A review of DNA risk alleles to determine epigenetic repair of mRNA expression to prove therapeutic effectiveness in reward deficiency syndrome (RDS): Embracing Precision Behavioral Management

This is a review of research on Precision Behavioral Management of substance use disorder (SUD). America is experiencing a high prevalence of substance use disorder, primarily involving legal and illegal opioid use. A 3000% increase in treatment for substance abuse has occurred between 2000 and 2016. Unfortunately, present day treatment of opioid abuse involves providing replacement therapy with powerful opioids to, at best, induce harm reduction, not prophylaxis. These interventions do not enhance gene expression and restore the balance of the brain reward system\u27s neurotransmitters. We are proposing a generalized approach called Precision Behavioral Management . This approach includes 1) using the Genetic Addiction Risk Severity (GARS, a 10 candidate polymorphic gene panel shown to predict ASI-alcohol and drug severity) to assess early pre-disposition to substance use disorder; 2) using a validated reward deficiency syndrome (RDS) questionnaire; 3) utilization of the Comprehensive Analysis of Reported Drugs (CARD™) to assess treatment compliance and abstinence from illicit drugs during treatment, and, importantly; 4) utilization of a Pro-dopamine regulator (KB220) (via IV or oral [KB220Z] delivery systems) to optimize gene expression, restore the balance of the Brain Reward Cascade\u27s neurotransmitter systems and prevent relapse by induction of dopamine homeostasis, and; 5) utilization of targeted DNA polymorphic reward genes to direct mRNA genetic expression profiling during the treatment process. Incorporation of these events can be applied to not only the under-considered African-American RDS community, but all victims of RDS, as a demonstration of a paradigm shift that uniquely provides a novel putative standard of care based on DNA guided precision nutrition therapy to induce dopamine homeostasis and rebalance neurotransmitters in the Brain Reward Cascade. We are also developing a Reward Deficiency Syndrome Diagnostic Criteria (RDSDC) to assist in potential tertiary treatment

Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD

Background: Addictive-like behaviors (e.g., hoarding and shopping) may be the result of the cumulative effects of dopaminergic and other neurotransmitter genetic variants as well as elevated stress levels. We, therefore, propose that dopamine homeostasis may be the preferred goal in combating such challenging and unwanted behaviors, when simple dopaminergic activation through potent agonists may not provide any resolution. Case presentation: C.J. is a 38-year-old, single, female, living with her mother. She has a history of substance use disorder as well as attention deficit hyperactivity disorder, inattentive type. She had been stable on buprenorphine/naloxone combination and amphetamine, dextroamphetamine mixed salts for many years when unexpectedly she lost her job for oversleeping and not calling into work. KB200z (a pro-dopamine compound) was added to her regimen for complaints of low drive and motivation. After taking this nutraceutical for 4 weeks, she noticed a marked improvement in her mental status and many behaviors. She noted that her shopping and hoarding addictions had appreciably decreased. Furthermore, her lifelong history of terrifying lucid dreams was eliminated. Finally, she felt more in control; her locus of control shifted from external to more internal. Discussion: The hypothesis is that C.J.’s reported, behavioral, and psychological benefits resulted from the pro-dopamine-regulating effect of KB220Z across the brain reward system. Conclusions: This effect, we surmise, could be the result of a new dopamine balance, across C.J.’s brain reward system. Dopamine homeostasis is an effect of KB220Z seen in both animal and human placebo-controlled fMRI experiments

A systematic, intensive statistical investigation of data from the Comprehensive Analysis of Reported Drugs (CARD) for compliance and illicit opioid abstinence in substance addiction treatment with buprenorphine/naloxone

BACKGROUND: Buprenorphine and naloxone (bup/nal), a combination partial mu receptor agonist and low-dose delta mu antagonist, is presently recommended and used to treat opioid-use disorder. However, a literature review revealed a paucity of research involving data from urine drug tests that looked at compliance and abstinence in one sample. METHOD: Statistical analysis of data from the Comprehensive Analysis of Reported Drugs (CARD) was used to assess compliance and abstinence during treatment in a large cohort of bup/nal patients attending chemical-dependency programs from eastern USA in 2010 and 2011. RESULTS: Part 1: Bup/nal was present in 93.4% of first (n = 1,282; p \u3c.0001) and 92.4% of last (n = 1,268; p \u3c.0001) urine samples. Concomitantly, unreported illicit drugs were present in 47.7% (n = 655, p =.0261) of samples. Patients who were compliant to the bup/nal prescription were more likely than noncompliant patients to be abstinent during treatment (p =.0012; odds ratio = 1.69 with 95% confidence interval (1.210, 2.354). Part 2: An analysis of all samples collected in 2011 revealed a significant improvement in both compliance (p \u3c 2.2 × 1

Downskilling: Changes in Employer Skill Requirements Over the Business Cycle

Using a novel database of 82.5 million online job postings, we show that employer skill requirements fell as the labor market improved from 2010 to 2014. We find that a 1 percentage point reduction in the local unemployment rate is associated with a roughly 0.27 percentage point reduction in the fraction of jobs requiring at least a bachelor's degree and a roughly 0.23 percentage point reduction in the fraction requiring five or more years of experience. This pattern is established using multiple measures of labor availability, is bolstered by similar trends along heretofore unmeasured dimensions of skill, and even occurs within firm-job title pairs. We further confirm the causal effect of labor market tightening on skill requirements using a natural experiment based on the fracking boom in the United States as an exogenous shock to the local labor supply in tradable, non-fracking industries. These industries are not plausibly affected by local demand shocks or natural gas extraction technology, but still show fewer skill requirements in response to tighter labor markets. Our results imply this labor market-induced downskilling reversed much of the cyclical increase in education and experience requirements that occurred during the Great Recession

Hypothesizing in the Face of the Opioid Crisis Coupling Genetic Addiction Risk Severity (GARS) Testing with Electrotherapeutic Nonopioid Modalities Such as H-Wave Could Attenuate Both Pain and Hedonic Addictive Behaviors

In the United States, amid the opioid overdose epidemic, nonaddicting/nonpharmacological proven strategies are available to treat pain and manage chronic pain effectively without opioids. Evidence supporting the long-term use of opioids for pain is lacking, as is the will to alter the drug-embracing culture in American chronic pain management. Some pain clinicians seem to prefer classical analgesic agents that promote unwanted tolerance to analgesics and subsequent biological induction of the “addictive brain”. Reward genes play a vital part in modulation of nociception and adaptations in the dopaminergic circuitry. They may affect various sensory and affective components of the chronic pain syndromes. The Genetic Addiction Risk Severity (GARS) test coupled with the H-Wave at entry in pain clinics could attenuate pain and help prevent addiction. The GARS test results identify high-risk for both drug and alcohol, and H-Wave can be initiated to treat pain instead of opioids. The utilization of H-Wave to aid in pain reduction and mitigation of hedonic addictive behaviors is recommended, notwithstanding required randomized control studies. This frontline approach would reduce the possibility of long-term neurobiological deficits and fatalities associated with potent opioid analgesics

A novel precision approach to overcome the “addiction pandemic” by incorporating genetic addiction risk severity (Gars) and dopamine homeostasis restoration

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

Upskilling: Do Employers Demand Greater Skill When Skilled Workers Are Plentiful?

Using a large database of online job postings, we demonstrate that employee skill requirements rise when there is a larger supply of relevant job seekers. We identify this effect using variation across time, occupations, and places, which allows us to control for potentially confounding factors. We further exploit the natural experiment arising from troop withdrawals from Iraq and Afghanistan over this period as a shock to local, occupation-specific labor supply. Our estimates imply that the increase in national unemployment rates from 2007 to 2010 increased requirements for a bachelor's degree within occupations by 2.2 percentage points and increased the fraction requiring two or more years of experience by 3.5 percentage points

Hypodopaminergia and “precision behavioral management” (PBM): It is a generational family affair

Background/Aims: This case series presents the novel Genetic Addiction Risk Score (GARS®) coupled with a customized pro-dopamine regulator matched to polymorphic reward genes having a hypodopaminergic risk. Methods: The proband is a female with a history of drug abuse and alcoholism. She experienced a car accident under the influence and voluntarily entered treatment. Following an assessment, she was gen-otyped using the GARS, and started a neuronutrient with a KB220 base indicated by the identified pol-ymorphisms. She began taking it in April 2018 and continues. Results: She had success in recovery from Substance Use Disorder (SUD) and improvement in so-cialization, family, economic status, well-being, and attenuation of Major Depression. She tested negative over the first two months in treatment and a recent screening. After approximately two months, her parents also decided to take the GARS and started taking the recommended variants. The proband’s father (a binge drinker) and mother (no SUD) both showed improvement in various behavioral issues. Finally, the proband’s biological children were also GARS tested, showing a high risk for SUD. Conclusion: This three-generation case series represents an example of the impact of genetic infor-mation coupled with an appropriate DNA guided “Pro-Dopamine Regulator” in recovery and enhancement of life

High Genetic Addiction Risk Score (GARS) in Chronically Prescribed Severe Chronic Opioid Probands Attending Multi-pain Clinics: an Open Clinical Pilot Trial

Millions of Americans experience pain daily. In 2017, opioid overdose claimed 64,000 lives increasing to 84,000 lives in 2020, resulting in a decrease in national life expectancy. Chronic opioid use results in dependency, drug tolerance, neuroadaptation, hyperalgesia, potential addictive behaviors, or Reward Deficiency Syndrome (RDS) caused by a hypodopaminergia. Evaluation of pain clinic patients with the Genetic Addiction Risk Score (GARS) test and the Addiction Severity Index (ASI- Media Version V) revealed that GARS scores equal to or greater than 4 and 7 alleles significantly predicted drug and alcohol severity, respectively. We utilized RT-PCR for SNP genotyping and multiplex PCR/capillary electrophoresis for fragment analysis of the role of eleven alleles in a ten-reward gene panel, reflecting the activity of brain reward circuitry in 121 chronic opioid users. The study consisted of 55 males and 66 females averaging ages 54 and 53 years of age, respectively. The patients included Caucasians, African Americans, Hispanics, and Asians. Inclusion criteria mandated that the Morphine Milligram Equivalent (MME) was 30–600 mg/day (males) and 20 to 180 mg/day (females) for treatment of chronic pain over 12 months. Ninety-six percent carried four or more risk alleles, and 73% carried seven or more risk alleles, suggesting a high predictive risk for opioid and alcohol dependence, respectively. These data indicate that chronic, legally prescribed opioid users attending a pain clinic possess high genetic risk for drug and alcohol addiction. Early identification of genetic risk, using the GARS test upon entry to treatment, may prevent iatrogenic induced opioid dependence