Varenicline is used to treat tobacco use dependence. It helps reduce cravings for tobacco use and decreases the pleasurable effects of cigarettes and other tobacco products. Varenicline has been proven to reduce the desire to smoke cigarettes. This study aims to test whether it shows a similar benefit for individuals who vape and are interested in quitting.

Varenicline is a highly efficacious FDA-approved smoking cessation pharmacotherapy. The aim of this study is to examine the effectiveness of varenicline for e-cigarette cessation medication for mono- e-cigarette use in combination with a minimal, self-guided behavior change booklet. This booklet will include general tips for e-cigarettes cessation and information about the free web-based e-cigarette cessation program sponsored by The Truth Initiative and Mayo called "This is Quitting". This study will have an 8-week treatment period and a 4-week follow-up phase. Participants will be randomized to receive an 8-week supply of varenicline or matching placebo (gel capsule filled with cellulose powder) in combination with the self-change booklet. The investigators hypothesize that participants who receive varenicline will have higher rates of e-cigarette cessation.

Inclusion Criteria:

• daily use of an e-cigarette containing nicotine (defined as use for at least 25 days out of the past month)
• use of an e-cigarette containing nicotine> 6 months
• have desire to quit e-cigarettes, are willing to set a quit date and maintain e-cigarette abstinence
• have daily access to a smartphone or have regular (daily) access/use of email
• live in South Carolina or Connecticut

Exclusion Criteria:

• Vulnerable Populations: Not be enrolling vulnerable populations, specifically pregnant women, children, prisoners, or institutionalized individuals
• The investigators will not enroll participants incapable of providing their own consent. The rationale will be provided to the individual as well as his or her family members.

Referrals for further evaluation, including urgent or emergent evaluation, will be made as needed and clinically warranted.

• exclude individuals with medical contraindications for varenicline use (i.e., severe renal impairment)
• exclude anyone currently using smoking cessation medications.
• Individuals will also be excluded if another household member is currently enrolled in the study.
• Individuals will be excluded if not proficient in English.
• Individuals will be excluded if they have smoked any combustible cigarettes in the past 6 months.
• Verification of Non-Pregnancy: Females ages <55 will be mailed a commercially available pregnancy test to verify non-pregnancy. Written confirmation of negative pregnancy test via REDCap will be required prior to enrollment in the trial. Participants are also informed that they should let us know if they become pregnant during the trial. Medications will not be sent until this verification is in place. These procedures are based on the Medical University of South Carolina Internal Review Board approved STARS protocol.

12 weeks