Low Nicotine Content Cigarettes Research Articles

Effects of Very Low Nicotine Content Cigarettes and Nicotine Vaping Device Characteristics on Choices to Smoke, Vape, or Abstain in Early Young Adults.

A national nicotine reduction policy could reduce the public health toll of smoking. However, reducing nicotine in cigarettes may lead to changes in the use of other tobacco products such as nicotine vaping devices, particularly among young people. Product use outcomes may depend on characteristics of available nicotine vaping devices. We aimed to determine the impact of cigarette nicotine content, vaping device nicotine concentration, and vaping device flavors on choices to smoke, vape, or abstain. Early young adults (ages 18-20 inclusive, N=80) who reported smoking daily and vaping nicotine at least twice in their lifetime participated in a laboratory study. Participants received either Very Low Nicotine Content (VLNC; 0.4mg nicotine/g of tobacco) or Normal Nicotine Content (NNC; 15.8mg/g) cigarettes. First, participants chose between their assigned cigarette or abstaining. Subsequently, participants chose between 2 cigarette puffs, 2 vape puffs, or abstaining. Vaping device nicotine concentration (3mg vs. 18mg/ml) and flavor (tobacco vs. non-tobacco) were manipulated within-subjects. When only cigarettes were available, there were no differences between the VLNC and NNC groups on cigarette choices. When the nicotine vaping device was concurrently available, the VLNC group made fewer choices to smoke than the NNC group. Non-tobacco flavors and lower vaping device nicotine concentration were associated with fewer choices to smoke. Nicotine vaping device availability reduced choices to smoke VLNC cigarettes, and vaping devices with lower nicotine and non-tobacco flavors led to the fewest choices to smoke. Regulators should consider that the availability and characteristics of alternative tobacco products can moderate the product standard's impact. The U.S. Food and Drug Administration may enact a reduced nicotine product standard that would affect all commercially-available cigarettes. One important population affected by this policy would be early young adults who smoke. We aimed to determine the impact of cigarette nicotine content, vaping device nicotine concentration, and vaping device flavors on choices to smoke, vape, or abstain. Lower nicotine in cigarettes, along with non-tobacco flavors and lower nicotine concentration in the vaping device, were associated with the fewest choices to smoke. Regulators should consider that the availability and characteristics of alternative tobacco products can moderate the product standard's impact.

Associations between compliance with very low nicotine content (VLNC) cigarettes, abstinence self-efficacy, and quit outcomes in a pilot smoking cessation trial

BackgroundSwitching to Very Low Nicotine Content (VLNC) cigarettes reduces toxicant exposure and nicotine dependence, and may improve smoking cessation. However, non-compliance with VLNCs is often high, which may reduce their effectiveness. Here, we conducted secondary analyses of a pilot smoking cessation trial utilizing VLNCs to examine associations between pre-cessation VLNC compliance and changes in smoking rate, dependence, and abstinence self-efficacy, as well as quit outcomes. MethodsPeople who smoke daily (n=35) engaged in a 4-week pre-cessation intervention including VLNCs, transdermal nicotine patch, and behavioral counseling. After quit date, participants received 8 weeks of nicotine replacement therapy and 4 additional behavioral sessions, and were followed for 10 weeks to assess abstinence. Compliance with VLNCs was assessed biweekly during pre-cessation using timeline follow-back. Statistical analyses examined associations between VLNC compliance and a) changes in smoking rate, dependence and abstinence self-efficacy over the course of study cigarette use; and b) time to relapse, controlling for other smoking variables. ResultsGreater compliance during the second half of study cigarette use was associated with subsequent improvement in self-efficacy (p<.05). Increased self-efficacy and VLNC compliance both predicted lower likelihood of relapse. Nicotine dependence and cigarettes per day both decreased following study cigarette use, but were unrelated to compliance or relapse. ConclusionsCompliance with VLNCs prior to quitting increased abstinence self-efficacy and predicted better quit outcomes above and beyond baseline smoking characteristics. Although preliminary, these findings suggest that identifying strategies to promote exclusive use of VLNCs during a brief pre-cessation window may be beneficial.

Changes in weight among individuals with psychiatric conditions or socioeconomic disadvantage assigned to smoke very low nicotine content cigarettes.

Nicotine abstinence leads to weight gain, which could be an unintended consequence of a nicotine reduction policy. This secondary analysis used weekly assessments of weight and ratings of "increased appetite/hunger/weight gain" collected in three 12-week, randomized controlled trials evaluating the effects of cigarettes differing in nicotine dose (15.8, 2.4, or 0.4 mg/g) among individuals with affective disorders, opioid use disorder (OUD), and socioeconomically disadvantaged women. Linear mixed models tested differences by dose and time. Analyses first collapsed across populations and then separated out individuals with OUD because biomarkers suggested they used substantially more noncombusted nicotine. Across populations, weight increased significantly over time, averaging 1.03 kg (p < .001), but did not vary by dose nor was there any interaction of dose/time. "Increased appetite/hunger/weight gain" ratings increased significantly as a function of dose, with differences between low and high doses (1.95 and 1.73, respectively, p = .01), but not by time nor any interaction. In the combined group of individuals with affective disorders and socioeconomically disadvantaged women, weight and "increased appetite/hunger/weight gain" ratings increased significantly by dose, with differences between low and high doses (1.43 vs. 0.73 kg, p = .003 and 2.00 vs. 1.76, p = .02, respectively). Among individuals with OUD, there were no significant effects of any kind on either outcome. Individuals with affective disorders and socioeconomically disadvantaged women gained weight and reported more subjective appetite/weight gain when given 0.4, but not 2.4 mg/g cigarettes, despite comparable decreases in nicotine exposure. However, neither change was clinically significant, suggesting minimal short-term adverse consequences of a nicotine reduction policy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A systematic review and meta-analysis of interventions to induce attempts to quit tobacco among adults not ready to quit.

The prevalence of past-year smoking cessation remains below 10% in the U.S. Most who smoke are not ready to quit in the near future. Cessation requires both (a) initiating a quit attempt (QA) and (b) maintaining abstinence. Most research has focused on abstinence among people already motivated to quit. We systematically reviewed interventions to promote QAs among people not motivated to quit tobacco. We searched PubMed, CENTRAL, PsycINFO, Embase, and our personal libraries for randomized trials of tobacco interventions that reported QAs as an outcome among adults not ready to quit. We screened studies and extracted data in duplicate. We pooled findings of the 25 included studies using Mantel-Haenszel random effects meta-analyses when ≥ 2 studies tested the same intervention. Most (24) trials addressed cigarettes and one addressed smokeless tobacco. Substantial heterogeneity among trials resulted in a series of small meta-analyses. Findings indicate varenicline may increase QAs more than no varenicline, n = 320; RR = 1.4, 95% CI [1.1, 1.7]; I² = 0%, and nicotine replacement therapy (NRT) may increase QAs more than no NRT, n = 2,568; RR = 1.1, 95% CI [1.02, 1.3]; I² = 0%. Pooled effects for motivational counseling, reduction counseling, and very low nicotine content cigarettes showed no clear evidence of benefit or harm. The evidence was judged to be of medium to very low certainty due to imprecision, inconsistency, and risk of bias, suggesting that further research is likely to change interpretation of our results. Findings demonstrate the need for more high-quality research on interventions to induce QAs among adults not ready to quit tobacco. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Practical guidance on modeling choices for the virtual twins method

ABSTRACT Individuals can vary drastically in their response to the same treatment, and this heterogeneity has driven the push for more personalized medicine. Accurate and interpretable methods to identify subgroups that respond to the treatment differently from the population average are necessary to achieving this goal. The Virtual Twins (VT) method is a highly cited and implemented method for subgroup identification because of its intuitive framework. However, since its initial publication, many researchers still rely heavily on the authors’ initial modeling suggestions without examining newer and more powerful alternatives. This leaves much of the potential of the method untapped. We comprehensively evaluate the performance of VT with different combinations of methods in each of its component steps, under a collection of linear and nonlinear problem settings. Our simulations show that the method choice for Step 1 of VT, in which dense models with high predictive performance are fit for the potential outcomes, is highly influential in the overall accuracy of the method, and Superlearner is a promising choice. We illustrate our findings by using VT to identify subgroups with heterogeneous treatment effects in a randomized, double-blind trial of very low nicotine content cigarettes.

Tobacco endgame and priority populations: a scoping review

AimTo summarise the research literature on the impacts or perceptions of policies to end tobacco use at a population level (ie, tobacco endgame policies) among people from eight priority population...

Impact of reduced nicotine content on behavioral economic measures of cigarette reinforcement in adolescents who smoke cigarettes

BackgroundPublic health officials in the U.S. and New Zealand are considering a reduced nicotine standard for cigarettes to reduce their addictive potential. This study’s aim was to evaluate the effects of nicotine reduction on the reinforcing efficacy of cigarettes in adolescents who smoke, which has implications for this policy’s potential for success. MethodsAdolescents who smoked cigarettes daily (n = 66; mean age: 18.6) participated in a randomized clinical trial assessing effects of assignment to very low nicotine content (VLNC; 0.4 mg/g nicotine) or normal nicotine content (NNC; 15.8 mg/g nicotine) cigarettes. Hypothetical cigarette purchase tasks were completed at baseline and the end of Week 3 and demand curves fit to the data. Linear regressions estimated effects of nicotine content on demand for study cigarettes at baseline and Week 3 and associations between baseline demand for cigarette consumption at Week 3. ResultsAn extra sum of squares F-test of fitted demand curves indicated that demand (α) was more elastic among VLNC participants at baseline and Week 3 (F(2, 1016)= 35.72, p < 0.001). Adjusted linear regressions indicated demand was more elastic (ß= 1.45, p < 0.01) and maximum expenditure (Omax) lower (ß= −1.42, p-0.03) among VLNC participants at Week 3. More elastic demand for study cigarettes at baseline predicted lower consumption of cigarettes at Week 3 (p’s < 0.01). ConclusionsA nicotine reduction policy may reduce the reinforcing value of combustible cigarettes among adolescents. Future work should investigate likely responses to such a policy among youth with other vulnerabilities and evaluate the potential for substitution to other nicotine containing products.

Subjective experiences, contexts, and risk perceptions of very low nicotine content cigarettes and electronic cigarettes among people with depression and anxiety disorders who smoke

BackgroundA low-nicotine product standard is currently under consideration by the U.S. Food and Drug Administration (FDA). This standard may be more effective if alternative, non-combusted sources of nicotine are concurrently available. This qualitative study explored the lived experiences of people with depression and anxiety disorders who used very low nicotine content (VLNC) cigarettes with or without e-cigarettes during a randomized controlled trial. MethodsWe conducted semi-structured qualitative interviews with participants (n = 20) as they completed a 16-week blinded trial of VLNC cigarettes with or without electronic cigarettes. Interviews explored 1) experiences with these products, 2) social and environmental contexts for use and 3) relative risk perceptions. Interviews were transcribed and analyzed using a hybrid inductive and deductive thematic analysis. ResultsConcurrent access to e-cigarettes helped to ease the transition from usual-brand cigarettes to VLNC cigarettes. Some participants held misperceptions that VLNC cigarettes could reduce cancer risk whereas others did not. Participants expressed skepticism about the safety of e-cigarettes and the authenticity of the VLNC cigarettes. Smoking restrictions influenced e-cigarette use in some instances, but product preference was the overriding factor that influenced use. Participants did not note effects on psychiatric symptoms. ConclusionsShould a nicotine reduction policy be implemented with e-cigarettes concurrently available on the market, tailored messaging for people with anxiety and depression disorders may be necessary to educate people about and the availability of alternative sources of nicotine, such as e-cigarettes, as well as the relative risk of VLNC cigarettes and e-cigarettes.

Disparities in Nicotine Addictiveness and Cancer Harm Perceptions Among U.S. Adults: A Trend Analysis Using the Health Information National Trends Survey.

Recent research has found widespread misperceptions about nicotine. This study tests perceptions among U.S. adults with respect to nicotine addictiveness and cancer harm, while distinguishing between nicotine misperceptions (ie an incorrect response) and "don't know" (DK) responses. Data from three cycles of the Health Information National Trends Survey, fielded in 2015, 2017, and 2019 were merged for analysis. Weighted multinominal logistic regression models were conducted where nicotine addictiveness and cancer harm beliefs (DK, incorrect, and correct responses) were regressed on survey year and demographic variables. We also tested for interactions between survey year and demographic variables to assess if previously identified disparities had evolved during these years. Analyses showed lower odds of misperceptions about nicotine addictiveness, but higher odds of misperceptions about nicotine cancer harm in 2019 compared to 2015. There was no change in DK responses during these years. Disparities by sociodemographics and tobacco use status were observed, mostly for cancer harm. Survey year significantly interacted with age in the model for cancer harm, which was driven primarily by increased incorrect responses and decreased DK responses over time among the youngest age group (18-34 years). There were no significant interactions between survey year and race and ethnicity or level of educational attainment. Disparities in nicotine addictiveness and cancer harm perceptions reflect the uneven distribution of knowledge in the U.S. adult population. Nicotine cancer harm misperceptions are increasing and educational efforts to address this misperception are warranted. Future educational efforts targeting nicotine addictiveness beliefs may benefit by focusing on DK responders. The growing trend of misperceptions of nicotine's role in cancer harm may negatively impact perceptions about nicotine replacement therapy and low nicotine content cigarettes. Future efforts should focus on correcting nicotine cancer harm misperception, particularly among young adults.

Immediate Switching to Reduced Nicotine Cigarettes in a U.S.-Based Sample: The Impact on Cannabis Use and Related Variables at 20 Weeks.

The FDA proposed rule-making to reduce nicotine in cigarettes to minimally addictive levels. Research suggests decreasing nicotine levels (i.e. very low nicotine content cigarettes [VLNCs]) produced greater quit attempts, reduced smoking, and reduced exposure to harmful constituents among smokers. The impact of long-term VLNC use among people who co-use cigarettes and cannabis on non-tobacco-specific toxicant and carcinogen exposure has not been investigated. This study presents secondary analyses of a controlled clinical trial examining switching to VLNC (versus a normal nicotine cigarettes control group [NNCs]) between people who co-use cigarettes and cannabis (n = 174) versus smoked cigarettes (n = 555). Linear mixed-effects models compared changes in smoking behavior, and tobacco-specific (i.e. total nicotine equivalents [TNE], 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone [NNK; total NNAL]) and non-tobacco-specific (i.e. carbon monoxide (CO), 2-cyanoethylmercapturic acid [CEMA], phenanthrene tetraol [PheT]) toxicant and carcinogen exposure at week 20 (with random intercept for participants). Cannabis use was measured among co-use groups. CO was significantly lower only among the cigarette-only group assigned VLNCs (interaction: p = .015). Although both VLNC groups demonstrated decreased CEMA, greater decreases emerged among the cigarette-only group (interaction: p = .016). No significant interactions emerged for TNE, cigarettes per day (CPD), NNAL, and PheT (ps > .05); both VLNC groups decreased in TNE, CPD, and NNAL. Only the cigarette-only group assigned VLNCs demonstrated decreased PheT (p < .001). The VLNC co-use group showed increased cannabis use over time (p = .012; 0.5 more days per week by week 20). Those who co-use cannabis and cigarettes may still be at risk for greater exposure to non-tobacco-specific toxicants and carcinogens compared to those who only smoke cigarettes. The present study is the longest longitudinal, prospective comparison study of smoking behavior and exposure to harmful constituents among those who co-use cigarettes and cannabis versus cigarette-only after immediately switching to very low nicotine content cigarettes (VLNC). Those who co-use experienced similar reductions in CPD and tobacco-specific exposure, compared to those who only use cigarettes. However, co-use groups experienced smaller reductions in non-tobacco-specific toxicants and carcinogens compared to the cigarette-only group, potentially because of combustible cannabis use. Additionally, those who co-use and switched to VLNC may be susceptible to slight increases in cannabis use (approximately two more days per year).

Monoamine oxidase inhibition in cigarette smokers: From preclinical studies to tobacco product regulation.

Monoamine oxidase (MAO) activity is reduced in cigarette smokers and this may promote the reinforcing actions of nicotine, thereby enhancing the addictive properties of cigarettes. At present, it is unclear how cigarette smoking leads to MAO inhibition, but preclinical studies in rodents show that MAO inhibition increases nicotine self-administration, especially at low doses of nicotine. This effect of MAO inhibition develops slowly, likely due to plasticity of brain monoamine systems; studies relying on acute MAO inhibition are unlikely to replicate what happens with smoking. Given that MAO inhibition may reduce the threshold level at which nicotine becomes reinforcing, it is important to consider this in the context of very low nicotine content (VLNC) cigarettes and potential tobacco product regulation. It is also important to consider how this interaction between MAO inhibition and the reinforcing actions of nicotine may be modified in populations that are particularly vulnerable to nicotine dependence. In the context of these issues, we show that the MAO-inhibiting action of cigarette smoke extract (CSE) is similar in VLNC cigarettes and cigarettes with a standard nicotine content. In addition, we present evidence that in a rodent model of schizophrenia the effect of MAO inhibition to enhance nicotine self-administration is absent, and speculate how this may relate to brain serotonin systems. These issues are relevant to the MAO-inhibiting effect of cigarette smoking and its implications to tobacco product regulation.

Menthol preference moderates the relationship between cigarette nicotine content choice and reactions in young adults who smoke infrequently

BackgroundHalf of young adults who smoke use menthol cigarettes, which is associated with continued smoking and greater nicotine dependence. Additionally, early subjective reactions to cigarettes predict future use. Menthol may blunt the sensory effects of nicotine. We investigated the moderating role of menthol on subjective reactions to, and choice of varied nicotine content cigarettes in young adults who smoke infrequently. MethodsIn three counterbalanced, double-blinded sessions, young adults who smoke ≤ 15 days/month smoked fixed doses from very low (VLNC), intermediate (INC), and normal (NNC) nicotine content cigarettes, which were menthol or non-menthol depending on preference. Participants chose their preferred cigarette in a final session. Positive and negative subjective reactions were measured in each session. ANOVA tests investigated the relationship between menthol preference, nicotine content, and subjective reactions. ResultsParticipants (N = 87) were 18–25 years old and reported smoking 15.2 cigarettes per month over 8 days (35 % menthol). Non-menthol preferring participants had increased negative reactions with greater nicotine content (F(1, 55)= 10.76, p < .001); menthol preferring participants did not. Choice of higher nicotine cigarettes was associated with having reported a greater difference in positive reactions to NNC and VLNC for non-menthol preferring participants (F(1, 55)= 12.72, p < .001) but not for menthol preferring participants. ConclusionsYoung adults who smoke infrequently are a priority tobacco control population given their high risk of transitioning to daily smoking. Results from this study in the form of subjective reactions indicate that a menthol ban is required for a nicotine reduction standard to be maximally effective in this vulnerable group.

Reducing Misperceptions About Very Low Nicotine Content Cigarettes: Insights From Adults Who Smoke.

Many people incorrectly think that very low nicotine content (VLNC) cigarettes are less carcinogenic than current cigarettes. This risk misperception by people who smoke could reduce motivation to quit under a nicotine reduction policy. We qualitatively examined perspectives on campaign messages designed to reduce misperceptions. Adults who smoke from North Carolina participated in online interviews. After being introduced to the idea of a VLNC policy, participants were shown VLNC messages and asked about their perceptions on the clarity, understandability, persuasiveness, and meaning of the messages. We conducted a thematic content analysis of the transcripts. Thirty adults who smoke cigarettes participated (15 females, 13 males, 2 nonbinary) with a mean age of 43 years. Central themes that emerged were: (1) Confusion about the proposed VLNC cigarette policy affected how messages were interpreted; (2) Messages that promote self-efficacy for quitting rather than guilt or fear were better received; and (3) Direct and succinct messages were seen as more able to grab attention and inform people who smoke. Some participant concerns focused on whether VLNC cigarettes would relieve their nicotine cravings and whether they would need to smoke more VLNC cigarettes to feel satisfied. Campaign messages to educate the public about the harmful effects of smoking VLNC cigarettes may be more effective if people who smoke are informed about the policy's rationale to understand why nicotine is removed rather than the other harmful chemicals. Messages should also acknowledge the difficulty of quitting and be short and direct to capture attention. Adults who smoke have some confusion about nicotine reduction in cigarettes and this affects how they perceive potential communication campaign messages about the risk of smoking VLNC cigarettes. In our qualitative research, we found that adults who smoke prefer messages about VLNC cigarettes that acknowledge the challenge of quitting and that are direct and succinct. With further development, campaign messages may be able to reduce misperceptions about VLNC cigarettes and maximize the public health benefit of a nicotine reduction policy.

Predictors of Adherence Among Vulnerable Populations of Adults Assigned to Smoke Very Low Nicotine Content Cigarettes.

Regulators are considering reducing the nicotine content in cigarettes to a minimally addictive level. This could particularly benefit smokers from populations vulnerable to heavy smoking and difficulties quitting. We assessed predictors of adherence among adults from vulnerable populations assigned to use very low nicotine content cigarettes (VLNCs) in randomized clinical trials, to identify characteristics of those who require additional assistance if a nicotine reduction policy were implemented. Data came from three populations of vulnerable adult smokers assigned to use VLNC cigarettes (0.4 mg/g nicotine) during 12-week randomized controlled trials (n = 286): Socioeconomically disadvantaged women of reproductive age, opioid-maintained adults, and adults with affective disorders. Logistic and linear regressions modeled predictors of adherence based on changes in cotinine at week-6 and week-12 assessments relative to baseline, and as a 90% reduction in cotinine relative to baseline (full adherence: yes/no). Predictors included satisfaction with study cigarettes, craving, nicotine dependence severity, withdrawal, population membership, baseline affective-disorder symptoms, and sociodemographic characteristics. Dependence severity was negatively associated with both adherence measures at week 6 (p < .01), whereas increased satisfaction with study cigarettes and age were positively associated with both measures at weeks 6 and 12 (p < .01). Opioid-maintained adults exhibited reduced adherence and were less likely to reach full adherence at week 12 compared to disadvantaged women (p = .02). Factors associated with VLNC adherence in vulnerable populations are similar to those in the general population of smokers. Furthermore, studies are indicated investigating nicotine supplements (e.g., e-cigarettes, NRT) to support highly dependent adults faced with using VLNCs. This study identified factors predicting difficulty maintaining adherence to a regimen of very low nicotine content cigarettes (VLNC) among adults from vulnerable populations. Findings suggested that factors predicting difficulty maintaining adherence (greater nicotine dependence and low satisfaction with study-provided VLNC) were common across vulnerable smokers and the general population of adults who smoke. Furthermore, research should investigate alternatives to support highly dependent adults, such as pairing VLNC with supplemental, noncombusted nicotine. Some vulnerable populations (e.g., opioid-maintained adults) may be especially in need of supplemental, noncombusted nicotine.

Effects of very low nicotine content cigarettes on smoking across vulnerable populations

There has been long-standing interest in a reduced-nicotine product standard for combusted tobacco, which is within the regulatory purview of the Food and Drug Administration (FDA). In weighing whether to establish this standard, it is important to consider potential responses among people who are at elevated risk for tobacco-related health harms. In this narrative review, we summarize studies of very low nicotine content (VLNC) cigarettes conducted between 2010 and 2021 in groups that the FDA has identified as vulnerable populations. Studies conducted to date in adults with mental health conditions, adults with opioid use disorder, socioeconomically-disadvantaged adults, and youth or young adults indicate that immediate switching to VLNC cigarettes decreases smoking, with minimal or no unintended negative consequences. Few studies have investigated the effects of VLNC cigarettes in racial or ethnic minorities, people who smoke menthol cigarettes, and pregnant women, but initial findings suggest that responses of these individuals are similar to responses observed in other vulnerable populations. We are not aware of studies that have investigated VLNC cigarettes in military/veteran populations, sexual or gender minority individuals, or people living in underserved rural environments. Future research directions include understanding how to promote cessation in the context of a reduced-nicotine standard, and how to correct VLNC misperceptions in vulnerable populations. Nevertheless, the evidence to date indicates that a reduced-nicotine standard is likely to have the same beneficial effects on smoking reductions as it does in less vulnerable populations, which should provide some confidence in pursuing this regulatory approach.

Effects of Very Low Nicotine Content Cigarette use on Cigarette Reinforcement among Smokers with Serious Mental Illness

BackgroundAmong people without psychiatric disorders who smoke, very low nicotine content (VLNC) cigarette use reduces cigarette reinforcement. Whether this is true of people with serious mental illness (SMI) who smoke is unknown. Using a hypothetical purchase task, we compared the effects of 6-week use of VLNC versus normal nicotine content (NNC) cigarettes on study cigarette and usual brand (UB) cigarette reinforcement among people with SMI who smoke. MethodsAfter a baseline period of UB cigarette use, participants with SMI (n = 58) were randomized to use NNC cigarettes (15.8 mg nicotine/g tobacco) or VLNC cigarettes (0.4 mg/g) for 6 weeks. At Week 6, they completed the CPT for both their assigned study cigarette and UB. The groups were compared on demand intensity (number of cigarettes purchased at no cost) and elasticity (rate of decline in demand as price increases) using extra sum-of-squares F-tests. The effects of treatment on demand indices while controlling for covariates were assessed using hierarchical regression. ResultsAt Week 6, intensity of demand for study cigarettes was lower and elasticity was higher for the VLNC group relative to the NNC group (p < 0.0001). Furthermore, intensity of demand for UB cigarettes was lower for participants in the VLNC group relative to participants in the NNC group (p < 0.01). When controlling for baseline cigarettes per day, intensity remained significantly different for study cigarettes and usual brand cigarettes at Week 6. ConclusionA nicotine reduction policy may reduce cigarette reinforcement in this vulnerable population.

The Impact of the Covid-19 Pandemic on Smoking Among Vulnerable Populations.

AimWhile accumulating evidence suggests that people modified their smoking during the ongoing COVID-19 pandemic, it remains unclear whether those most at risk for tobacco-related health disparities did so. The current study examined changes in smoking among several vulnerable smoker populations during the COVID-19 pandemic.MethodsA web-based survey was distributed in 2020 to 709 adults with socioeconomic disadvantage, affective disorders, or opioid use disorder who participated in a previous study investigating the effects of very low nicotine content (VLNC) cigarettes on smoking. Current smoking status and rate, and adoption of protective health behaviors in response to the pandemic (e.g., social distancing, mask wearing) were examined.ResultsAmong 332 survey respondents (46.8% response rate), 84.6% were current smokers. Repeated measures ANOVA showed that current cigarettes/day (CPD) was higher during COVID than pre-COVID (12.9±1.0 vs 11.6±1.0; p<.001). Most respondents had adopted protective health behaviors to prevent infection (>79% for all behaviors). More than half indicated that they were still leaving their homes specifically to buy cigarettes (64.6%) and were buying more packs per visit to the store (54.5%) than pre-COVID. Individuals unemployed at the time of the survey experienced greater increases in CPD (from 11.4±1.4 to 13.3±1.4, p=.024) as did those with higher levels of anxiety (from 11.5±1.1 to 13.6±1.1, p<.001).ConclusionsSmoking increased during the COVID-19 pandemic in this sample of adults from vulnerable populations, even while most adopted protective health measures to prevent infection. Unemployment and anxiety might identify those at greatest risk for increases in tobacco use.ImplicationsIndividuals from populations especially vulnerable to smoking might be at risk for greater harm from cigarette smoking during times of pandemic-related stress. Public health interventions are warranted to ameliorate increases in smoking among these populations. Special attention should be paid to those experiencing unemployment and high anxiety.

A permutation procedure to detect heterogeneous treatment effects in randomized clinical trials while controlling the type I error rate.

Secondary analyses of randomized clinical trials often seek to identify subgroups with differential treatment effects. These discoveries can help guide individual treatment decisions based on patient characteristics and identify populations for which additional treatments are needed. Traditional analyses require researchers to pre-specify potential subgroups to reduce the risk of reporting spurious results. There is a need for methods that can detect such subgroups without a priori specification while allowing researchers to control the probability of falsely detecting heterogeneous subgroups when treatment effects are uniform across the study population. We propose a permutation procedure for tuning parameter selection that allows for type I error control when testing for heterogeneous treatment effects framed within the Virtual Twins procedure for subgroup identification. We verify that the type I error rate can be controlled at the nominal rate and investigate the power for detecting heterogeneous effects when present through extensive simulation studies. We apply our method to a secondary analysis of data from a randomized trial of very low nicotine content cigarettes. In the absence of type I error control, the observed type I error rate for Virtual Twins was between 99% and 100%. In contrast, models tuned via the proposed permutation were able to control the type I error rate and detect heterogeneous effects when present. An application of our approach to a recently completed trial of very low nicotine content cigarettes identified several variables with potentially heterogeneous treatment effects. The proposed permutation procedure allows researchers to engage in secondary analyses of clinical trials for treatment effect heterogeneity while maintaining the type I error rate without pre-specifying subgroups.

Early Changes in Puffing Intensity When Exclusively Using Open-Label Very Low Nicotine Content Cigarettes.

In response to reducing cigarette nicotine content, people who smoke could attempt to compensate by using more cigarettes or by puffing on individual cigarettes with greater intensity. Such behaviors may be especially likely under conditions where normal nicotine content (NNC) cigarettes are not readily accessible. The current within-subject, residential study investigated whether puffing intensity increased with very low nicotine content (VLNC) cigarette use, relative to NNC cigarette use, when no other nicotine products were available. Sixteen adults who smoke daily completed two four-night hotel stays in Charleston, South Carolina (United States) in 2018 during which only NNC or only VLNC cigarettes were accessible. We collected the filters from all smoked cigarettes and measured the deposited solanesol to estimate mouth-level nicotine delivery per cigarette. These estimates were averaged within and across participants, per each 24-h period. We then compared the ratio of participant-smoked VLNC and NNC cigarette mouth-level nicotine with the ratio yielded by cigarette smoking machines (when puffing intensity is constant). Average mouth-level nicotine estimates from cigarettes smoked during the hotel stays indicate participants puffed VLNC cigarettes with greater intensity than NNC cigarettes in each respective 24-h period. However, this effect diminished over time (p &lt; .001). Specifically, VLNC puffing intensity was 40.0% (95% CI: 29.9, 53.0) greater than NNC puffing intensity in the first period, and 16.1% (95% CI: 6.9, 26.0) greater in the fourth period. Average puffing intensity per cigarette was elevated with exclusive VLNC cigarette use, but the extent of this effect declined across four days. In an environment where no other sources of nicotine are available, people who smoke daily may initially attempt to compensate for cigarette nicotine reduction by puffing on individual cigarettes with greater intensity. Ultimately, the compensatory behavior changes required to achieve usual nicotine intake from VLNC cigarettes are drastic and unrealistic. Accordingly, people are unlikely to sustain attempts to compensate for very low cigarette nicotine content.

Perceptions of Nicotine Reduction Policy in the United States: A Qualitative Study.

Several countries are considering a reduced nicotine policy that would make cigarettes minimally or nonaddictive. This qualitative study documents reactions to the policy that should be addressed by future communication efforts. In 2020, we recruited participants in Atlanta, GA and San Francisco, CA (27 people who exclusively smoke, 25 who dual use cigarettes and e-cigarettes, 32 who formerly smoked, and 31 young adults who do not smoke). We held 16 focus groups: 2 focus groups for each smoking status in each city. Participants viewed messages about very low nicotine content cigarettes (VLNCs) and were asked about their reactions to each message and their overall response to the reduced nicotine policy. While responses to the policy were predominantly positive, focus group discussion also revealed concerns, questions, and misunderstandings (referred to here collectively as "perceptions") that may need to be addressed if a reduced nicotine policy is enacted. Participants expressed perceptions related to the policy intent, including that the FDA has ulterior motives, adoption/ implementation, including that nicotine would have to be replaced with other chemicals if removed or that the policy would be unfeasible to implement, and effectiveness, including concern that VLNCs would still be addictive or the policy would backfire. Addressing perceptions about reduced nicotine policy intent, adoption/implementation, and effectiveness could be key in creating public support and political motivation to move forward with such a policy. Countries contemplating adopting such a policy should consider pairing it with communications that address these perceptions. This study is one of very few to use qualitative methods to explore potentially problematic perceptions about nicotine reduction policy among US adults. Results illuminated new policy-specific concerns, questions, and misunderstandings about the reduced nicotine policy intent, adoption/implementation, and effectiveness. Identifying, studying, and addressing relevant perceptions may play a key role in generating support in countries contemplating such a policy.