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Clinical Trial
. 2025 Jun 3;333(21):1876-1886.
doi: 10.1001/jama.2025.3810.

Varenicline for Youth Nicotine Vaping Cessation: A Randomized Clinical Trial

A Eden Evins  1   2 , Corinne Cather  1   2 , Harrison T Reeder  2   3 , Bryn Evohr  1 , Kevin Potter  1   2 , Gladys N Pachas  1   2 , Kevin M Gray  4 , Sharon Levy  2   5 , Nancy A Rigotti  2   6 , Vanessa Iroegbulem  1 , Jason Dufour  1 , Kelly Casottana  1 , Meghan A Costello  1   2 , Jodi M Gilman  1   2 , Randi M Schuster  1   2
Affiliations
Clinical Trial

Varenicline for Youth Nicotine Vaping Cessation: A Randomized Clinical Trial

A Eden Evins et al. JAMA. .

Abstract

Importance: Electronic cigarette use (vaping) among adolescents and young adults is common. Few treatments have been tested in this population.

Objective: To evaluate the efficacy of varenicline for nicotine vaping cessation in youth who do not smoke tobacco regularly.

Design, setting, and participants: A 3-group randomized clinical trial compared 12 weeks of double-blind varenicline vs placebo, each added to brief, remotely delivered behavioral counseling and compared with single-blind enhanced usual care, with monthly follow-up to 24 weeks. The trial was conducted among youth, aged 16 to 25 years, who vaped nicotine daily or near daily, did not regularly smoke tobacco, and wanted to reduce or quit vaping, in a single US state from June 2022 to May 2024. Data collection ended May 28, 2024.

Interventions: Participants were randomized (1:1:1) to 12 weeks of varenicline titrated to 1 mg twice daily over 7 days (standard titration), weekly counseling, and referral to text messaging vaping cessation support (This is Quitting [TIQ]) (n = 88); identical placebo, weekly counseling, and referral to TIQ (n = 87); or enhanced usual care (referral to TIQ only) (n = 86).

Main outcomes and measures: Biochemically verified continuous vaping abstinence for the last 4 weeks of varenicline treatment vs placebo (primary outcome). Secondary outcomes included bioverified continuous abstinence from weeks 9 through 24 in the varenicline and placebo groups. Additional analyses compared varenicline group and placebo group with enhanced usual care.

Results: Of 261 randomized participants (mean age, 21.4 years; 53% female), 254 completed the trial (97.3%). For varenicline and placebo, continuous abstinence rates were 51% vs 14% during weeks 9 through 12 (adjusted odds ratio [aOR], 6.5 [95% CI, 3.0-14.1]; P < .001) and 28% vs 7% during weeks 9 through 24 (aOR, 6.0 [95% CI, 2.1-16.9]; P < .001). Varenicline had higher continuous abstinence rates vs enhanced usual care during weeks 9 through 12 (51% vs 6%; aOR, 16.9 [95% CI, 6.2-46.3]) and during weeks 9 through 24 (28% vs 4%; aOR, 11.0 [95% CI, 3.1-38.8]). Continuous abstinence rates were not significantly different between the placebo and enhanced usual care groups. Study medication was generally well tolerated. Two varenicline participants (2%) and 1 placebo participant (1%) discontinued study medications due to adverse events. No drug-related serious adverse events occurred. Treatment-emergent adverse events were reported by 76 (86%) in the varenicline group, 68 (79%) in the placebo group, and 68 (79%) in the enhanced usual care group.

Conclusions and relevance: Varenicline, combined with behavioral counseling, increased vaping abstinence in youth who vape nicotine and do not regularly smoke tobacco.

Trial registration: ClinicalTrials.gov Identifier: NCT05367492.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Evins reported receiving a grant from Charles River Analytics (subcontract for a National Institute on Drug Abuse [NIDA] grant) outside the submitted work. Dr Cather reported receiving a grant from Charles River Analytics (subcontract for a NIDA grant) and receiving consulting fees from Navigate. Dr Pachas reported serving on the Racial Equity Advisory Board and the Scientific Advisory Board for the Massachusetts Department of Public Health Bureau of Substance Abuse Services outside the submitted work. Dr Gray reported receiving consulting fees from Achieve Life Sciences and Indivior and receiving grants from Aelis Farma outside the submitted work. Dr Levy reported previously serving as an expert witness in legal cases against JUUL. Dr Rigotti reported receiving grants from Achieve Life Sciences regarding vaping cessation; receiving personal fees from Achieve Life Sciences ending in 2022; and receiving personal fees from Wolters Kluwer for writing UpToDate reviews of smoking cessation and electronic cigarettes outside the submitted work. Dr Iroegbulem reported grants from NIH outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Screening, Randomization, and Follow-Up of Trial Participants in the Study of Varenicline Added to Behavioral Treatment and Text Messaging Support for Vaping Cessation in Youth
aRandomization was 1:1:1 between varenicline (titrated to 1 mg twice daily over 7 days [standard titration], behavioral counseling, and text messaging support), placebo (placebo, behavioral counseling, and text messaging support), and enhanced usual care (text messaging support only) and was stratified by secondary school status (currently in secondary school vs postsecondary school).
Figure 2.
Figure 2.. Longitudinal Observations of Nicotine Vaping Abstinence Rates and Nicotine Withdrawal, Craving, and Distress, by Treatment Intervention Group
Panel tables show number of observed outcome measures at each study visit. A, Abstinence rates and Wilson 95% confidence intervals (vertical lines) computed by visit among observed participants. Participants with self-reported abstinence missing bioverification treated as missing. B-D, Means and Wald 95% confidence intervals (vertical lines) computed by visit among observed participants. See Table 1 footnotes for explanations of scale interpretations.
See this image and copyright information in PMC

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