The purpose of this study is to better understand tobacco outcomes using a commonly prescribed stop smoking medication (varenicline) and financial incentives for adults who also use cannabis. Varenicline is not FDA approved for e-cigarette cessation, but is FDA approved for cigarette cessation. Investigators are also interested in how cannabis/marijuana and tobacco interact during a tobacco quit attempt. All participants will receive e-cigarette cessation treatment for 12 weeks. To qualify, participants must be between the ages of 18-40 and use both e-cigarettes and cannabis. Participants do not need to be interested in quitting cannabis to qualify. This study is being conducted at three sites: the Medical University of South Carolina in Charleston, SC, Behavioral Health Services in Pickens, SC, and MUSC Lancaster in Lancaster, SC.

Cannabis co-use among tobacco users is exceedingly common and rates of co-use appear to be increasing among adults in the US, which is consistent with overall increases in cannabis use rates among US adults. Given the current cannabis landscape, further increases in cannabis use are likely and may result in continued increases in the co-use of cannabis and tobacco.

Despite high rates of co-use, there is little consensus regarding treatment recommendations for this population and an understanding of the impact of co-use on successful cessation. The literature on the impact of co-use on tobacco cessation outcomes specifically has been mixed and fraught with limitations, including methodological variation, lack of biochemical verification to confirm cannabis use status and severity, and variations in study samples. Currently, no prospective studies have been conducted to evaluate the impact of cannabis use on tobacco cessation outcomes. Further, no studies have collected cannabis use changes during tobacco cessation treatment to assess for concurrent reductions, abstinence, or of greater concern, compensatory (i.e., increased) use as a result of tobacco reduction/abstinence.

This study is a prospective 12-week tobacco cessation trial using established methods and outcomes typical of tobacco cessation trials, but specifically recruiting co-users of cannabis. The aims of this proposed study are to; Specific Aim 1. Compare rates of 7-day biochemically-confirmed e-cigarette abstinence with cigarette abstinence rates from the parent R37 co-use sample (as a historical controls). Specific Aim 2. Assess changes in cannabis use during e-cigarette cessation treatment among the new sample of participants enrolled in this extension.

Specific Aim 3. Assess for a dose-dependent impact of cannabis co-use severity on e-cigarette cessation. Specific Aim 4. Characterize and compare patterns of co-use among the e-cigarette sample to those using cigarettes (parent R37).

Inclusion Criteria:

• Between the ages of 18 and 40 years old
• Use e-cigarettes daily or near daily in the past month
• Must submit a positive instant-read urine cotinine test at screening (≥ 200 ng/ml)
• Be interested in quitting use of e-cigarettes
• Must be willing to take varenicline for the standard 12-week course of treatment
• Self-reported use of cannabis on at least 10 out of the past 30 days or must submit a positive qualitative urinary cannabinoid test at screening (> 50 ng/ml)

Exclusion Criteria:

• Any serious or unstable medical/psychiatric disorder (including severe substance use disorders, other than cannabis or tobacco use disorders) in the past three months that may interfere with study performance
• Use of cigarettes on 10+ days in the past 30
• Currently pregnant or breastfeeding
• Current use of medications with smoking cessation efficacy
• Use of any medications that would interfere with varenicline

De-identified data will be made available for retrieval and analysis of secondary outcomes, upon request to the Principal Investigator. Study datasets (de-i