications for the field of psychiatry. An understanding of DNA, as well as polymorphic changes affecting the brain’s reward circuitry, has provided a new way of approaching and thinking about addictive behaviors. Our current goal is to provide a foundation for more accurate genetic diagnoses as well, as the application of dopamine agonist therapy (pro-dopamine regulation), in order to balance dopaminergic activation. Based upon our extensive research, we are proposing a novel approach which challenges the Addiction recovery field to utilize these tools by introducing them into inpatient/outpatient addiction treatment programs The following tools, we hope, will change the recovery landscape: The Genetic Addiction Risk Score (GARS™) for Reward Deficiency Syndrome (RDS) diagnoses; the Comprehensive Analysis Of Reported Drugs (CARD™) to establish compliance of prescribed medications and abstinence during treatment; natural Dopamine agonistic therapy (KB220™); mRNA (patent pending) to resolve pre-and post-candidate gene expressions in Reward Deficiency Syndrome (RDS). As a result we have dubbed, this paradigm shift as: “The Reward Deficiency Solutions System (RDSS™).”Wc 180Keywords: Genome, Genetic Addiction Risk Score (GARS), KB220 variants, Pro-Dopamine Regulation, Pain, Opiate/opioid epidemic

[1]  D. Barch,et al.  Preliminary evidence that negative symptom severity relates to multilocus genetic profile for dopamine signaling capacity and D2 receptor binding in healthy controls and in schizophrenia. , 2017, Journal of psychiatric research.

[2]  K. Blum,et al.  Common Neurogenetic Diagnosis and Meso-Limbic Manipulation of Hypodopaminergic Function in Reward Deficiency Syndrome (RDS): Changing the Recovery Landscape , 2016, Current neuropharmacology.

[3]  N. Volkow,et al.  Re-energizing the Development of Pain Therapeutics in Light of the Opioid Epidemic , 2016, Neuron.

[4]  K. Blum,et al.  Fifty Years in the Development of a Glutaminergic-Dopaminergic Optimization Complex (KB220) to Balance Brain Reward Circuitry in Reward Deficiency Syndrome: A Pictorial. , 2016, Austin addiction sciences.

[5]  C. Allis,et al.  Histone arginine methylation in cocaine action in the nucleus accumbens , 2016, Proceedings of the National Academy of Sciences.

[6]  D. Wack,et al.  Attenuated Tonic and Enhanced Phasic Release of Dopamine in Attention Deficit Hyperactivity Disorder , 2015, PloS one.

[7]  K. Blum,et al.  Neurogenetics and gene therapy for reward deficiency syndrome: are we going to the Promised Land? , 2015, Expert opinion on biological therapy.

[8]  K. Blum,et al.  Molecular Genetic Testing in Reward Deficiency Syndrome (RDS): Facts and Fiction , 2015, Journal of reward deficiency syndrome.

[9]  K. Blum,et al.  Reward Deficiency Syndrome: Attentional/Arousal Subtypes, Limitations of Current Diagnostic Nosology, and Future Research , 2015, Journal of reward deficiency syndrome.

[10]  S. Hernández-Díaz,et al.  Patterns of Opioid Utilization in Pregnancy in a Large Cohort of Commercial Insurance Beneficiaries in the United States , 2014, Anesthesiology.

[11]  K. Blum,et al.  Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children? , 2014, Postgraduate medicine.

[12]  E. Kalso,et al.  Expect analgesic failure; pursue analgesic success , 2013, BMJ.

[13]  O. Gokcumen,et al.  Balancing Selection on a Regulatory Region Exhibiting Ancient Variation That Predates Human–Neandertal Divergence , 2013, PLoS genetics.

[14]  D. Goodin The Genetic Basis of Complex Human Disease: Extending the Utility of Twin Studies (P05.123) , 2012 .

[15]  M. Bedford,et al.  Histone arginine methylation , 2011, FEBS letters.

[16]  K. Blum,et al.  Neuro-chemical activation of brain reward meso-limbic circuitry is associated with relapse prevention and drug hunger: a hypothesis. , 2011, Medical hypotheses.

[17]  R. Bhardwaj,et al.  Prevalence and correlates of epileptic seizure in substance‐abusing subjects , 2009, Psychiatry and clinical neurosciences.

[18]  Thomas J. H. Chen,et al.  LG839: Anti-obesity effects and polymorphic gene correlates of reward deficiency syndrome , 2008, Advances in therapy.

[19]  C. A. Gordon,et al.  Reward deficiency syndrome in obesity: A preliminary cross-sectional trial with a genotrim variant , 2006, Advances in therapy.

[20]  Yongli Xi,et al.  Increasing deaths from opioid analgesics in the United States , 2006, Pharmacoepidemiology and drug safety.

[21]  Thomas J. H. Chen,et al.  The Reward Deficiency Syndrome: A Biogenetic Model for the Diagnosis and Treatment of Impulsive, Addictive and Compulsive Behaviors , 2000, Journal of psychoactive drugs.

[22]  J O Rinne,et al.  The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers , 1998, Molecular Psychiatry.

[23]  M. Owen,et al.  The genetic basis of complex human behaviors. , 1994, Science.

[24]  E P Noble,et al.  Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. , 1991, Archives of general psychiatry.

[25]  K. Blum,et al.  Allelic association of human dopamine D2 receptor gene in alcoholism. , 1990, JAMA.

[26]  Olga Boric-Lubecke,et al.  Vital signs. , 2017, Nursing standard (Royal College of Nursing (Great Britain) : 1987).

[27]  K. Blum,et al.  THE BENEFITS OF CUSTOMIZED DNA DIRECTED NUTRITION TO BALANCE THE BRAIN REWARD CIRCUITRY AND REDUCE ADDICTIVE BEHAVIORS. , 2016, Precision medicine.

[28]  Carlos Cepeda,et al.  Functional Differences Between Direct and Indirect Striatal Output Pathways in Huntington's Disease. , 2012, Journal of Huntington's disease.

[29]  K. Blum,et al.  "Liking" and "wanting" linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry. , 2012, Current pharmaceutical design.

[30]  C. A. Gordon,et al.  Genotrim, a DNA-customized nutrigenomic product, targets genetic factors of obesity: hypothesizing a dopamine-glucose correlation demonstrating reward deficiency syndrome (RDS). , 2007, Medical hypotheses.

[31]  K. Blum,et al.  The D2 dopamine receptor gene as a predictor of compulsive disease: Bayes' theorem. , 1995, Functional neurology.

[32]  D. Borsook,et al.  Neuroscience and Biobehavioral Reviews Reward Deficiency and Anti-reward in Pain Chronification , 2022 .