Researching Mitigation of Alcohol Binge Drinking in Polydrug Abuse: KCNK13 and RASGRF2 Gene(s) Risk Polymorphisms Coupled with Genetic Addiction Risk Severity (GARS) Guiding Precision Pro-Dopamine Regulation

Abstract

Excessive alcohol intake, e.g., binge drinking, is a serious and mounting public health problem in the United States and throughout the world. Hence the need for novel insights into the underlying neurobiology that may help improve prevention and therapeutic strategies. Therefore, our group employed a darkness-induced alcohol intake protocol to define the reward deficiency domains of alcohol and other substance use disorders in terms of reward pathways’ reduced dopamine signaling and its restoration via specifically-designed therapeutic compounds. It has been determined that KCNK13 and RASGRF2 genes, respectively, code for potassium two pore domain channel subfamily K member 13 and Ras-specific guanine nucleotide-releasing factor 2, and both genes have important dopamine-related functions pertaining to alcohol binge drinking. We present a hypothesis that identification of KCNK13 and RASGRF2 genes’ risk polymorphism, coupled with genetic addiction risk score (GARS)-guided precision pro-dopamine regulation, will mitigate binge alcohol drinking. Accordingly, we review published reports on the benefits of this unique approach and provide data on favorable outcomes for both binge-drinking animals and drunk drivers, including reductions in alcohol intake and prevention of relapse to drinking behavior. Since driving under the influence of alcohol often leads to incarceration rather than rehabilitation, there is converging evidence to support the utilization of GARS with or without KCNK13 and RASGRF2 risk polymorphism in the legal arena, whereby the argument that “determinism” overrides the “free will” account may be a plausible defense strategy. Obviously, this type of research is tantamount to helping resolve a major problem related to polydrug abuse.

The First Exploratory Personalized Medicine Approach to Improve Bariatric Surgery Outcomes Utilizing Psychosocial and Genetic Risk Assessments: Encouraging Clinical Research

“…The development of this genetic assessment was initiated by Blum's laboratory in 2014 published in Molecular Neurobiology [33]. Since that time the same authors have published human trials concerning various applications of GARS in clinical medicine with significantly significant results [11,13,14,16,[65][66][67][68][69][70][71][72][73][74][75][76][77][78]. Moreover, since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including GWAS.…”

Neurogenetics and Epigenetics of Loneliness

“…Consequently, addicted individuals use drugs not to experience "high", but merely to feel normal or "get straight", depending on the extent of impairment. 11,27,68 There are important genetic variations in vulnerability to drug addiction, yet environmental factors such as stress and social defeat also alter brain reward mechanisms to impart epigenetic vulnerability to addiction 11,24,25,27,39,[69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85] in the context of its biopsychosocial nature. 86 Addiction, exemplified by combined reward deficiency and anti-reward syndrome, is marked by a dysfunctional brain reward circuitry.…”

A Pharmacogenomics-Based In Silico Investigation of Opioid Prescribing in Post-operative Spine Pain Management and Personalized Therapy

“…The statistical analyses found the OR, 95% CI for OR, and a post-risk for 8% estimation of the population's alcoholism prevalence showed a significant detection. The OR results indicated significance for COMT, OPRM1, DRD2, DRD3, DRD4, DAT1, and 5HTT at 5% (Blum et al 2018 , 2020 , 2021 ; Blum et al 2022a , b ; Blum et al 2022a , b ; Fried et al 2020 ; Moran et al 2021 ; Bajaj et al 2022 ; Dennen et al 2022 ; Gondré-Lewis et al 2022 ; Gupta et al 2022 ; Vereczkei et al 2022 ; Thanos et al 2023a , b ; Thanos et al 2023a , b ). Consequently, this study aimed to explore the most effective pharmacogenomic approach to managing spinal pain in postoperative patients by analyzing potential actionable genetic variants associated with FDA-approved drugs targeting specific receptors, that is, the genes themselves (Table 2 ).…”