What you need to know
Methadone and buprenorphine/naloxone are opioid agonist therapies (OAT) used to treat opioid use disorder. Although genetic factors influence an individual’s risk of addiction to non-prescribed opioids, the link between genetic factors and treatment success with OAT needs further study.
To address this, the researchers collected urine samples every two weeks for 24 weeks from 150 study participants who had opioid use disorder. During analysis of participant blood samples, they looked for gene variants involved in methadone metabolism, buprenorphine metabolism, and μ-opioid receptor function a receptor in the brain where methadone and buprenorphine act. They then looked for associations between genetic variants and opioid-free urine screens, which would indicate a greater or lesser chance that the participant was able to stop opioid use. The researchers found that participants who had a gene variant that alters the opioid receptor function, OPRM1 rs1799971 G, and received methadone had lower rates of abstinence than those with the more common OPRM1 rs1799971 AA genotype.
The findings suggest that participants with the G-genotypes were less likely to be abstinent and more likely to drop out of treatment than those with the AA genotype. The researchers concluded that the OPRM1 rs1799971 gene variant might help identify those who would respond better to buprenorphine/naloxone rather than methadone for opioid use treatment.
What is this research about?
Methadone and buprenorphine/naloxone are effective opioid agonist therapies (OAT) for opioid use disorder. But some people don’t achieve the outcomes they hope for. Genetic factors are known to influence a person’s risk of developing opioid use disorder, but there is little research on whether they might influence the likelihood that OAT will be effective.
Researchers investigated whether certain gene variants are associated with treatment outcomes in people receiving methadone or buprenorphine/naloxone for prescription-type opioid use disorder.
What did the researchers do?
The researchers examined people who had previously been randomized to methadone or buprenorphine/naloxone for 24 weeks of daily treatment. They assessed urine samples from each visit (every two weeks) to measure non-treatment opioid levels. They also analyzed samples for gene variants that are known to alter methadone metabolism, buprenorphine metabolism, and μ-opioid receptor function.
What Did the Researchers Find?
In the methadone group, participants who had the OPRM1 rs1799971 AA gene variant were more likely to have opioid-free urine samples compared with participants with the G gene variants. Participants in the methadone group who had G variants also had fewer opioid-free urine samples than those in the buprenorphine group with AA or G-gene variants.
These findings suggest that people with opioid use disorder with the OPRM1 rs1799971 G-gene variants may have better treatment results if they receive a different medication (eg, buprenorphine/naloxone) instead of methadone.
Participants in the methadone group who were still in the study after 24 weeks were more likely to have remained abstinent from non-treatment opioids compared to the group in the buprenorphine/naloxone group. This finding is consistent with previous research.
Participants in the methadone treatment subgroup with the OPRM1 rs1799971 G gene variant were less likely to stay in the study and less likely to have remained abstinent by week 24 of the study compared to those with the AA genotype. This finding suggests that the poorer treatment success with methadone seen in those with G-genotypes may be partly due to their having stopped their treatment.
The researchers concluded that, if replicated, the findings would support the potential use of genetic variants when selecting OAT.
Limitations of the Research
The researchers reported some study limitations. Many participants dropped out of the study, and there were fewer opioid-free screening results than the researchers had expected. The small numbers in each treatment arm/genotype group make it hard to be able to say with certainty that the results would be the same in a real-world setting.
In addition, the small number of study participants who were not White makes it difficult to generalize the findings to these groups.
How Can You Use This Research?
While these are early findings, this study provides evidence that pharmacogenetics (the study of how genes affect a person's response to drugs) could be used for selecting an OAT for people with opioid use disorder. It also supports the use of OPRM1 rs1799971 as an objective measure to identify people who might be most likely to benefit from buprenorphine/naloxone rather than methadone.
About the Researchers
Intishar Kazi,1,2 Meghan J. Chenoweth,1,2,3 Didier Jutras-Aswad,4,5 Keith Ahamad,6,7 M. Eugenia Socias,6,8 Bernard Le Foll,1,2,3,9,10,11,12,13 and Rachel F. Tyndale1,2,3
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
- Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada.
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
- Research Centre, Centre Hospitalier de l’Université de Montréal, Montréal, Quebec, Canada.
- Department of Psychiatry and Addictology, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada.
- British Columbia Centre on Substance Use, Vancouver, British Columbia, Canada.
- Department of Family Practice, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
- Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada.
- Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.
- Addictions Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
- Waypoint Research Institute, Waypoint Centre for Mental Health Care, Penetanguishene, Ontario, Canada.