A Systematic Medical Approach to Reward Transformation SMART for Brain Health in Opioid Use Disorder

Summary In recent years opioid use disorder OUD and deaths due to opiate overdose e g with heroin fentanyl oxycodone in suburban and rural non minority groups has created an urgency for approaches to stem this epidemic but the rise in OUD and opiate overdose deaths has occurred in inner cities at similar rates Heroin misuse and addiction are persistent problems in African American communities and in inner cities and a widely understudied trend is that addiction to opioid medication and heroin has become the major cause of morbidity crime and infectious disease in a huge segment of the African American population Despite recent efforts to expand addiction research recruitment to include minorities significant race disparities persist for African Americans and this disparity negatively impacts access to affordable but sophisticated treatment mechanisms available to other groups OUD disrupts reward processing within the mesocorticolimbic system a process that is in part rooted in genetics Our preliminary studies suggest that ancestry specific SNPs may govern addiction behavior in specific groups African Americans express the dopamine receptor DRD A allele at double the frequency of European Americans Moreover pharmacogenomics PGx testing in a cohort of heroin addicts at our facility reveal a significant frequency of the CYP A B allele the variant which confers rapid metabolism of the treatment drug buprenorphine a mu opioid agonist These ancestry specific findings are further corroborated by GWAS studies in drug addicted patients where the intronic SNP in the KAT B Lysine acetyl transferase B gene was specifically identified in African Americans and not in European American addicts Based on this scientific premise we hypothesize that opioid use in African Americans will be associated with hypodopaminergic alleles that alter the threshold for activating feelings of reward and pleasure within the dopaminergic system and that these allelic frequencies will differ significantly from European Americans We propose to develop a targeted system to study genetic risks for reward deficiency using risk gene panel to assign a genetic addiction risk score GARS comprehensive surveys to determine quality of life and exposure to stressors and trauma This system will allow prediction of addiction and relapse potential and delivery of personalized treatment We further propose to develop a dosing strategy for a Neuroadaptogen amino acid therapy NAAT that will reduce the incidence of relapse to opioid use This is a Systematic Medical Approach to Reward Transformation SMART for brain health and opioid use disorders in a mostly African American population in Phase where we will validate the GARS scoring system against PGx data and ethnically and culturally sensitive life situations Assess the effectiveness of the reward system targeted NAAT as an effective treatment to reduce relapse in genetically identified high and low risk groups and Develop a database the SMART Clinical Genomic Registry to facilitate management of clinical social and genomic data This approach promotes brain health even in non opioid users Narrative Opioid Addiction is devastating families across America It is now recognized that effective treatment requires a comprehensive approach inclusive of medically assisted behavioral and cognitive therapy We have developed such a system which will allow for individualized treatment that is culturally and ethnically sensitive to African American lifestyles experiences and genetics a systematic medical approach to reward transformation SMART that will reduce relapse in addicted individuals but also will improve brain health in general in patients with other hypodopaminergic states and reward deficiencies It is highly adaptable to other ethnic or geographic groups