Randomized controlled trial of varenicline to treat tobacco and cannabis co-use.

PROJECT SUMMARY/ABSTRACT The co-use of tobacco and cannabis is prevalent, appears to be increasing among adults in the United States (US), and has been shown to adversely affect treatment and other clinical outcomes. Yet, there are currently no recommended treatment strategies for tobacco-cannabis co-use, nor are there tailored treatment strategies for

tobacco cessation among those who use cannabis. Treatment interventions addressing co-use have been preliminary and none have been designed to evaluate an intervention compared to a control condition through a fully-powered randomized controlled trial. Our preliminary data, supported by the larger literature, has shown

that: 1) cannabis co-use has a profound negative impact on cigarette abstinence, and 2) varenicline, an FDA approved pharmacotherapy for tobacco cessation, may be beneficial in reducing cannabis use. Collectively, our results show promise for varenicline in reducing cannabis use and given its established efficacy for tobacco

cessation, there is strong justification for its evaluation for tobacco-cannabis co-use treatment, as proposed here. We propose to pair a promising pharmacotherapy (varenicline) with psychosocial support targeting co-use in order to bolster treatment outcomes and reduce harms. This study is a completely remote 12-week treatment

trial among adults in South Carolina (ages 18+; N=200) who co-use cigarettes and cannabis regularly. Participants will be included who smoke cigarettes daily or near daily (20+ days in the past 30; other regular tobacco product use is exclusionary) and have used cannabis at least 3 times per week in the past month

(exclusive medical cannabis use is exclusionary). Participants will be randomized 1:1 to varenicline or placebo and both groups will receive an evidence-based psychosocial intervention that includes real-time and asynchronously delivered content (all delivered virtually). The aims of the study are to: 1) evaluate rates of 7-

day biochemically confirmed point prevalence abstinence (PPA) from cigarettes at the 12-week end of treatment (EOT) visit comparing varenicline + psychosocial intervention to the placebo + psychosocial intervention participants (Aim 1), 2) compare cannabis use frequency and amount between varenicline and placebo groups

from the target quit date until EOT (Weeks 1-12; Aim 2), and 3) explore differential treatment outcomes among male vs. female participants (Exploratory Aim). There is an urgent need to evaluate treatment interventions addressing the co-use of tobacco and cannabis in a general population of adults. The proposed intervention is

supported by rigorous prior research, including our own work, and the decentralized design and remote intervention delivery contribute to the scalability of this intervention to address co-occurring tobacco and cannabis use.