GENETIC ADDICTION RISK SCORE (GARS®) SCREENING: COMBATIVE EARLY IDENTIFICATION AND INTERVENTION IN FACE OF AMERICAS DRUG EPIDEMIC

Kenneth Blum, PhD, DHL, David Baron, DO, and David Siwicki, MD

INTRODUCTION
The current opioid addiction epidemic has become a leading public health crisis worldwide. In addition to the significant morbidity and mortality associated with over use, the financial costs in the US alone exceed $78 billion dollars. The impact of this global crisis was highlighted by the designation of International Overdose Awareness Day, on August 31, 2018. Extant Addiction research has demonstrated the key to effective treatment is early identification and treatment of drug use and subsequent early intervention. Like cancer, heart disease and other chronic illnesses, the longer they go untreated, the more challenging they are to effectively treat. The ability to identify an at-risk population, particularly in childhood would be a major step forward in the attempt to alter the negative impact on individual and population health. Blum’s description of the Reward deficiency Syndrome (RDS) has gained wide acceptance in the scientific community as a critical factor in the etiology of addictive behaviors of all types. The lack of dopamine homeostasis may play a critical role in the development of addictive behaviors, and paradoxically, as well as offering effective treatment options. This article presents a new strategy to help identify at-risk children for the future development of addictions through the use of the validated Genetic Addiction Risk Score (GARS). The ability to identify at-risk children, and follow them prospectively throughout their teenage years, monitoring their drug use/abuse, could have significant public health implications, while expanding our understanding of the core biology of addiction. An epidemic of this size and magnitude will require bold, innovative interventions/screenings, educational awareness campaigns, based on high-quality scientific data. The authors offer a potential strategy to achieve this important goal.

The Epidemic
The United States is in the midst of an opioid overdose epidemic. Between 1999 and 2010, prescription opioid–related overdose deaths increased significantly in parallel with increased prescribing of opioids. In 2017, opioid-involved drug overdoses accounted for 72,000 deaths. Additionally, an estimated 2 million individuals in the United States have opioid use disorder (addiction) associated with prescription opioids, accounting for an estimated $78.5 billion in economic costs annually. In the United Sates alone, every seventeen minutes another person overdoses. Goals include increasing awareness about the risk for overdose possibly through genetic testing, reducing stigma associated with drug overdose deaths, providing information about community services, expanding recovery high schools, and preventing and reducing drug-related harm by supporting evidence-based policy and practice and early intervention. (https://www.overdoseday.com).

Opioid deaths, particularly those involving illicit opioids, continue to increase. As described in a report of Morbid Mortality Weekly Report (MMWR), illicit opioids were detected in approximately three of four opioid overdose deaths compared with nearly four of 10 for prescription opioids, in the 11 states examined. Enhanced surveillance for opioid overdose deaths facilitates the classification of deaths involving prescription and illicit opioids as well as identifying missed opportunities for prevention/early intervention and response (https://www.cdc.gov/drugoverdose/index.html).

It is now established that the overall cost of the opioid crisis is north of one trillion dollars. While there are a number of proven strategies available to manage chronic pain effectively without opioids, as well as aberrant drug seeking, it is agreed by all the major agencies that as a unified community, we are being challenged to provide alternative non-addicting and non-pharmacological alternatives to assist in pain and addiction attenuation.

We the authors of this treatise are convinced that the older paradigm only keeping people maintained on for example opioids (buprenorphine/naloxone and naltrexone combinations) needs to change if we are to truly change the drug-embracing culture in chronic pain and addiction management. The missing link is to achieve dopamine homeostasis early on through risk identification with GARS.

In America, pain is a significant public health problem that costs society at least $560-$635 billion annually, an amount equal to about $2,000.00 for everyone living in the USA. This includes the total incremental cost of health care due to pain ranging between $261 to $300 billion and $297-$336 billion due to lost productivity (based on days of work missed, hours of work lost and lower wages).

In 2017, a total of almost 4 million babies were born in the United States of America. We are raising the question regarding the wisdom and competence of the existing treatment paradigm based on the estimate that total societal costs of the current opioid epidemic in the USA alone are north of one-trillion dollars. It seems logical, appropriate, and prudent that screening for the risk of addiction at birth would significantly reduce the overall cost to society. If we then add on the number of lives that could be saved by early detection, but died, which has been determined to be approximately 72,000 in 2017, at a 50 percent level, we could potentially save 35,000 lives. Coupling the actual cost to society and the reduction of pain and grief to families and friends across the American Nation, which cannot be objectively measured, the value proposition of a genetic addiction risk score (GARS) screening at birth although premature, should not be dismissed.

As a community of specialists in the United States, we are compelled to find alternative solutions to help reward deficiency victims overcome unhealthy and even dangerous excessive reward-seeking behaviors without promoting unwanted tolerance to analgesics that can induce the “addictive brain” by compromising the hard wiring in the medial forebrain bundle (MFB).

It is noteworthy that the brain reward center plays a key role in the modulation of many mood disorders, and at birth genetic polymorphisms may impact one’s ability to achieve pleasure from natural every day experiences. In at least 100 million people living in America, and many more worldwide, carrying the DRD2 A1 allele at birth may predispose them to a blunted reward processing event expressing the unwanted concept of “thrill is gone”, or in essence, never occurred. Unfortunately, these victims of RDS, as the child becomes adolescent, in order to obtain a “dopamine fix”, engage in excessive unhealthy and even dangerous reward-inducing thoughts and seek out anything else that will enhance dopaminergic signaling such as drugs, sex, gaming, food, etc. This well-known phenomenon is indeed the real gateway and root cause of aberrant drug and nondrug seeking behavior. Early identification of this risk, due to genetic antecedents that lead to impaired resting state functional connectivity and reduced dopamine tone, should be seriously considered as we face the global epidemic prematurely killing our young generation independent of class. Some states in the USA are now seriously addressing this dilemma.

Analytics of Genetic Addiction Risk Score (GARS)

To understand our goal involving the development of the USA patented Genetic Addiction Risk Score (GARS®) panel of reward gene polymorphisms and a clinical outcome, the rationale is provided herein. The interaction of neurotransmitters and genes that control the release of dopamine is the Brain Reward Cascade (BRC). Variations within the BRC, whether genetic or environment (epigenetic), may predispose individuals to addictive behaviors and altered pain tolerance. This concept has been established
by a group of concerned scientists and clinicians that examined the GARS, the first test to accurately predict vulnerability to pain, addiction, and other compulsive behaviors, defined as RDS with particular emphasis for OUD and SUD.

Innovative strategies to combat the epidemic of opioid, iatrogenic prescription drug abuse and death, based on the role of dopaminergic tone in pain pathways, have been proposed. Sensitivity to pain may reside in the mesolimbic projection system, where genetic polymorphisms associate with a predisposition to pain vulnerability or tolerance. They provide unique therapeutic targets that could assist in the treatment of pain and identify risk for subsequent addiction involving RDS and anti-reward symptomatology.

GARS

Geneus Genomic Testing Center (GGTC), in conjunction with Dominion Diagnostics and Colorado University, in unpublished but submitted research (a 4-year sojourn) sought to address genetic risk for alcohol/drug seeking by evaluating the combined effect of reward gene polymorphisms [a genetic addiction risk score (GARS) of 11polymorphisms and ten genes] contributing to a hypodopaminergic-trait. It is important to realize that the GARS test as a predictor of high risk for RDS behaviors that have been associated with the Addiction Severity Index ( ASI) , which is a clinical predictive not diagnostic test, cannot display false positives because the GARS test measures an entire panel of gene polymorphisms to predict drug and alcohol severity as a cluster.

Test results show that if a patient carries any combination of
4 GARS risk alleles, it is predictive of drug severity, or any combination of 7 GARS risk alleles, the test is predictive of alcohol severity. It is of interest that it has been found that 100% of these patients from chemical dependency treatment programs carry at least one risk allele.

We are asking the scientific community to consider the benefits vs. the risk of identifying genetic predisposition of RDS through GARS testing early. Of significance, blood is not needed. Does this actually constitute “Emperor’s New Clothes”? Admittedly, this approach is outside the box of conventional dogma. It represents a technological advancement providing a very advantageous paradigm shift in the assessment of risk for addictive, obsessive, compulsive and impulsive behaviors. However, a number of clinics are adopting this new paradigm shift. The GARS test is ahead of its time and would certainly benefit by additional population genetic studies as well as public education to reduce the fear related to labelling someone at an early age with a predisposition or risk for RDS and subsequent addictive seeking behavior. Moreover, the GARS test would provide an important strategy to increase the awareness of potential benefits associated with early identification and subsequent early intervention. (see Figure 1).

Figure 1. This represents a Tree Analysis whereby we define the problem, parts of the problem, solution and results. In terms of solution it is proposed that amongst other potentials the coupling of

GARS and Precision Neuronutrient termed “Precision Behavioral Management” as well as other prevention strategies including education and awareness (e.g. Recovery High Schools, etc.) along with a pro-dopamine lifestyle (e.g. exercise, dopamine boosting foods, yoga, medication, mindfulness etc.) are all positive. It is our proposal that adoption of these strategies could translate to an attenuation of RDS behaviors.

Challenges of genetic testing include the impact that such knowledge can have on the individual, on one’s sense of self; misunderstanding of the consequences of genetic predisposition and discrimination; and using genetic information to deny persons access to, for example, employment and insurance. Most states have some legislation aimed at preventing discrimination, however, coverage by most state law is spotty. Now with the US Genetic Information Non-Discrimination Act (GINA) [Pub.L110-233,122 Sta.881, enacted May21, 2008 individuals are protected by federal law.

Summary
Possibly knowing a patient’s genetic addiction risk score (GARS), a confidential revelation, could help provide an in- depth mirror of a patient’s brain and assist in prophylaxis, especially in early genetic identification of high risk for addiction. The concept herein is to provide information, not to label, but to warn people, that they should avoid certain risky behaviors that could lead to drug and non-drug aberrant seeking behaviors. In many previous articles from our group, we provided analytic genetic and neurochemical evidence that could help addiction management and pain specialists in providing better care that would eliminate guessing, especially as it relates to becoming an addict. This approach would also present an immensely valuable paradigm shift embracing ‘Precision Addiction Management” and the induction of “Dopamine Homeostasis.”

We are cognizant that genetic information is just one piece to prevention, and as such, it must be coupled with a national awareness campaign and mass education of the pitfalls of reward seeking behavior early on, especially at the high school level. But, taking action is the preeminent priority as the need for urgent action is so great.

One take home message is that while Opioid Substitution Therapy (OST) is important as a way of reducing harm in society, there must be a continual search for better more etiologically rooted solutions, whereby early genetic testing coupled with pro-dopamine regulation seems prudent in face of Americas unwanted drug epidemic.

One question that has been raised involves the suggestion
that genetic screening for addiction risk should occur at birth, following significant on-going research to support this future–forward concept, and not just pretentiously relying on made-up guessing algorithms, analogous with the deceptive façade of the Emperor’s New Clothes.

Kenneth Blum, B.Sc. (Pharmacy), M.Sc., Ph.D. & DHL; received his Ph.D. in Neuropharmacology from New York Medical College and graduated from Columbia University and New Jersey College of Medicine. He also received a doctor of humane letters from Saint Martin’s University Lacey, WA. Dr. Blum has authored over 600 medical articles, chapters, abstracts, journals, and sixteen professional books on a wide variety of psychiatric research subjects, including psychiatric comorbidity, detox, and addiction treatment and psychiatric genetics.

Dr. Siwicki is board certified in emergency medicine and is also certified in addiction medicine. Dr. Siwicki was the co-founder of Dominion Diagnostics LLC; North Kingston, RI which is now the largest privately held toxicology laboratory in the U.S. Dr. Siwicki is also the co – founder of Geneus Health, LLC. He serves as President of Geneus Health and Igene LLC and is a member of Board of Directors on Dominion Diagnostics.
www.GeneusHealth.com

Dr. Baron is a world recognized Psychiatrist specializing in Reward Deficiency behaviors including Sports Psychiatry, ADHD and Substance Use Disorder. He has been educated in a number of institutions of higher learning including Emory University, Temple University, Philadelphia College of Osteopathic Medicine, and residency programs at the University of Southern California. Currently he has accepted the position of Provost of Western University Health Sciences Pomona, California. Dr. Baron has been involved with Global Psychiatry for over 30 years. He is very active in international psychiatric education and collaborative research with global partners. He has also served as Associate dean of International relations at Temple University School of Medicine, Medical Director of Global Health and Assistant Dean of International Affairs for the Keck School of Medicine of USC. He served as Deputy Clinical Director of the National Institutes of Health (NIMH) and Chair of Psychiatry at Temple. His research has been displayed and published in numerous high tiered journals. Dr. Baron has received numerous awards and honors over the years including: Harry Stack Sullivan Award, Concussion in Sports research 2015, Charles Heath Award, Tulane University, Concussion in Youth Sports and 2017-18 Fulbright Distinguished Chair in Brain Science, Youth Concussion.