A multi-site study examining the tobacco withdrawal trajectory in people with tobacco and cannabis co-use

Background: Approximately 30 % of people who use tobacco also use cannabis, and rates of co-use are rising. Relative to people who use tobacco alone (TO), individuals who co-use tobacco and cannabis (TC) experience greater difficulty with tobacco cessation, yet mechanisms underlying this phenomenon remain unexplored. Leveraging data from a multi-site, double-blind clinical trial for tobacco cessation, we compared the trajectory of tobacco withdrawal, a strong predictor of relapse, between TC and TO during 11-weeks of tobacco treatment. Methods: People seeking treatment for tobacco were randomized to one of three arms (placebo, nicotine patch or varenicline) and followed for 11-weeks. Participants were parsed according to their cannabis use status determined by a cannabis-positive urine toxicology at screen (N = 1246). We selected participants with end-of-treatment biochemically verified 7-day point prevalence tobacco abstinence (N = 330; TC, n = 55 and TO, n = 275) and examined group differences in tobacco withdrawal severity using the Minnesota Nicotine Withdrawal Scale (MNWS) at baseline, week 1, 4, 8, and week 11 (end-of-treatment). Results: Controlling for age, treatment arm, and site, we found a significant interaction (group x time) effect for withdrawal severity (p < 0.01). Bonferroni-corrected post-hoc comparisons revealed that relative to TO, TC had elevated withdrawal scores at week 1 (TC, M=9.3 ± 5.5; TO, M=7.1 ± 5.6; p < 0.01); no other timepoints showed between-group differences. Conclusions: People who co-use experience greater tobacco withdrawal severity one-week post abstinence compared to people who only use tobacco. Personalized interventions that target immediate tobacco withdrawal and/or cannabis use may help improve tobacco cessation rates for people who co-use both substances.