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Genetic factors contribute to individual differences in opioid response; however, little is known regarding genetic associations with clinical outcomes in people receiving opioid agonist therapies. Participants diagnosed with opioid use disorder, principally consisting of prescription opioids (licit or illicit), were randomized to methadone or buprenorphine\/naloxone for 24\u2009weeks of daily treatment (NCT03033732). Urine was collected at 12 biweekly study visits and analyzed for non\u2010treatment opioids. Variants in genes involved in methadone metabolism (<jats:italic>CYP2B6<\/jats:italic>, <jats:italic>CYP2C19<\/jats:italic>, and <jats:italic>CYP3A4<\/jats:italic>), buprenorphine metabolism (<jats:italic>CYP3A4<\/jats:italic> and <jats:italic>UGT2B7<\/jats:italic>), and \u03bc\u2010opioid receptor function (<jats:italic>OPRM1<\/jats:italic>) were genotyped and analyzed for their association with the number of non\u2010treatment opioid\u2010free urine screens. Primary analyses focused on the last 12\u2009weeks (6 study visits, post\u2010titration) of treatment among those reporting White ethnicity. Additional sensitivity and exploratory analyses were performed. Among methadone\u2010treated participants (<jats:italic>n<\/jats:italic>\u2009=\u200952), the <jats:italic>OPRM1<\/jats:italic> rs1799971 AA genotype (vs. G\u2010genotypes, i.e., having one or two G alleles) was associated with greater opioid\u2010free urine screens (incidence rate ratio\u2009=\u20095.24, 95% confidence interval (CI)\u2009=\u20092.43\u201311.26, <jats:italic>P<\/jats:italic>\u2009=\u20090.000023); longitudinal analyses showed a significant genotype\u2010by\u2010time interaction over the full 24\u2009weeks (12 study visits, \u03b2\u2009=\u2009\u22120.28, 95% CI\u2009=\u2009\u22120.45 to \u22120.11, <jats:italic>P<\/jats:italic>\u2009=\u20090.0015). Exploratory analyses suggest an <jats:italic>OPRM1<\/jats:italic> rs1799971 genotype effect on retention. No evidence of association was found between other genetic variants, including in metabolic variants, and non\u2010treatment opioid\u2010free urine screens in the methadone or buprenorphine\/naloxone arms. Those with the <jats:italic>OPRM1<\/jats:italic> rs1799971 G\u2010genotypes may have a poorer response to methadone maintenance treatment, an effect that persisted through 24\u2009weeks of treatment.<\/jats:p>","DOI":"10.1002\/cpt.3112","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:35:15Z","timestamp":1701131715000},"page":"506-514","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacogenetics of Biochemically Verified Abstinence in an Opioid Agonist Therapy Randomized Clinical Trial of Methadone and Buprenorphine\/Naloxone"],"prefix":"10.1002","volume":"115","author":[{"given":"Intishar","family":"Kazi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Toronto  Toronto Ontario Canada"},{"name":"Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health (CAMH)  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8218-8240","authenticated-orcid":false,"given":"Meghan J.","family":"Chenoweth","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Toronto  Toronto Ontario Canada"},{"name":"Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health (CAMH)  Toronto Ontario Canada"},{"name":"Department of Psychiatry University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Didier","family":"Jutras\u2010Aswad","sequence":"additional","affiliation":[{"name":"Research Centre Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Quebec Canada"},{"name":"Department of Psychiatry and Addictology, Faculty of Medicine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith","family":"Ahamad","sequence":"additional","affiliation":[{"name":"British Columbia Centre on Substance Use  Vancouver British Columbia Canada"},{"name":"Department of Family Practice, Faculty of Medicine University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Eugenia","family":"Socias","sequence":"additional","affiliation":[{"name":"British Columbia Centre on Substance Use  Vancouver British Columbia Canada"},{"name":"Department of Medicine, Faculty of Medicine University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6406-4973","authenticated-orcid":false,"given":"Bernard","family":"Le Foll","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Toronto  Toronto Ontario Canada"},{"name":"Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health (CAMH)  Toronto Ontario Canada"},{"name":"Department of Psychiatry University of Toronto  Toronto Ontario Canada"},{"name":"Dalla Lana School of Public Health University of Toronto  Toronto Ontario Canada"},{"name":"Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute Center for Addiction and Mental Health (CAMH)  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1297-2053","authenticated-orcid":false,"given":"Rachel F.","family":"Tyndale","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Toronto  Toronto Ontario Canada"},{"name":"Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health (CAMH)  Toronto Ontario Canada"},{"name":"Department of Psychiatry University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"Federal provincial and territorial Special Advisory Committee on the epidemic of opioid overdoses opioid\u2010 and stimulant\u2010related harms in Canada. <https:\/\/health\u2010infobase.canada.ca\/substance\u2010related\u2010harms\/opioids\u2010stimulants> (2023)."},{"key":"e_1_2_9_2_1","unstructured":"National Center for Health Statistics U.S.Overdose deaths In 2021 increased half as much as in 2020 \u2013 but are still up 15%. <https:\/\/www.cdc.gov\/nchs\/pressroom\/nchs_press_releases\/2022\/202205.htm> (2022)."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2014.366"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13011-016-0055-4"},{"key":"e_1_2_9_5_1","unstructured":"Health Canada Drug Analysis Service and Cannabis Laboratories. <https:\/\/health\u2010infobase.canada.ca\/drug\u2010analysis\u2010service\/analyzed\u2010drug\u2010report.html> (2023)."},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01709-1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fpc.0000220566.90466.a2"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-018-0513-9"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.11.96"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000437"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3181642938"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0b013e318222b5dd"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2015.08.005"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2166"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.112.193433"},{"key":"e_1_2_9_16_1","first-page":"505","article-title":"Comparative analysis of buprenorphine\u2010 and norbuprenorphine\u2010induced analgesic effects based on pharmacokinetic\u2010pharmacodynamic modeling","volume":"272","author":"Ohtani M.","year":"1995","journal-title":"J. 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