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No prospective treatment studies to date have evaluated the impact of cannabis use on nicotine cessation specifically among young adults, with an emphasis on dual-use substance patterns predicting outcomes. The overall goal of this protocol is to characterise the relationship between nicotine and cannabis and evaluate how patterns of co-use are associated with nicotine cessation outcomes through a behavioural economics framework to examine how cannabis co-use may be associated with nicotine cessation. This study protocol describes an ongoing, prospective nicotine cessation trial being conducted among young adults who co-use nicotine (vaping and\/or cigarettes) and cannabis products to: (1) evaluate the association between behavioural economically derived measures of substance substitutability on end of treatment (EOT) nicotine abstinence, (2) examine whether changes in nicotine use are associated with changes in cannabis demand and use and (3) assess reciprocal prospective relationships between patterns of nicotine and cannabis use during treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a fully remote, prospective, 12-week nicotine cessation trial among young adults (ages 18\u201325; target N=350) across the USA who co-use nicotine and cannabis. Eligible participants vape nicotine and\/or smoke cigarettes regularly (20+ days in the past 30) and use cannabis on 10+ out of the past 30 days. Participants receive comprehensive nicotine cessation treatment, which includes digital contingency management to reinforce nicotine abstinence, brief counselling and SMS-text based cessation support whereas cannabis use is monitored but not treated. Biochemical verification (through oral fluid samples) and self-reports (mobile daily diaries) of substance use are collected longitudinally. Study enrolment began in May 2024 and is expected to conclude in September 2027.<\/jats:p>\n                    <jats:p>Aim 1 (primary outcome) analyses will evaluate whether baseline behavioural economic indices of nicotine\u2013cannabis substitutability predict EOT nicotine abstinence using logistic regression models. Aim 2 (exploratory outcome) analyses will use generalised linear mixed-effects models to examine within-person associations between changes in nicotine use (abstinence, reduction in use, nicotine withdrawal) and cannabis demand and use over time, and whether these associations are moderated by time-varying substitutability. Cross-lagged panel models will be used for Aim 3 (exploratory outcome) to assess reciprocal prospective relationships between nicotine and cannabis use during treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study has received Institutional Review Board approval from the Medical University of South Carolina (reference ID: Pro00131124). All participants provide informed consent prior to study procedures. Findings will be disseminated through peer-reviewed publications, conference presentations and data sharing in accordance with National Institutes of Health and institutional guidelines. The manuscript reports protocol components according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06239350\">NCT06239350<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-110992","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:20:21Z","timestamp":1784290821000},"page":"e110992","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating cannabis\u2013nicotine substitution and demand during nicotine cessation treatment in young adults: protocol for a prospective, remote 12-week nicotine cessation trial in the USA"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct06239350","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06239350","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06239350","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06239350","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9399-0012","authenticated-orcid":false,"given":"Ashley N","family":"Dowd","sequence":"first","affiliation":[{"name":"Medical University of South Carolina Department of Psychiatry and Behavioral Sciences, Charleston, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel L","family":"Baker","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina Department of Public Health Sciences, Charleston, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7923-7734","authenticated-orcid":false,"given":"Mikhail N","family":"Koffarnus","sequence":"additional","affiliation":[{"name":"University of Kentucky Department of Family and Community Medicine, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany R","family":"Raiff","sequence":"additional","affiliation":[{"name":"Department of Psychology, Rowan University, Glassboro, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel L","family":"Tomko","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina Department of Psychiatry and Behavioral Sciences, Charleston, South Carolina, USA"},{"name":"Medical University of South Carolina Hollings Cancer Center, Charleston, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M","family":"Gray","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina Department of Psychiatry and Behavioral Sciences, Charleston, South Carolina, USA"},{"name":"Medical University of South Carolina Hollings Cancer Center, Charleston, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin A","family":"McClure","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina Department of Psychiatry and Behavioral Sciences, Charleston, South Carolina, USA"},{"name":"Medical University of South Carolina Hollings Cancer Center, Charleston, South Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"2026071705201232000_16.7.e110992.1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6946a4"},{"key":"2026071705201232000_16.7.e110992.2","doi-asserted-by":"crossref","unstructured":"Johnston LD , Miech RA , O\u2019Malley PM , et al . 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