New findings have emerged linking single-nucleotide polymorphisms (SNPs) to opioid use. The research, published in Clinical Pharmacology and Therapeutics, identified SNP genetic variants associated with opioid use disorder (OUD) – providing promising prognostic and therapeutic targets in the future.
The scale of opioid use disorder
Drug overdoses, particularly opioid-related overdose, represent a major public health issue. Over 100,000 Americans died from drug overdose in 2021, with deaths involving synthetic opioids increasing more than 20% from the previous year. The cost of opioid-related overdose mortality has been estimated to exceed $1 trillion annually in the USA.
A detailed understanding of the underlying biological pathways is required to address the incidence of OUD. Approximately 30-40% of OUD cases are presumed to have some genetic component. This indicates that genetic markers could be used to identify personal risk of OUD development. However, most research to date has been retrospective and the role of specific genes remains unclear.
Exploring pharmacodynamics and pharmacokinetics
The current study aimed to identify genetic variants associated with OUD. A cross-sectional approach was adopted, including 1,301 participants total, 250 of which were positive for ever having OUD within their lifetime. 180 candidate SNPs were analysed. 120 of these related to pharmacodynamics and the dopamine reward pathway, 60 related to pharmacokinetics (specifically drug metabolism and transport).
First author of the paper, Caroline Freiermuth, stated: “We wanted to determine for any random person who comes to the emergency department what their genetic link might be and do they now or did they ever have opioid use disorder in their life, and do we think their genetics have played a role in that”.
Six SNPs across four genes were found to be associated with OUD. SNPs in the genes CYP3A5 and DRD3 were found to increase risk of OUD, whereas those in CYP3A4 and CYP1A2 were found to decrease the risk of OUD. Looking in more depth, some of the SNPs identified are associated with the dopamine reward pathway, which has been demonstrated to be an incredibly strong driver of behaviour in animal studies.
Pharmacological significance
The results from the study have the potential to impact clinical pharmacology and translational science. The identification of SNPs provides promising prognostic and therapeutic targets related to OUD, that can be progressed in the future. Freiermuth hopes that the results can help to inform opioid prescription, “I think this is really exciting because it should help us try to figure out who is truly at risk when they are exposed to opioids and that could make it easier for us to decide who we can and can’t prescribe opioids to. This could help determine who might need further monitoring in the future instead of just blanket saying ‘nobody should ever get more than a certain amount’.”
