Instructor Rutgers New Jersey Medical School, New Jersey
Background & Introduction: Clinical response to medications for opioid use disorder (MOUD) varies widely, and treatment selection remains largely empirical. Emerging pharmacogenomic data suggest that the intronic single-nucleotide polymorphism (SNP) rs678849 in the delta-opioid receptor gene (OPRD1) predicts buprenorphine treatment response, particularly among African American patients. Most prior studies have examined structured outpatient cohorts, with limited data from emergency department (ED)–initiated treatment settings.
Methods: We conducted an observational pharmacogenomic study of adults (≥18 years) with DSM-5 opioid use disorder (OUD) who initiated buprenorphine through a university-affiliated Emergency Department–Bridge (ED-Bridge) program. Participants provided informed consent for genomic testing. Blood samples were analyzed for OPRD1 rs678849. Clinical outcomes were assessed via retrospective chart review. The primary outcome was opioid-negative urine drug screen (UDS) within ±2 months of the 6-month post-enrollment timepoint. Odds ratios were calculated to assess the association between rs678849 carrier status and opioid-negative UDS outcomes.
Results: Twenty-one patients enrolled in the pharmacogenomic program; thirteen had UDS data within the predefined follow-up window and were included in the primary analysis. Carriers of the OPRD1 rs678849 variant demonstrated significantly improved outcomes compared with non-carriers. Variant carriers had 24-fold higher odds of opioid-negative UDS at 6 months (OR = 24.0; 95% CI 1.11–518.61; p = 0.043). Among patients with opioid-negative UDS results, 62.5% identified as African American, consistent with prior reports of race-specific effects of rs678849.
Conclusion & Discussion: In a real-world ED-initiated MOUD population, the OPRD1 rs678849 variant was strongly associated with improved buprenorphine treatment outcomes. These findings replicate prior pharmacogenomic studies and extend their relevance to emergency department–based addiction treatment. Pharmacogenetic stratification may offer a pathway toward personalized MOUD selection and reduction of disparities in opioid use disorder outcomes, particularly in populations disproportionately affected by overdose mortality.
References: 1. Crist RC, Clarke TK, Ang A, et al. An intronic variant in OPRD1 predicts treatment outcome for opioid dependence in African Americans. Neuropsychopharmacology. 2013;38:2003-2010.
2. Crist RC, Phillips KA, Furnari MA, et al. Replication of the pharmacogenetic effect of rs678849 on buprenorphine efficacy in African Americans with opioid use disorder. Pharmacogenomics J. 2019;19:260-268.
3. Meaden CW, Mozeika A, Asri R, Santos CD. A review of the existing literature on buprenorphine pharmacogenomics. Pharmacogenomics J. 2021;21(2):128-139. doi:10.1038/s41397-020-00198-1
4. Centers for Disease Control and Prevention. Drug overdose deaths in the United States. Published 2024. Updated July 23, 2024. Accessed April 14, 2025. U.S. Department of Health and Human Services.
5. World Health Organization. Clinical guidelines for withdrawal management and treatment of drug dependence in closed settings. 1st ed. World Health Organization; 2009. Accessed April 14, 2025.
Disclosure(s):
Cynthia Santos, MD: No financial relationships to disclose
Christine Ramdin, PhD: No financial relationships to disclose
Learning Objectives:
Upon completion, participant will be able to describe the association between the OPRD1 rs678849 genetic variant and buprenorphine treatment outcomes in an emergency department–initiated MOUD program.
Upon completion, participant will be able to explain how pharmacogenomic data may inform personalized medication selection for opioid use disorder, particularly in racially diverse populations.
Upon completion, participant will be able to identify ethical and equity considerations when integrating pharmacogenomic testing into addiction treatment and emergency care workflows.
