Matthew J. Carpenter

Background and aims: Cigarette smoking is detrimental to oral health. Oral health professionals rarely prescribe smoking cessation medications. Nicotine replacement therapy sampling (NRTS), providing brief starter courses of NRT, could improve provision of NRT and promote cessation. The aim of the Free Samples for Health (FreSH) study was to test the effectiveness of NRTS compared with enhanced usual care on long‐term abstinence from combustible tobacco. Design: Two‐group, pragmatic, cluster (dental practice) randomized clinical trial. Setting: The study was conducted in the Midwest and Northeast nodes of the United States' National Dental Practice‐Based Research Network in 59 dental practices. Practices were randomized to intervention condition. Participants: Participants (recruited June 2023–June 2025) were adult patients of network practices who smoke cigarettes daily [ n = 1196; NRTS n = 486, comparison group (ET) n = 710; 59% female; 71% White]. Intervention and comparator: All participants received Ask‐Advise‐Refer: oral health practitioners asked smoking status, advised quitting and referred to state tobacco quitlines. Participants in the NRTS group were given a 2‐week supply of 14 mg nicotine patches and 4 mg nicotine lozenges; participants in the ET group were given an electric toothbrush. Measurements: Participants were surveyed after their visit and at 1, 3 and 6 months post enrollment. The primary outcome was 7‐day point‐prevalence abstinence measured 6 months post enrollment confirmed via expired breath carbon monoxide (CO) < 6 p.p.m. Secondary outcomes included quit attempts, short‐term abstinence, NRT and quitline use. Covariates included stage of change, confidence, readiness and cigarettes per day. Results: While there was no condition effect on CO‐confirmed abstinence at 6 months post intervention [NRTS: 8.4%, ET: 8.0%; adjusted odds ratio (aOR) = 1.04, 95% confidence interval (CI) = 0.65–2.09], the NRTS intervention statistically significantly increased NRT use across all timepoints (NRTS: 50%, ET: 13%; aOR = 7.39, 95% CI = 5.29–10.31) and quit attempts at all timepoints (NRTS: 58%, ET: 49%; aOR = 1.46, 95% CI = 1.06–2.02). There was a statistically significant effect of NRTS on self‐reported 7‐day point‐prevalence abstinence at 1 month post enrollment (NRTS: 12.8%, ET: 9.0%; aOR = 1.72, 95% CI = 1.03–2.88). There was no difference in quitline use. Practices assigned to the NRTS condition recruited notably fewer participants ( t = 2.11, P = 0.04). Summary: Free nicotine replacement therapy (NRT) samples are not sufficient to improve long‐term smoking abstinence in dental patients; however, NRT samples increase engagement with quitting behaviors and may serve as a starting point toward quitting. Low recruitment in the NRT sampling group demonstrates discomfort by oral health practitioners in discussing smoking among those not voicing readiness to quit.

Importance: Smoking cessation interventions could ultimately offer greater impact to the extent that they are brief, concrete, and face valid (to the individuals presenting and receiving the intervention), which would then make these interventions scalable across a broad spectrum of adults who smoke (AWS). Medication sampling is one potential strategy to meet that need. Objective: To determine outcomes of varenicline sampling in a fully powered randomized clinical trial (RCT), conducted from February 2021 to April 2025. Design, Setting, and Participants: This decentralized RCT included non–treatment seeking AWS with varying levels of motivation to quit who were recruited throughout South Carolina. Intervention: Participants were randomized to receive a 4-week sample of varenicline, nicotine replacement therapy (NRT; active control), or quitline referral (inactive control) in a 2:1:1 ratio. Accompanying 4-week medication supply, intervention messaging in both sampling groups emphasized naturalistic use, ie, a participant-driven experience with self-determined uptake, use, and goals for use. Main Outcomes and Measures: The primary outcome was self-reported 7-day point prevalence abstinence (PPA) at 6-month follow-up. Secondary outcomes included carbon monoxide (CO)–verified abstinence, floating abstinence (any 7-day period of not smoking throughout follow-up), quit attempts, and smoking reduction. Results: The study sample included 651 AWS (mean [SD] age, 52 [11] years; 431 (66%) female), with 161 randomized to the no-sampling control, 172 randomized to NRT, and 318 randomized to varenicline. Compared with the no-sampling control, AWS receiving varenicline samples had higher rates of self-reported PPA at month 6 (16 of 161 [10%] vs 53 of 318 [17%]; P = .048), floating abstinence throughout follow-up (33 [20%] vs 108 [34%]; P = .003); and greater incidence of 50% or greater reduction in cigarettes per day (CPD) by 6 months (31 [19%] vs 106 [33%]; P = .002); however, rates of CO-verified abstinence at 6 months were not significantly different. Varenicline sampling was superior to NRT sampling for 6-month self-reported abstinence (53 [17%] vs 14 of 172 [8%]; P = .01); floating abstinence through 6 months (108 [34%] vs 43 [25%]; P = .04); and incidence of 50% or greater reduction in CPD at week 8 (111 [35%] vs 38 [22%]; P = .005) but not at 6 months. Conclusions and Relevance: In this RCT of 651 AWS, varenicline sampling was efficacious, with potentially superior outcomes compared with NRT. Results provide additional evidence in support of medication sampling as a pragmatic option to engage AWS in cessation, worth further evaluation within an applied settings. Trial Registration: ClinicalTrials.gov Identifier: NCT04525755

Background and aims: Tobacco‐cannabis co‐use is associated with increased psychosocial and health harms; however, the treatment literature assessing the impact of co‐use has been mixed and suffers from critical limitations. To date, no prospective studies have evaluated the degree to which cannabis co‐use affects tobacco cessation, nor are there treatment recommendations for those who co‐use. The goal of this study was to evaluate and quantify the impact of cannabis co‐use on tobacco cessation through a 12‐week prospective tobacco cessation trial. Design: This was a multi‐site, non‐randomized trial. Inverse probability weighted modified Poisson regression models were used to assess the probability of tobacco abstinence between tobacco‐only and tobacco‐cannabis co‐use cohorts. Setting: Enrollment occurred at three sites across South Carolina, USA: The Medical University of South Carolina (MUSC) Charleston, Behavioral Health Services of Pickens County and MUSC Florence. Participants: Enrolled participants were adults ( n = 181; ages 18–40) who (1) smoked tobacco cigarettes and used cannabis regularly (co‐use cohort; oversampled) or (2) smoked tobacco cigarettes daily (tobacco‐only cohort). Across 3 sites, 181 adults (110 co‐using cannabis; 71 tobacco‐only) were enrolled (49% female; 19% Black/African American; 6% Hispanic/LatinX). Interventions: All participants received 12 weeks of first‐line tobacco treatment (varenicline, incentives for tobacco abstinence, counseling), while cannabis use was not addressed as part of treatment. Measurements: The primary outcome was biochemically confirmed 7‐day point prevalence tobacco abstinence (PPA) at end of treatment (EOT; Week 12 post‐enrollment). Findings: Average baseline reported cigarettes per day were not different between tobacco‐only or cannabis co‐use cohorts [14.9, (standard deviation, SD = 7.2) versus 13.4 (SD = 7.8); P = 0.25]. Among the co‐use cohort, days of cannabis use in the past month at baseline was 23.7 (SD = 9.5). In imputed analyses, EOT 7‐day PPA tobacco abstinence was achieved in 59% of tobacco‐only participants and 33% of the cannabis co‐use cohort [Imputed data: relative risk (RR) = 1.63, 95% confidence interval (CI) = 1.14–2.33]. Neither baseline daily cannabis use [adjusted relative risk (RR _adj ) = 1.05, 95% CI = 0.63–1.77] nor within‐treatment cannabis use frequency (RR _adj = 0.51, 95% CI = 0.25, 1.06) was associated with EOT PPA for tobacco in the cannabis co‐use cohort. Conclusions: This is the first prospective study designed to compare tobacco cessation outcomes by cannabis co‐use status. Regular cannabis co‐use had a negative impact on tobacco abstinence among younger to middle‐aged adults. Addressing cannabis use should be incorporated into standard tobacco treatment to improve cessation outcomes.

Introduction: Multiple tobacco product use has increased markedly in the United States, especially dual use of cigarettes and e-cigarettes among young adults. Little is known regarding nicotine replacement therapy (NRT) for young adult dual users, or whether to recommend quitting versus continuing e-cigarettes during smoking cessation treatment. Methods: This 2 × 2 factorial trial randomized 396 young adult dual users (aged 18–29; ≥ 5 cigarettes/day; used e-cigarettes on ≥ 10 of past 30 days) to receive 12 weeks of combination NRT versus No NRT to quit smoking, plus text-based treatment recommendations to Quit versus Continue E-cigarettes. The primary outcome was self-reported end-of-treatment 7-day point-prevalence abstinence (PPA) from cigarettes; a secondary outcome was end-of-treatment 30-day PPA from cigarettes. Results: Participants were 26.0 (SD = 6.8) years old, 52.8% female, and 26.5% non-white. At week 12, NRT increased 7-day PPA (NRT = 50.5% versus No NRT = 39.9%; OR = 1.54, 95% CI = 1.03, 2.29), but neither treatment recommendation (Quit E-cigarettes = 48.0% versus Continue E-cigarettes = 42.4%; OR = 1.25, 95% CI = 0.84, 1.85) nor the NRT-by-treatment recommendation interaction were significant. The direction and magnitude of main effects for 30-day PPA at week 12 were similar to 7-day PPA, but the NRT-by-treatment recommendation interaction was significant (p = .04): smoking cessation was greatest for the NRT plus Quit E-cigarettes condition (47.1%) versus NRT plus Continue E-cigarettes (28.1%); No NRT plus Quit E-cigarettes (29.2%); and No NRT plus Continue E-cigarettes (30.4%) conditions (all p < .05). Conclusions: NRT is effective in promoting early smoking cessation among young adult dual users. Secondary findings indicate that pairing NRT with support to quit both products could enhance the effects on prolonged cigarette abstinence.

People who undergo lung cancer screening (LCS) and continue to smoke are at risk for negative clinical outcomes and lowered survival and need effective smoking cessation interventions. This pilot study tested an 8-week intervention for smoking cessation after LCS. The participants (N = 40) were randomized to the intervention group (combination nicotine replacement therapy [NRT] plus gain-framed text messaging for 8 weeks) or the control group (standard cessation counseling) after LCS. Assessments were completed at 8-week and 3-month follow-ups, including self-reported 7-day point prevalence abstinence. The mean age was 64.4 years old (SD = 6.2); 32.5% were Black or African American; and 55% were female. At Week 8, 14.3% (3/21) of the participants in the intervention group were abstinent versus 0% (0/19) in the control group (p > 0.05). At 3-month follow-up, 4.8% (1/21) of the participants in the intervention group were abstinent versus 0% (0/19) in the control group. Among the intervention group participants, up to 52.4% used the provided patches and up to 61.9% used the provided lozenges during the study period. This study demonstrated modest quit rates for LCS patients receiving gain-framed text messages and NRT. The results highlight the need for more effective smoking cessation interventions for this priority population.

Introduction: The pattern and trajectory of dual use are critical to differentiating it as a health benefit versus harm. Methods: Based within a large, naturalistic randomized controlled trial of e-cigarette in the United States, adults who smoke were given a 1-month sample of tank-style e-cigarette to use as they wish (n = 427) or not (n = 211). Analyses are restricted to participants from the e-cigarette group who became dual users by one month (DU; n = 315) versus participants in control group who exclusively used combustible cigarettes (EUCC; n = 182). Primary outcomes are based on changes in combustible cigarette smoking (cigarettes per day; CPD) across daily diaries within sampling period, and at 3- and 6-month follow-up. Results: DUs reported significantly more diary days of large smoking reduction (smoking 1–50% of baseline CPD: 23.1% of all diary days) and not smoking (5.6% of all diary days) than did EUCCs (6.8% and 1.4%, respectively) during sampling period (ps < .001). Among DUs, 18.4% reported smoking 1–50% of baseline CPD and 9.5% were not smoking at Week 12; 17.5% reported smoking 1–50% of baseline CPD and 9.2% were not smoking at Week 24. In contrast, among EUCCs, 7.1% reported 1–50% of baseline CPD at Week 12 and 1.7% were not smoking. At Week 24, 8.2% reported 1–50% of baseline CPD and 7.1% were not smoking. Among DUs, e-cigarette use days were associated with greater probability of non-smoking days (8%) than non-e-cigarette use days (3%, p < .001). Conclusion: Compared to continued cigarette smoking, initiating dual use reduced smoking and increased cigarette-free days.

Introduction: Genetic studies of smoking cessation have been limited by short-term follow-up or cross-sectional design. Within seven genes (CHRNA3, CHRNA5, CHRNB2, CHRNB4, DRD2, DBH, and CYP2A6) influencing biological mechanisms relevant to smoking, this study aimed to identify single nucleotide polymorphisms (SNPs) associated with smoking cessation throughout up to 38 years of follow-up. Aims and Methods: Participants were from two all-female cohort studies, Nurses’ Health Study (NHS) (n = 10 017) and NHS-2 (n = 2793). For 132 SNPs providing coverage of these genes, genotype associations with the probability of quitting smoking over time were evaluated using generalized estimating equations models. For SNPs reaching nominal statistical significance (p < .05) within NHS, NHS-2 was used as the replication cohort to control for multiple testing (false discovery rate [FDR] < 0.05). SNP genotype by smoking intensity (lifetime light vs. non-light smoking) interactions were also evaluated. Results: Five SNPs identified in NHS were replicated in NHS-2 with FDR < 0.05. Women with the minor alleles of CHRNA5 SNPs rs637137 (odd ratio [OR] = 1.21) and rs503464 (OR = 1.24) had increased odds of cessation. Women with the minor alleles of CYP2A6 SNPs rs56113850 (OR = 0.81) and rs56267346 (OR = 0.82) and DBH SNP rs6479643 (OR = 0.78) had lower odds of cessation throughout adulthood. An interaction with smoking intensity was indicated for three SNPs, CHRNB4 rs4887074, CHRNA3 SNP rs77438700, and CHRNA5 SNP rs76474922. Conclusion: Genetic associations with smoking cessation over decades of follow-up were observed and may guide targeted approaches for smokers most at risk for long-term relapse. Implications: This study identified single nucleotide polymorphisms within CHRNA5-A3-B4, CYP2A6, and DBH that were associated with smoking cessation in women over decades of follow-up. This study is the first to examine these genetic associations over years of follow-up. Some associations were novel while others replicated previous findings from short-term studies for the first time. Potential differences in some associations between light and non-light smokers were also observed. Genetic factors associated with long-term smoking behavior may help inform interventions modeled on long-term chronic disease management approaches; specifically, targeted maintenance interventions to sustain abstinence could be implemented among high-risk smokers.