Reduced Nicotine Cigarettes and E-Cigarettes in High-Risk Populations: 3 Randomized Clinical Trials.

Importance: Prohibiting the sale of commonly preferred e-cigarette flavors (eg, fruity and sweet) to discourage use among youths poses a risk of diminishing efforts to decrease smoking in adults. Objective: To compare reductions in smoking achieved in adults with psychiatric conditions or lower educational level using very low nicotine content (VLNC) cigarettes alone, combined with e-cigarettes limited to tobacco flavor (TF), or combined with e-cigarettes in participant-preferred flavors. Design, Setting, and Participants: Three randomized clinical trials were conducted for 16 weeks from October 2020 through November 2023 at the University of Vermont, Brown University, and Johns Hopkins University. Participants were adults who smoked daily and were not planning to quit in the next 30 days. These participants were from 3 at-risk populations: those with affective disorders, exemplifying mental illness; those with opioid use disorder, exemplifying substance use disorders; and females of reproductive age with a high-school education or less, exemplifying lower educational level. Participants were randomly assigned to 1 of 4 experimental conditions: (1) normal nicotine content (NNC) cigarettes only; (2) VLNC cigarettes only; (3) VLNC cigarettes plus e-cigarettes with classic TF (hereafter, VLNC + TF); and (4) VLNC cigarettes plus e-cigarettes with preferred flavors (hereafter, VLNC + PF). Interventions: The NNC cigarettes contained 15.8 mg nicotine/g tobacco, the VLNC cigarettes contained 0.4 mg nicotine/g tobacco, the VLNC + TF had pods containing 5% nicotine by weight and only classic TF, and the VLNC + PF had pods containing 5% nicotine in 8 flavors (including fruity and sweet) from which participants selected 3 flavors. Main Outcomes and Measures: The primary outcome was mean total cigarettes smoked per day (CPD) during week 16. Tobacco-related biomarkers were assessed, including total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific carcinogen. Results: A total of 326 participants (mean [SD] age, 40.09 [10.79] years; 243 females [74.5%]) from 3 randomized clinical trials were included. The VLNC cigarettes decreased total CPD, with least square (LS) means (SEMs) of 22.54 (1.59) in the NNC, 14.32 (1.32) in the VLNC, 11.76 (1.18) in the VLNC + TF, and 7.63 (0.90) in the VLNC + PF conditions. Each VLNC condition differed significantly from NNC, with an adjusted mean difference (AMD) of -8.21 (95% CI, -12.27 to -4.16; P < .001) in the VLNC, -10.78 (95% CI, -14.67 to -6.90; P < .001) in the VLNC + TF, and -14.91 (95% CI, -18.49 to -11.33; P < .001) in the VLNC + PF conditions. Participants in the VLNC + PF condition also decreased smoking below the VLNC and the VLNC + TF conditions (AMDs, -6.70 [95% CI, -9.84 to -3.55; P < .001] and -4.13 [95% CI, -7.05 to -1.21; P = .02]); the VLNC and VLNC + TF conditions did not differ significantly. Consistent with decreases in CPD, NNAL levels in the VLNC + PF condition were lower than in all other conditions, with AMDs (in pmol/mg creatinine) of -0.94 (95% CI, -1.41 to -0.47; P < .001) compared with the NNC condition, -0.47 (95% CI, -0.87 to -0.08; P = .03) compared with the VLNC condition, and -0.46 (95% CI, -0.83 to -0.10; P = .04) compared with the VLNC + TF condition. Conclusions and Relevance: These results provide further evidence that a reduced-nicotine standard for cigarettes has the potential to decrease smoking and tobacco-toxicant exposure in high-risk populations and that these effects may be enhanced when adults can access e-cigarettes in commonly preferred flavors. Trial Registration: ClinicalTrials.gov Identifiers: NCT04092387, NCT04090879, NCT04092101.

Racial/ethnic differences in the acute effects of reduced nicotine content cigarettes among adolescents who smoke.

OBJECTIVE: Reducing the nicotine content in cigarettes decreases their addictiveness and abuse liability, including among adolescents. Whether these effects differ by race/ethnicity is unknown. This study is a secondary analysis of previously published data collected between 2014-2017. We examined racial/ethnic differences in the effects of smoking cigarettes with varying nicotine content levels on subjective effects and tobacco withdrawal among adolescents who smoke daily. METHODS: Across two counterbalanced sessions, 50 adolescents recruited from Rhode Island (ages 15-19; 30 % Underrepresented Minorities [URM], 20 % Asians and Pacific Islanders [API]; 50 % Non-Hispanic Whites) self-administered a very low nicotine content (VLNC; 0.4 mg nicotine/g of tobacco) or normal nicotine content control (NNC; 15.8 mg/g) research cigarette following overnight abstinence. Subjective effects were reported post-administration and tobacco withdrawal outcomes were calculated from pre- to post-administration scores. Multilevel linear models tested main and interactive effects between cigarette nicotine content and race/ethnicity on all study outcomes. RESULTS: Participants reported lower positive subjective effects and reductions in smoking urges after smoking a VLNC cigarette relative to smoking an NNC cigarette (ps < 0.01). A main effect of race/ethnicity emerged, such that API (vs. URM and White) adolescents reported lower positive subjective effects, greater craving reduction, and higher cigarette aversion after smoking, regardless of nicotine content (ps < 0.05). Significant interactions were found between race/ethnicity and nicotine content for cigarette aversion, such that API adolescents rated VLNC (vs. NNC) cigarettes as less aversive than White and URM adolescents did (p = 0.03). CONCLUSIONS: Findings provide evidence that VLNC cigarettes may reduce abuse liability and tobacco withdrawal symptoms for adolescents across racial/ethnic groups and particularly for API youth.

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

INTRODUCTION: 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. METHODS: 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; 0.4 mg nicotine/g of tobacco) or Normal Nicotine Content (NNC; 15.8 mg/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. RESULTS: 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. CONCLUSIONS: 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. IMPLICATIONS: 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.

Reduced nicotine in cigarettes in a marketplace with alternative nicotine systems: randomized clinical trial.

Background: Reducing cigarette addictiveness has the potential to avert millions of yearly tobacco-related deaths worldwide. Substantially reducing nicotine in cigarettes decreases cigarette consumption, but no large clinical trial has determined the effects of reduced-nicotine cigarettes when other nicotine-containing products are available. The aim of this study was to examine the effects of reduced-nicotine cigarettes in the context of the availability of alternative nicotine delivery systems. Methods: In a U.S. six-site, open-label, parallel-arm study, smokers were randomized for twelve weeks to an experimental marketplace containing cigarettes with either 0.4 mg or 15.8 mg nicotine per gram of tobacco; all had access to non-combusted alternative nicotine delivery systems (e.g., e-cigarettes; medicinal nicotine). Group differences in the primary outcomes (cigarettes per day, number of smoke-free days) were examined using linear and negative binomial regression, respectively (Trial Registration: NCT03272685). Findings: Among 438 randomized participants (mean [standard deviation (SD), range] age, 44.5 [11.9, 20-73] years, 225 [51.4%] women, 282 [64.4%] White and 339 [77.4%] trial completers), those in the 0.4 mg vs. 15.8 mg nicotine cigarette condition experienced significantly lower cigarettes per day at the end of intervention (mean [SD], 7.05 [7.88] vs. 12.95 [9.07], adjusted mean difference, -6.21 [95% CI, -7.66 to -4.75], P < 0.0001) and greater smoke-free days during intervention (mean [SD], 18.59 [27.97] vs. 5.06 [13.77], adjusted rate ratio, 4.25 [95% CI, 2.58-6.98], P < 0.0001). Interpretation: A reduced-nicotine cigarette standard in the context of access to other non-combusted nicotine products has the potential to benefit public health. Funding: U.S. NIH/FDA U54DA03165.

Reactions to a Nicotine Reduction Policy Among Adolescents Who Smoke: A Qualitative Study.

INTRODUCTION: The Biden administration is pursuing a nicotine reduction policy in the U.S. to render cigarettes less addictive. In this study, we qualitatively investigated adolescents' subjective responses to very low nicotine content (VLNC) cigarettes, reasons for incomplete adherence to using them, and their expected responses to a nicotine reduction policy. METHODS: Adolescents who smoke cigarettes daily (ages 15-19; N=60) were enrolled in a three-week double-blind randomized clinical trial and assigned to smoke either normal nicotine content (NNC) or VLNC research cigarettes. Following the trial, 52 participants completed qualitative interviews about their reactions to the cigarettes and to the idea of a nicotine reduction policy. We utilized a template style approach to thematic analysis involving immersion in the data, codebook development with both inductive and deductive codes, and iterative refinement of themes. RESULTS: Reasons for incomplete adherence to smoking only research cigarettes focused on dislike for cigarette taste and lower satisfaction compared to usual brand cigarettes. Negative evaluations of research cigarettes were common across both groups. Many participants in both groups reported that they would decrease their smoking or quit entirely if the research cigarettes were the only ones legally available for purchase in the U.S. CONCLUSIONS: Adolescents may respond to a cigarette nicotine reduction policy by decreasing their cigarette smoking and eventually quitting. These findings suggest a need for public health strategies to reduce smoking initiation and progression in young people and to encourage cessation in the context of a nicotine reduction policy. IMPLICATIONS: Participants' negative subjective responses and challenges with research cigarette adherence offer insight into factors that might influence young people's reactions to a real-world nicotine reduction policy. Adolescents who smoke may increase their use of alternative tobacco products, especially e-cigarettes, if this policy were implemented. Specifically, themes identified across participant responses highlight important considerations for how such a policy might be implemented with specific attention to the unique smoking behaviors and needs of this vulnerable population.

Cigarette smoking and cognitive task performance: Experimental effects of very-low nicotine-content cigarettes.

Reductions in the nicotine content of cigarettes decrease smoking rate and dependence severity, but effects on cognition are less well established. The potential impacts of very-low nicotine-content (VLNC) cigarettes on cognitive task performance must be evaluated, especially in vulnerable populations. The aim of the present study is to experimentally examine the effects of VLNC cigarettes on cognitive performance. Adults who smoked daily (n = 775) from three vulnerable populations (socioeconomically disadvantaged reproductive-age women, individuals with opioid use disorder, affective disorders) were examined. Participants were randomly assigned to normal nicotine content (NNC; 15.8 mg nicotine/g tobacco) or VLNC (2.4 mg/g or 0.4 mg/g) cigarettes for 12 weeks. Response inhibition (stop-signal task), working memory (n-back task; n of 2-n of 0), and cognitive interference (nicotine Stroop task) were assessed at baseline, 2, 6, and 12 weeks. Results were analyzed using mixed-model repeated-measures analyses of variance. Extended exposure to VLNC cigarettes produced no significant changes in any measure of cognitive performance compared to NNC cigarettes. Over weeks, response times on the n-back task decreased across doses. No significant effects were observed on the stop-signal or nicotine Stroop tasks. All three vulnerable populations performed comparably on all three cognitive tasks. Extended exposure to VLNC cigarettes produced no impairments in cognitive performance on any of the assessed tasks compared to NNC cigarettes. These findings are consistent with the larger literature detailing other consequences following exposure to VLNC cigarettes and are encouraging for the adoption of a nicotine-reduction policy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Examining the predictive utility of behavioral economic demand indices and subjective effects on the actualized reinforcing value of menthol cigarettes and potential alternatives.

INTRODUCTION: Considering recent and proposed bans on menthol cigarettes, methods are needed to understand the substitutability of potential menthol cigarette alternatives (MCAs) for menthol cigarettes. This study examined the prospective relationship between behavioral economic demand indices and subjective effects of usual brand menthol cigarettes (UBMC) and preferred MCAs with subsequent performance on a laboratory-based concurrent-choice task comparing UBMC and MCAs. METHODS: Eighty participants who typically smoked menthol cigarettes completed this clinical lab study. After sampling each product, participants completed the cigarette purchase task (CPT) and modified cigarette evaluation questionnaire (mCEQ). Following one-week of substituting their preferred MCA for their UBMC, participants completed a 90-min concurrent-choice self-administration task comparing their UBMC and preferred MCA. Linear regression models explored associations between CPT demand indices and mCEQ subjective effects in the lab with subsequent response effort for UBMCs on the concurrent-choice task. RESULTS: Three demand indices for UBMC were positively associated with UBMC response effort: Essential Value (EV; p=.02), Omax (p=.02), and breakpoint (p=.04). Four CPT demand indices for the preferred MCA significantly corresponded with UBMC response effort: EV (p=.03), Pmax (p=.04), Omax (p=.03), and breakpoint (p=.03). Subjective effects captured by the mCEQ were not associated with response effort. CONCLUSIONS: Demand indices reflecting Persistence (i.e., sensitivity to escalating price) predicted effort to obtain UBMC puffs on the concurrent-choice task. Among this sample, the CPT captured information on the relative reinforcing value (i.e., addiction potential) of combustible tobacco products similar to the longer self-administration task. IMPLICATIONS: In an ever-changing product market, assessing the reinforcing efficacy of menthol cigarettes and putative substitutes quickly and with validity is an important methodological tool for understanding abuse liability. Results suggest that behavioral economic demand indices of cigarette purchase task efficiently capture information on the relative reinforcing value of usual brand menthol cigarettes and plausible alternative tobacco products, similar to a 90-min in-laboratory self-administration task.

Examining Demand and Substitutability of Usual Brand Little Cigars/Cigarillos and Cigarettes in Young Adults Who Dual Use.

INTRODUCTION: Cigarette and little cigar/cigarillo (LCC) dual use is popular among young people and poses a substantial health risk. What remains unclear is the abuse liability of LCCs vs. cigarettes, LCCs' substitutability for cigarettes, and the influence of flavors on the abuse liability and substitutability of LCCs. METHODS: Sixty-five young adults (18-34 years) who dual use completed hypothetical purchase tasks to measure consumption of usual brand cigarettes and LCCs in 24 hours at increasing prices (demand), and LCC consumption at increasing cigarette prices (substitution). Three demand indices were calculated from raw data: breakpoint (price after which consumption reaches 0), Omax (maximum daily expenditure), and Pmax (price at maximum expenditure). Two indices were estimated using nonlinear mixed-effects modeling: intensity (consumption when free) and price-sensitivity (rate of decline in consumption as price increases). Substitution, and associations of flavored use with demand and substitution, were estimated using linear mixed models. RESULTS: Results indicated similar abuse liability for LCCs and cigarettes. Intensity was greater for cigarettes, but price-sensitivity was similar. Flavored LCC use was associated with lower price-sensitivity and greater intensity than unflavored. LCCs were significant substitutes for cigarettes, but the effect was small. Flavored use was not associated with substitution. CONCLUSIONS: Among young adults who dual use, LCCs and cigarettes had similar abuse liability, and those who used flavored had higher demand for their LCCs. A flavored cigar ban, as well as targeted prevention and cessation services for those who smoke flavored LCCs, may be important for reducing dual use in young adults. IMPLICATIONS: Cigarette and LCC dual use remains high among young adults. Using hypothetical purchase tasks with young adults who dual use, LCCs had abuse liability similar to cigarettes, but were only modest substitutes for cigarettes. Participants who used flavored LCCs reported greater abuse liability than those who used unflavored, but not greater substitution for cigarettes. Prevention and cessation services are needed to target LCCs in young people, particularly those smoking flavored products. A flavored cigar ban may help to reduce their demand.

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).

Substitutability of menthol cigarette alternatives: a clinical trial.

INTRODUCTION: This study assessed the substitutability of plausible combustible menthol cigarette alternatives (MCAs) for usual brand menthol cigarettes (UBMCs) in adults who smoke menthol cigarettes. METHODS: Following three in-lab sampling sessions, 80 adults aged 21-50 who smoke menthol cigarettes chose their preferred MCA: (1) a menthol roll-your-own cigarette (mRYO), (2) a menthol filtered little cigar (mFLC) or (3) a non-menthol cigarette (NMC). Participants were instructed to completely substitute their preferred MCA for their UBMC for 1 week and complete daily diaries documenting adherence and subjective effects. At the final lab visit, participants completed concurrent choice and cross-price elasticity tasks with their substitute product and UBMC as the comparator. RESULTS: Most (65%) participants chose mRYO as their preferred product, followed by NMC and mFLC. Adherence to MCA was high for all products across the week (range: 63%-88%). Positive subjective effects for mRYO decreased over time but remained numerically higher than the other MCA products; craving reduction also decreased for NMC across phases. In the progressive ratio task, participants chose their UBMC in 61.7% of choices; this did not differ by preferred MCA, although the median breakpoint was highest for mRYO and similar for mFLC and NMC. Cross-price elasticity comparing UBMC and the preferred product indicated high substitutability of each MCA at phase 3 (I values -0.70 to -0.82). CONCLUSIONS AND RELEVANCE: mRYOs were the most preferred MCA among the study products, but all MCAs were acceptable substitutes for UBMC using behavioural and economic measures in a short-term trial period.Trial registration number NCT04844762.

Acute effects of exercise among individuals with schizophrenia who smoke cigarettes.

People with schizophrenia (SCZ) have a shorter life expectancy than those without psychiatric conditions. Of note, people with SCZ have high rates of cigarette smoking, physical inactivity, and obesity. These factors all coalesce to contribute to compromised health in this population, with smoking as a primary contributor. Therefore, it is paramount to develop effective smoking cessation strategies for this population. The purpose of this study was to investigate whether walking at a brisk pace, relative to engaging in passive activity, would reduce acute cigarette craving, nicotine withdrawal, and negative affect (NA) among people with SCZ who smoke cigarettes. Using a within-subjects design, twenty participants completed four laboratory sessions with condition sequence counterbalanced: 1) exposure to smoking cues + treadmill walking, 2) exposure to neutral cues + treadmill walking, 3) exposure to smoking cues + passive/sedentary activity, 4) exposure to neutral cues + passive/sedentary activity. Relative to sedentary activity, walking resulted in greater decreases in nicotine withdrawal but did not significantly affect craving or NA. These results did not vary as a function of cue type. These findings suggest that walking may be a helpful strategy to reduce acute nicotine withdrawal symptoms among people with SCZ. However, it should be used in conjunction with other strategies for smoking cessation.

Reactions to using other nicotine and tobacco products instead of menthol cigarettes: A qualitative study of people who smoke menthol cigarettes in the United States.

The US Food and Drug Administration is considering banning menthol cigarettes, which could result in some people who smoke menthol cigarettes switching to other tobacco products (OTPs). This qualitative study explored reactions to using OTPs instead of menthol cigarettes. People who smoke menthol cigarettes (N=40) completed a behavioral economic assessment of the effects of menthol cigarette price increases on OTP purchasing. At the highest price, most participants could not afford menthol cigarettes. Instead, they could purchase non-menthol cigarettes, little cigars/cigarillos (LCCs), e-cigarettes, smokeless tobacco, or medicinal nicotine, or they could abstain from tobacco use. Participants used the OTPs they purchased for three days. During follow-up sessions, participants (n=35) completed semi-structured interviews discussing their purchasing-decisions and experiences using OTPs instead of menthol cigarettes. Interviews were analyzed using reflexive thematic analysis methods. Factors influencing purchasing decisions included flavor, price, prior use of OTPs, interest in trying new OTPs, and perceived ability to satisfy nicotine cravings. Participants described positive experiences using e-cigarettes including the "refreshing" menthol flavor, ability to use in places where cigarettes are prohibited, and convenience of use relative to smoking. Among those using non-menthol cigarettes, many reported they were acceptable but less satisfying products compared to menthol cigarettes while others reported negative reactions to them such as tasting like "cardboard". Reactions to smoking LCCs were mostly unfavorable but participants said it gave them "something to light". Multiple considerations may affect switching to OTPs in light of pending menthol cigarette regulation including the availability of menthol-flavored alternatives and (dis)satisfaction with OTPs.

Qualitative reactions to a low nicotine product standard for cigarettes from adolescents and young adults living in the United States who smoke.

The Biden Administration is considering a low nicotine product standard for cigarettes. This qualitative study examined reactions to a nicotine reduction policy among adolescents and young adults (AYA) who smoke cigarettes. After completing a lab study involving masked exposure either to low nicotine or normal nicotine research cigarettes and unmasked exposure to e-cigarettes varying in nicotine concentration and flavor, we conducted follow-up semi-structured interviews (N = 25) to explore participants' knowledge, attitudes, and perceptions of a low nicotine product standard and their anticipated tobacco use behavior after policy implementation. Interviews were audio-recorded, transcribed verbatim, double-coded, and analyzed using reflexive thematic analysis. Nearly half of participants supported the policy because they thought it would prevent young people from starting smoking and/or would help people quit. Reasons some participants opposed the policy included beliefs that adults should have the choice to smoke or that a nicotine reduction policy is counterintuitive because the government benefits from cigarette sales. Others believed the policy would be ineffective because youth could circumvent the policy (e.g., illicit market) or would increase their smoking to maintain the same nicotine level. Almost half of participants said they would quit smoking while the other half said they would continue smoking, although potentially reduce their smoking. Overall, our qualitative findings point to the need for pre-policy media campaigns targeting AYA who smoke to minimize negative reactions, dispel fears, and correct misperceptions as well as encourage quitting and provide information on accessing cessation resources.

The impact of the COVID-19 pandemic on a sample of US young adults who smoke cigarettes: A qualitative analysis.

INTRODUCTION: The ongoing COVID-19 pandemic has been associated with increased negative mood in youth, and a few reports of changes in tobacco use. We sought to increase the depth of knowledge on the effects of the pandemic on early young adult mood states, access to tobacco products and tobacco use behaviors, and knowledge of risks associated with tobacco use and COVID-19 by learning more about the lived experience of the pandemic among young adults early in their smoking trajectories. METHODS: Semi-structured qualitative interviews were conducted with 25 young adults ages 18-20 (M = 19) who smoked cigarettes daily or nearly every day and had used electronic cigarettes (ECs) on ≥ 2 occasions in their lifetime. RESULTS: Our results uncovered several themes: 1) The majority of teens experienced mental health disturbances as a result of the pandemic, which manifested as depression, anxiety, and/or acute loneliness due to social isolation; 2) tobacco purchasing behaviors sometimes changed, with both greater and less access reported among participants; 3) changes in tobacco use were also reported, with some reporting increases in use, others reporting decreases, and a few reporting quitting; and 4) while some youth reported that tobacco use could increase their risk related to COVID-19, the majority reported confusion and uncertainty about how tobacco use impacted their risk. CONCLUSIONS: The themes identified specific factors that may account for the heterogeneity of impacts of the pandemic on tobacco use, and highlight the value of qualitative work for centering the lived experience of youth for understanding larger trends in substance use.

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

BACKGROUND: A 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. METHODS: We 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. RESULTS: Concurrent 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. CONCLUSIONS: Should 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.

COVID-19-Related Stressors and Clinical Mental Health Symptoms in a Northeast US Sample.

Research has linked specific COVID-19-related stressors to the mental health burden, yet most previous studies have examined only a limited number of stressors and have paid little attention to their clinical significance. This study tested the hypothesis that individuals who reported greater COVID-19-related stressors would be more likely to have elevated levels of anxiety, posttraumatic stress symptoms, and serious psychological distress. METHODS: An online survey was administered to a convenience sample from 18 June to 19 July 2020, in US states that were most affected by COVID-19 infections and deaths at the time. Individuals who were 18 or older and residents of five Northeast US states were eligible to participate (N = 1079). In preregistered analyses, we used logistic regression models to test the associations of COVID-19 stressors with symptoms on the Generalized Anxiety Disorder-7 (GAD-7), Impact of Event Scale-Revised, and K6, adjusting for sociodemographic covariates. RESULTS: COVID-19-related stressors (i.e., essential worker status, worry about COVID-19 infection, knowing someone hospitalized by COVID-19, having children under 14 at home, loneliness, barriers to environmental rewards, food insecurity, loss of employment) were associated with meeting thresholds (i.e., positive screening) for anxiety, posttraumatic stress, and/or serious psychological distress. Loneliness and barriers to environmental rewards were associated with all mental health outcomes. LIMITATIONS: We used a non-probability sample and cannot assume temporal precedence of stressors with regard to development of mental health symptoms. CONCLUSIONS: These findings link specific stressors to the mental health burden of the COVID-19 pandemic.

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

AIM: While 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. METHODS: A 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 (eg social distancing, mask wearing) were examined. RESULTS: Among 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 versus 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). CONCLUSIONS: Smoking 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. IMPLICATIONS: Individuals 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.

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

INTRODUCTION: 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. AIMS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. IMPLICATIONS: 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).

The Impact of Reducing Nicotine Content on Adolescent Cigarette Smoking and Nicotine Exposure: Results From a Randomized Controlled Trial.

INTRODUCTION: As the science base around the potential benefits of a reduced-nicotine standard for cigarettes grows, information on the potential effects on adolescent smokers is a high priority. The aim of this randomized trial was to test the influence of 3-week exposure to reduced nicotine cigarettes in a sample of adolescent daily smokers. AIMS AND METHODS: In this double-blind, two-arm, randomized controlled trial (NCT0258731), following a 1-week baseline, adolescent daily smokers not currently intending to quit (ages 15-19 years, n = 66 randomized) were urn randomized to use either very low nicotine content (VLNC; 0.4 mg/g; n = 33) or normal nicotine content (NNC, 15.8 mg/g; n = 33) research cigarettes for 3 weeks. Participants attended five study sessions at our clinical laboratory. The primary outcome was average total cigarettes smoked per day (CPD; including both study and non-study cigarettes) at week 3. RESULTS: Stepwise regression results demonstrated that compared with NNC cigarettes (n = 31), assignment to VLNC cigarettes (n = 29), was associated with 2.4 fewer CPD on average than NNC assignment (p < .05) week 3 when controlling for covariates (p < .01, Cohen's d = 0.52 n = 60 completed all procedures). VLNC cigarettes were also associated with lower levels of craving reduction than NNC cigarettes (Questionnaire on Smoking Urges Factor 2, p < .05). No group differences were found for secondary outcomes. CONCLUSIONS: Adolescent participants assigned to VLNC use for 3 weeks smoked fewer total CPD relative to the NNC group. Overall, data suggest that a VLNC policy would reduce cigarette smoking in adolescents who smoke, but high rates of incomplete adherence suggest that youth may seek alternative sources of nicotine in this scenario. IMPLICATIONS: The US 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 adolescents who smoke. This study, the first clinical trial of VLNC cigarettes in adolescents, demonstrates that adolescents switched to VLNC cigarettes for 3 weeks reduced their CPD relative to the normal-nicotine cigarette control group, without leading to increased respiratory symptoms or increased withdrawal. Biomarkers indicated the use of other sources of nicotine, suggesting that such a policy will need to consider approaches to assist in transitioning away from smoking.