Genetic addiction risk score GARS trade a predictor of vulnerability to opioid dependence

Abstract

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 epigenetic, may predispose individuals to addictive behaviors and altered pain tolerance. This discussion authored by a group of concerned scientists and clinicians examines the Genetic Addiction Risk Score (GARS), the first test to accurately predict vulnerability to pain, addiction, and other compulsive behaviors, defined as Reward Deficiency Syndrome (RDS). Innovative strategies to combat epidemic opioid, iatrogenic prescription drug abuse and death, based on the role of dopaminergic tone in pain pathways, are 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. Pharmacogenomic testing of candidate genes like CB1, mu receptors, and PENK might result in pharmacogenomic, personalized solutions, and improved clinical outcomes. Genetically identifying risk for all RDS behaviors, especially in compromised populations, may be a frontline tool to assist municipalities to provide better resource allocation.

The Negative Affect of Protracted Opioid Abstinence: Progress and Perspectives From Rodent Models

“…Future work will identify the nature of MOR-expressing neurons that directly respond to repeated opioid stimulation throughout reward-aversion networks, characterize their adapted phenotype in opioid-abstinent animals, and hopefully position these primary events in the broader picture of MOR-associated brain aversion networks (101). In the context of the opioid epidemic, this knowledge will help to develop the much-needed innovative approaches for OUD prevention (102)(103)(104) and treatment (105).…”

The Science of Addiction Through the Lens of Opioid Treatment for Chronic Noncancer Pain

“…They play a role in responses to and metabolism of addictive substances, and, most likely, the experience of rewarding effects. Genetic factors affect risk differently during various stages in the development of addiction (Ballantyne & LaForge, 2007;Blum et al, 2018). Each year, millions of people are exposed to addictive substances by being prescribed them or using them recreationally.…”

“…The first genetic correlation to addiction found relates to severe alcoholism. The first gene discovered, the dopamine D2 receptor gene, is associated with higher rates of alcoholism and established the dopaminergic reward system as central to addictive behaviors (Blum et al, 2018). Hundreds of other genes that underlie addiction have since been established.…”

“…Several genome-wide association study reports indicate that the genetic risk for opioid addiction is conveyed by many alleles, each with a small effect (Berrettini, 2017). Overall, genes act in several ways: via altered metabolism of the drug; altered function of the drug receptor; or altered general mechanisms of addiction, such regulation of stress responses, emotion, and behavioral control (Blum et al, 2018;Ducci & Goldman, 2012). Gene variants of the serotonergic, dopaminergic, GABAergic and other neurotransmission systems are associated with impulsivity, novelty seeking, risk-taking, and other personality traits that may influence early stages of drug use.…”

The Benefits of Genetic Addiction Risk Score (GARS™) Testing in Substance Use Disorder (SUD)

“…Individuals who possess reward gene polymorphisms or variations, will, given environmental insult be at risk for impulsive, compulsive, and addictive behaviors. Reward Deficiency Syndrome (RDS) is a term used to embrace and characterize these genetically induced behaviors [12]. Any and all of these pathological behaviors, as well as psychoactive drug-abuse, are candidates for addiction including tolerance and dependence.…”