Alcohol and other substance use disorders share comorbidity with other RDS disorders, i.e., a reduction in dopamine signaling within the reward pathway. RDS is a term that connects addictive, obsessive, compulsive, and impulsive behavioral disorders. An estimated 2 million individuals in the United States have opioid use disorder related to prescription opioids. It is estimated that the overall cost of the illegal and legally prescribed opioid crisis exceeds one trillion dollars. Opioid Replacement Therapy is the most common treatment for addictions and other RDS disorders. Even after repeated relapses, patients are repeatedly prescribed the same opioid replacement treatments. A recent JAMA report indicates that non-opioid treatments fare better than chronic opioid treatments. Research demonstrates that over 50 percent of all suicides are related to alcohol or other drug use. In addition to effective fellowship programs and spirituality acceptance, nutrigenomic therapies (e.g., KB220Z) optimize gene expression, rebalance neurotransmitters, and restore neurotransmitter functional connectivity. KB220Z was shown to increase functional connectivity across specific brain regions involved in dopaminergic function. KB220/Z significantly reduces RDS behavioral disorders and relapse in human DUI offenders. Taking a Genetic Addiction Risk Severity (GARS) test combined with a the KB220Z semi-customized nutrigenomic supplement effectively restores dopamine homeostasis (WC 199).
This article describes a unique therapeutic precision intervention, a formulation of enkephalinase inhibitors, enkephalin, and dopamine-releasing neuronutrients, to induce dopamine homeostasis for detoxification and treatment of individuals genetically predisposed to developing reward deficiency syndrome (RDS). The formulations are based on the results of the addiction risk severity (GARS) test. Based on both neurogenetic and epigenetic evidence, the test evaluates the presence of reward genes and risk alleles. Existing evidence demonstrates that the novel genetic risk testing system can successfully stratify the potential for developing opioid use disorder (OUD) related risks or before initiating opioid analgesic therapy and RDS risk for people in recovery. In the case of opioid use disorders, long-term maintenance agonist treatments like methadone and buprenorphine may create RDS, or RDS may have been in existence, but not recognized. The test will also assess the potential for benefit from medication-assisted treatment with dopamine augmentation. RDS methodology holds a strong promise for reducing the burden of addictive disorders for individuals, their families, and society as a whole by guiding the restoration of dopamine homeostasisthrough anti-reward allostatic neuroadaptations. WC 175
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. To develop an accurate test to help identify those at risk for at least Alcohol Use Disorder (AUD), Blum’s group developed the Genetic Addiction Risk Severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions published from 1990 until 2021. This analysis calculated the Hardy–Weinberg Equilibrium of each polymorphism in cases and controls. If available, the Pearson’s χ2 test or Fisher’s exact test was applied to comparisons of the gender, genotype, and allele distribution. The statistical analyses found the OR, 95% CI for OR, and a post-risk for 8% estimation of the population’s alcoholism prevalence revealed a significant detection. The OR results showed significance for DRD2, DRD3, DRD4, DAT1, COMT, OPRM1, and 5HTT at 5%. While most of the research related to GARS is derived from our laboratory, we are encouraging more independent research to confirm our findings.
Over years, the regular use of cannabis has substantially increased among young adults, as indicated by the rise in cannabis use disorder (CUD), with an estimated prevalence of 8. 3% in the United States. Research shows that exposure to cannabis is associated with hypodopaminergic anhedonia (depression), cognitive decline, poor memory, inattention, impaired learning performance, reduced dopamine brain response-associated emotionality, and increased addiction severity in young adults. The addiction medicine community is increasing concern because of the high content of delta-9-tetrahydrocannabinol (THC) currently found in oral and vaping cannabis products, the cognitive effects of cannabis may become more pronounced in young adults who use these cannabis products. Preliminary research suggests that it is possible to induce 'dopamine homeostasis,' that is, restore dopamine function with dopamine upregulation with the proposed compound and normalize behavior in chronic cannabis users with cannabis-induced hypodopaminergic anhedonia (depression) and cognitive decline. This psychological, neurobiological, anatomical, genetic, and epigenetic research also could provide evidence to use for the development of an appropriate policy regarding the decriminalization of cannabis for recreational use.
While opioids are a powerful class of drugs that inhibit transmission of pain signals, their use is tarnished by the current epidemic of opioid use disorder (OUD) and overdose deaths. Notwithstanding published reports, there remain gaps in our knowledge of opioid receptor mechanisms and their role in opioid seeking behavior. Thus, novel insights into molecular, neurogenetic and neuropharmacological bases of OUD are needed. We propose that an addictive endophenotype may not be entirely specific to the drug of choice but rather may be generalizable to altered brain reward circuits impacting net mesocorticolimbic dopamine release. We suggest that genetic or epigenetic alterations across dopaminergic reward systems lead to uncontrollable self-administration of opioids and other drugs. For instance, diminished availability via knockout of dopamine D3 receptor (DRD3) increases vulnerability to opioids. Building upon this concept via the use of a sophisticated polymorphic risk analysis in a human cohort of chronic opioid users, we found evidence for a higher frequency of polymorphic DRD3 risk allele (rs6280) than opioid receptor µ1 (rs1799971). In conclusion, while opioidergic mechanisms are involved in OUD, dopamine-related receptors may have primary influence on opioid-seeking behavior in African Americans. These findings suggest OUD-targeted novel and improved neuropharmacological therapies may require focus on DRD3-mediated regulation of dopaminergic homeostasis.
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