{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T05:30:45Z","timestamp":1766727045476,"version":"3.48.0"},"reference-count":31,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Research Council of Norway","doi-asserted-by":"crossref","award":["269864"],"award-info":[{"award-number":["269864"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006095","name":"South-Eastern Norway Regional Health Authority","doi-asserted-by":"crossref","award":["2019105"],"award-info":[{"award-number":["2019105"]}],"id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: The variation in the treatment outcomes of extended-release naltrexone (XR-NTX) including the potential role of genetic factors are poorly understood. This study aimed to explore the potential association between the catechol-O-methyltransferase (COMT) rs4680 and mu-opioid receptor (OPRM1) rs1799971 genotypes and XR-NTX treatment outcomes in patients with opioid use disorder (OUD) specifically focusing on treatment retention, relapse to opioids, number of days of opioid use, and opioid cravings. Methods: This was a 24-week, open-label clinical prospective, exploratory study involving patients with OUD who chose treatment with monthly injections of intramuscular XR-NTX. Men and women aged 18\u201365 years with OUD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were included. The participants were interviewed using the European Addiction Severity Index. Survival analyses and linear mixed models were used to analyze the data. Results: Of the 162 participants included in this study, 138 (21% female) initiated treatment with XR-NTX, with 88 genotyped for COMT rs4680 and 86 for OPRM1 rs1799971. Heterozygous Met\/Val carriers of COMT rs4680 were less likely to relapse to opioids compared with those with the COMT rs4680 Met\/Met genotype. No significant association was observed for the OPRM1 polymorphism. Conclusions: Patients with the COMT rs4680 Met\/Val genotype exhibit a reduced risk of relapse to opioids and may therefore derive greater benefit from XR-NTX treatment compared with those with the COMT rs4680 Met\/Met genotype. Future studies should be conducted with a larger number of participants and possibly include other genetic variants and treatment outcomes. The trial is registered at ClinicalTrials.gov (#NCT03647774) and the EU Clinical Trial Register (#2017-004706-18).<\/jats:p>","DOI":"10.3390\/brainsci16010023","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T14:27:51Z","timestamp":1766586471000},"page":"23","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Influence on Extended-Release Naltrexone Treatment Outcomes in Patients with Opioid Use Disorder: An Exploratory Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6522-0473","authenticated-orcid":false,"given":"Farid","family":"Juya","sequence":"first","affiliation":[{"name":"Division of Mental Health and Addiction, Vestfold Hospital Trust, 3103 T\u00f8nsberg, Norway"},{"name":"Faculty of Medicine, University of Oslo, 0313 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4622-2947","authenticated-orcid":false,"given":"Kristin","family":"Klemmetsby Solli","sequence":"additional","affiliation":[{"name":"Division of Mental Health and Addiction, Vestfold Hospital Trust, 3103 T\u00f8nsberg, Norway"},{"name":"Department of R&D in Mental Health, Akershus University Hospital, 1478 L\u00f8renskog, Norway"},{"name":"Norwegian Centre for Addiction Research, University of Oslo, 0313 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3918-8149","authenticated-orcid":false,"given":"Ann-Christin","family":"Sannes","sequence":"additional","affiliation":[{"name":"Department of R&D in Mental Health, Akershus University Hospital, 1478 L\u00f8renskog, Norway"},{"name":"Faculty of Health Sciences, Oslo Metropolitan University, 0176 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1800-7318","authenticated-orcid":false,"given":"Bente","family":"Weimand","sequence":"additional","affiliation":[{"name":"Department of R&D in Mental Health, Akershus University Hospital, 1478 L\u00f8renskog, Norway"},{"name":"Center for Mental Health and Substance Abuse, University of South-Eastern Norway, 3045 Drammen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1292-3465","authenticated-orcid":false,"given":"Johannes","family":"Gjerstad","sequence":"additional","affiliation":[{"name":"Department of R&D in Mental Health, Akershus University Hospital, 1478 L\u00f8renskog, Norway"},{"name":"School of Health Sciences, Kristiania University College, 0107 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4001-6325","authenticated-orcid":false,"given":"Lars","family":"Tanum","sequence":"additional","affiliation":[{"name":"Department of R&D in Mental Health, Akershus University Hospital, 1478 L\u00f8renskog, Norway"},{"name":"Faculty of Health Sciences, Oslo Metropolitan University, 0176 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9868-2450","authenticated-orcid":false,"given":"Jon","family":"Mordal","sequence":"additional","affiliation":[{"name":"Division of Mental Health and Addiction, Vestfold Hospital Trust, 3103 T\u00f8nsberg, Norway"},{"name":"Department of R&D in Mental Health, Akershus University Hospital, 1478 L\u00f8renskog, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1111\/add.14180","article-title":"Extended-release injectable naltrexone for opioid use disorder: A systematic review","volume":"113","author":"Jarvis","year":"2018","journal-title":"Addiction"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1016\/S0140-6736(11)60358-9","article-title":"Injectable extended-release naltrexone for opioid dependence: A double-blind, placebo-controlled, multicentre randomised trial","volume":"377","author":"Krupitsky","year":"2011","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1159\/000501931","article-title":"Availability of Extended-Release Naltrexone May Increase the Number of Opioid-Dependent Individuals in Treatment: Extension of a Randomized Clinical Trial","volume":"25","author":"Solli","year":"2019","journal-title":"Eur. 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