Coupling Neurogenetics (GARS™) and a Nutrigenomic Based Dopaminergic Agonist to Treat Reward Deficiency Syndrome (RDS): Targeting Polymorphic Reward Genes for Carbohydrate Addiction Algorithms

Abstract

Earlier work from our laboratory, showing anti-addiction activity of a nutraceutical consisting of amino-acid precursors and enkephalinase inhibition properties and our discovery of the first polymorphic gene (Dopamine D2 Receptor Gene [DRD2]) to associate with severe alcoholism serves as a blue-print for the development of “Personalized Medicine” in addiction. Prior to the later genetic finding, we developed the concept of Brain Reward Cascade, which continues to act as an important component for stratification of addiction risk through neurogenetics. In 1996 our laboratory also coined the term “Reward Deficiency Syndrome (RDS)” to define a common genetic rubric for both substance and non-substance related addictive behaviors. Following many reiterations we utilized polymorphic targets of a number of reward genes (serotonergic, Opioidergic, GABAergic and Dopaminergic) to customize KB220 [Neuroadaptogen- amino-acid therapy (NAAT)] by specific algorithms. Identifying 1,000 obese subjects in the Netherlands a subsequent small subset was administered various KB220Z formulae customized according to respective DNA polymorphisms individualized that translated to significant decreases in both Body Mass Index (BMI) and weight in pounds. Following these experiments, we have been successfully developing a panel of genes known as “Genetic Addiction Risk Score” (GARSpDX)™. Selection of 10 genes with appropriate variants, a statistically significant association between the ASI-Media Version-alcohol and drug severity scores and GARSpDx was found A variant of KB220Z in abstinent heroin addicts increased resting state functional connectivity in a putative network including: dorsal anterior cingulate, medial frontal gyrus, nucleus accumbens, posterior cingulate, occipital cortical areas, and cerebellum. In addition, we show that KB220Z significantly activates, above placebo, seed regions of interest including the left nucleus accumbens, cingulate gyrus, anterior thalamic nuclei, hippocampus, pre-limbic and infra-limbic loci. KB220Z demonstrates significant functional connectivity, increased brain volume recruitment and enhanced dopaminergic functionality across the brain reward circuitry. We propose a Reward Deficiency System Solution that promotes early identification and stratification of risk alleles by utilizing GARSDx, allowing for customized nutrigenomic targeting of these risk alleles by altering KB220Z ingredients as an algorithmic function of carrying these polymorphic DNA–SNPS, potentially yielding the first ever nutrigenomic solution for addiction and pain.

Cannabis-Induced Hypodopaminergic Anhedonia and Cognitive Decline in Humans: Embracing Putative Induction of Dopamine Homeostasis

“…However, in chronic cannabis-using adolescents, the goal would be to enhance brain reward functional connectivity [measures the degree of synchrony of the BOLD time-series between different brain regions] and connectivity volume [Voxel-based morphology (VBM)], attenuate depression-like symptoms (anhedonia), and target stress-like anti-reward drug dependence symptoms. Using fMRI of both naïve animals ( 60 ) and heroin abstinent subjects ( 61 ), we confirmed blood-oxygen-level-dependent (BOLD) activation of dopaminergic reward pathways and recruitment of dopamine neuronal firing with KB220Z. These types of fMRI results provide some evidence for dopaminergic activation.…”

Hypothesizing Nutrigenomic-Based Precision Anti-Obesity Treatment and Prophylaxis: Should We Be Targeting Sarcopenia Induced Brain Dysfunction?

“…Out of the genes tested, only the Drd2 gene polymorphism (A1 allele) displayed a significant Pearson Correlation with the number of days on treatment (r = 0.42, P = 0.045). Our group obtained similar outcomes suggesting that DNA-directed targeting of specific modulator genes, in tandem with individualized nutraceutical therapy, offers a unique framework from which to target obesity reduction strategically [ 11 , 12 , 13 , 14 ].…”

Dopamina e comportamento alimentar: polimorfismos em receptores dopaminérgicos e fenótipos relacionados à obesidade

“…Nesse sentido, verificou-se que indivíduos com excesso de peso têm um aumento do wanting e da ingestão energética na ausência de fome e, também, uma diminuição do liking após as refeições. Isso sugere que indivíduos obesos possuem uma dificuldade na obtenção de recompensa, o que os leva a uma procura excessiva pela recompensa alimentar 17,18 .…”