ABSTRACT
Pharmacogenetic investigations into the opioid crisis suggest genetic variation could be a significant cause of opioid-related morbidity and mortality. Variability in opioid system genes, including single nucleotide polymorphisms, manifest after pharmacogenetic testing, as previously invisible risk factors for addiction and overdose. Pharmacodynamic genes regulate opioid-sensitive brain networks and neural reward circuitry. Pharmacokinetic genes expressed in drug metabolic pathways regulate blood levels of active vs. inactive opioid metabolites. Elucidating the complex interplay of genetic variations in pharmacokinetic and pharmacodynamic pathways will shed new light on the addictive and toxic properties of opioids. This narrative review serves to promote understanding of key genetic mechanisms affecting the metabolism and actions of opioids, and to explore causes of the recent surge in opioid-related mortality associated with COVID-19. Personalised treatment plans centred around an individual's genetic makeup could make opioid-based pain management and opioid use disorder (OUD) treatments safer and more effective at both the individual and system levels.