Background and aims: Tobacco-cannabis co-use is associated with increased psychosocial and health harms; however, the treatment literature assessing the impact of co-use has been mixed and suffers from critical limitations. To date, no prospective studies have evaluated the degree to which cannabis co-use affects tobacco cessation, nor are there treatment recommendations for those who co-use. The goal of this study was to evaluate and quantify the impact of cannabis co-use on tobacco cessation through a 12-week prospective tobacco cessation trial.
Design: This was a multi-site, non-randomized trial. Inverse probability weighted modified Poisson regression models were used to assess the probability of tobacco abstinence between tobacco-only and tobacco-cannabis co-use cohorts.
Setting: Enrollment occurred at three sites across South Carolina, USA: The Medical University of South Carolina (MUSC) Charleston, Behavioral Health Services of Pickens County and MUSC Florence.
Participants: Enrolled participants were adults (n = 181; ages 18-40) who (1) smoked tobacco cigarettes and used cannabis regularly (co-use cohort; oversampled) or (2) smoked tobacco cigarettes daily (tobacco-only cohort). Across 3 sites, 181 adults (110 co-using cannabis; 71 tobacco-only) were enrolled (49% female; 19% Black/African American; 6% Hispanic/LatinX).
Interventions: All participants received 12 weeks of first-line tobacco treatment (varenicline, incentives for tobacco abstinence, counseling), while cannabis use was not addressed as part of treatment.
Measurements: The primary outcome was biochemically confirmed 7-day point prevalence tobacco abstinence (PPA) at end of treatment (EOT; Week 12 post-enrollment).
Findings: Average baseline reported cigarettes per day were not different between tobacco-only or cannabis co-use cohorts [14.9, (standard deviation, SD = 7.2) versus 13.4 (SD = 7.8); P = 0.25]. Among the co-use cohort, days of cannabis use in the past month at baseline was 23.7 (SD = 9.5). In imputed analyses, EOT 7-day PPA tobacco abstinence was achieved in 59% of tobacco-only participants and 33% of the cannabis co-use cohort [Imputed data: relative risk (RR) = 1.63, 95% confidence interval (CI) = 1.14-2.33]. Neither baseline daily cannabis use [adjusted relative risk (RRadj) = 1.05, 95% CI = 0.63-1.77] nor within-treatment cannabis use frequency (RRadj = 0.51, 95% CI = 0.25, 1.06) was associated with EOT PPA for tobacco in the cannabis co-use cohort.
Conclusions: This is the first prospective study designed to compare tobacco cessation outcomes by cannabis co-use status. Regular cannabis co-use had a negative impact on tobacco abstinence among younger to middle-aged adults. Addressing cannabis use should be incorporated into standard tobacco treatment to improve cessation outcomes.
Keywords: cannabis; co‐use; intervention; marijuana; prospective; tobacco cessation; treatment; varenicline.
© 2026 The Author(s). Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.