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PSU increases the risk of negative health consequences, including infectious diseases, worsening physical and mental health conditions, and overdose-related deaths. These consequences occur in the context of varying health risk behaviours, substance-related preferences, and treatment engagements among people with PSU. To inform improvements in prevention, harm reduction, and substance use disorder (SUD) treatment, additional research is needed to comprehensively understand the current context and drivers of PSU preferences, motivations, and behaviours.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Herein, we describe the protocol for a prospective cohort study designed to capture detailed patterns, profiles, and trajectories of PSU, with the aim of comprehensively examining the drivers of PSU behaviours and SUD treatment utilisation. Adults (ages 18\u201375; n=400) who engage in PSU will be recruited from healthcare institutions, an established participant database maintained by an adjacent SUD research team, and online advertisements. Study assessments will capture dynamic patterns, choice preferences, and motivators of PSU via behavioural economic (BE) measures, detailed Timeline Follow-Back (TLFB) interviews, and self-administered surveys. The assessment timeline will include a baseline survey and TLFB interview, weekly TLFB interviews for 4\u2009weeks post-baseline, and follow-up surveys and TLFB interviews at 4-, 8-, and 12-months post-baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study is funded through the National Institutes of Health Helping to End Addiction Long-term (HEAL) initiative and was approved by the University of Michigan Medical Institutional Review Board. Findings will be disseminated to academic, clinical, and community partners through the Michigan Innovations in Addiction Care through Research and Education programme. Results from this study will inform actionable and practical insights relevant to the delivery of personalised care in the context of PSU.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-107600","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T12:25:33Z","timestamp":1765369533000},"page":"e107600","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Preferences and predictors driving opioid-involved polysubstance use profiles and trajectories: a prospective cohort study protocol"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6512-1563","authenticated-orcid":false,"given":"Maya","family":"Campbell","sequence":"first","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josephine I","family":"Lafayette","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina","family":"Vallejo Vasquez","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ava","family":"Rivard","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordan","family":"Diamond","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarence","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominick","family":"Caputo","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahana","family":"Lothumalla","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chavez R","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devin C","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin E","family":"Bonar","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason E","family":"Goldstick","sequence":"additional","affiliation":[{"name":"Injury Prevention Center, University of Michigan, Ann Arbor, Michigan, USA"},{"name":"Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen","family":"Walton","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sunghee","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute for Social Research (ISR), University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Menke","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lewei (Allison)","family":"Lin","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"},{"name":"Center for Clinical Management Research (CCMR), VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara N","family":"Coughlin","sequence":"additional","affiliation":[{"name":"Addiction Center, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"2026010703463412000_15.12.e107600.1","doi-asserted-by":"crossref","unstructured":"Garnett M , Mini\u00f1o A . 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