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Introduction: The Biden administration is pursuing a nicotine reduction policy in the United States 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., Aims and Methods: Adolescents who smoke cigarettes daily (ages 15-19; N = 60) were enrolled in a 3-week double-blind randomized clinical trial and assigned to smoke either normal nicotine content 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 United States., 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 on 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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 laboratory study. After sampling each product, participants completed the cigarette purchase task (CPT) and modified cigarette evaluation questionnaire (mCEQ). Following 1 week of substituting their preferred MCA for their UBMC, participants completed a 90-minute concurrent-choice self-administration (SA) task comparing their UBMC and preferred MCA. Linear regression models explored associations between CPT demand indices and mCEQ subjective effects in the laboratory 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), price associated with maximal expenditure (Pmax) (p = .04), maximal expenditure (Omax) (p = .03), and breakpoint (p = .03). Subjective effects captured by the mCEQ were not associated with response effort., Conclusions: Demand indices reflecting Persistence (ie, 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 (ie, addiction potential) of combustible tobacco products similar to the longer SA 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 CPT efficiently capture information on the relative reinforcing value of UBMC and plausible alternative tobacco products, similar to a 90-minute in-laboratory SA task., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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.

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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).

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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).

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Public 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., Methods: Adolescents 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., Results: An 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 (O max ) 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)., Conclusions: A 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., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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 Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Conflict of Interest The authors have no conflicts to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

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.

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We examined if the relative-reinforcing effects of smoking increase with greater cumulative vulnerability and whether cumulative vulnerability moderates response to reduced nicotine content cigarettes. Participants were 775 adults from randomized clinical trials evaluating research cigarettes differing in nicotine content (0.4, 2.4, 15.8 mg/g). Participants were categorized as having low (0-1), moderate (2-3), or high (≥4) cumulative vulnerability. Vulnerabilities included rural residence, opioid use disorder, affective disorder, low educational attainment, poverty, unemployment, and physical disability. We used the cigarette purchase task (CPT) to assess the relative-reinforcing effects of participants' usual-brand cigarettes at baseline and study cigarettes during the 12-week trial. The CPT is a behavioral-economic task wherein participants estimate likely smoking (demand) over 24 h under escalating cigarette price. Demand is characterized by two factors: Amplitude (demand volume at zero/minimal price) and Persistence (demand sensitivity to price). Greater cumulative vulnerability was associated with greater demand Amplitude (F[2709] = 16.04,p < .0001) and Persistence (F[2709] = 8.35,p = .0003) for usual-brand cigarettes. Demand Amplitude for study cigarettes increased with increasing cumulative vulnerability (F[2619] = 19.59, p < .001) and decreased with decreasing nicotine content ([4879] = 5.45, p < .001). The only evidence of moderation was on demand Persistence (F[8867] = 2.00,p = .04), with larger reductions at the 0.4 mg/g compared to 15.8 mg/g doses among participants with low compared to moderate or high cumulative vulnerability. The relative-reinforcing effects of smoking clearly increase with greater cumulative vulnerability. Reducing nicotine content would likely reduce demand Amplitude across cumulative-vulnerability levels but reductions in demand Persistence may be more limited among those with greater cumulative vulnerability., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Inc.)

A national nicotine reduction policy has the potential to reduce cigarette smoking and associated adverse health impacts among vulnerable populations. However, possible unanticipated adverse effects of reducing nicotine content in cigarettes, such as increasing the use of alcohol or other abused substances, must be examined. The purpose of this study was to evaluate the effects of exposure to varying doses of nicotine in cigarettes on use of other substances. This was a secondary analysis (n = 753) of three simultaneous, multisite, double-blind, randomized-controlled trials examining 12 weeks of exposure to study cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) among daily smokers from three vulnerable populations: individuals with affective disorders (n = 251), individuals with opioid use disorder (n = 256), and socioeconomically-disadvantaged women of reproductive age (n = 246). Effect of study cigarette assignment on urine toxicology screens (performed weekly) and responses to drug and alcohol use questionnaires (completed at study weeks 6 and 12) were examined using negative binomial regression, logistic regression, or repeated measures analysis of variance, controlling for sex, age, and menthol status. The most common substances identified using urine toxicology included tetrahydrocannabinol (THC; 44.8%), cocaine (9.2%), benzodiazepine (8.6%), and amphetamines (8.0%), with 57.2% of participants testing positive at least once for substance use (27.3% if excluding THC). No significant main effects of nicotine dose were found on any of the examined outcomes. These results suggest that reducing nicotine content does not systematically increase use of other substances, even among individuals at increased risk of substance use. ClinicalTrials.gov Identifiers: NCT02232737, NCT2250664, NCT2250534., Competing Interests: Declaration of Competing Interest Dr. Hughes has received consulting and speaking fees from several companies that develop or market pharmacological and behavioral treatments for smoking cessation or harm reduction and from several non-profit organizations that promote tobacco control. He has recently received consulting fees from Swedish Match, Altria and Philip Morris International to assist their efforts to develop less risky tobacco products. All other authors have no disclosures to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Cigarette smoking is overrepresented in populations with psychiatric conditions and socioeconomic disadvantage. Greater understanding of the role of reinforcement and nicotine dependence in smoking among vulnerable populations may facilitate development of better targeted interventions to reduce smoking. Prior research demonstrated that individual differences in the reinforcing value of smoking and nicotine-dependence severity predicted total nicotine-exposure in vulnerable populations. The present study uses multivariate regression to address two aims: (1) Quantify the degree to which the reinforcing value of smoking, assessed using the Cigarette Purchase Task (CPT), and dependence severity assessed using the Fagerström Test of Nicotine Dependence and Brief Wisconsin Inventory of Smoking Dependence Motives (B-WISDM) each account for individual differences in cotinine-plus-3'-hydroxycotinine (COT+3HC) levels. (2) Explore whether there is overlap in the variance accounted for by the CTP, FTND, and B-WISDM. Participants were 628 adults with co-morbid psychiatric conditions or socioeconomic disadvantage who smoked daily. The CPT, FTND, and B-WISDM models accounted for 23.76%, 32.45%, and 29.61% of the variance in COT+3HC levels, respectively. Adding CPT to the FTND model failed to increase the variance accounted for and adding it to the B-WISDM model did so by only 1.2% demonstrating considerable overlap in the variance in nicotine exposure levels accounted for by these three instruments. These results provide new knowledge on the relationship between individual differences in the reinforcing value of smoking and nicotine-exposure levels and suggest differences in reinforcing value may underpin a considerable portion of the variance in nicotine exposure accounted for by dependence severity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Background: Among 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., Methods: After 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., Results: At 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., Conclusion: A nicotine reduction policy may reduce cigarette reinforcement in this vulnerable population., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Hypothetical purchase tasks have been widely used to assess the reinforcing value of tobacco products. However, a task has not yet been validated for little cigars and cigarillos (LCCs), a popular tobacco product class among vulnerable populations. This study sought to validate the LCC Purchase Task (LCCPT) in a sample of experienced LCC smokers., Methods: Data were collected from 65 young adult (18-34 years) LCC and cigarette dual users (78.5% male) in Connecticut (2018-2020). Participants completed the usual-brand LCCPT for consumption in 24 h at increasing prices. We calculated four observed demand indices: intensity (consumption at $0), breakpoint (price after which consumption reaches 0), O max (maximum daily expenditure), and P max (price at which daily expenditure was maximized). Two indices were estimated from demand curves: Q 0 (predicted consumption as price approaches $0) and price-sensitivity (sensitivity to price increases). Spearman correlations and multivariable regressions examined the associations between demand indices, self-reported cigar use, and dependence., Results: Correlations were in expected directions. All indices except breakpoint and P max were positively correlated with use, and all indices were correlated with multiple measures of dependence. Overall, greater demand and expenditure for LCCs and lower sensitivity to price changes were correlated with greater use and dependence. In regression analyses intensity and price-sensitivity showed the strongest relationships with use and dependence., Conclusions: The validity of the LCCPT was supported in a sample of experienced LCC smokers. This instrument can be incorporated into other protocols to assess the abuse liability of LCCs., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Reducing the nicotine content of cigarettes is a promising policy intervention to decrease cigarette dependence among people who smoke. Randomized trials support the potential efficacy of a reduced nicotine product standard for cigarettes. However, interpretation of such trials is challenged by incomplete adherence to the randomized treatment assignment, as some participants may continue to use commercial cigarettes not provided by the trial. The current study examined prevalence and predictors of non-adherence among trial participants with serious mental illness (SMI)., Aims and Methods: Adults with SMI who smoke daily and were not trying to quit (N = 58) were randomized to receive very low nicotine content (VLNC) or normal nicotine content cigarettes over 6 weeks. We investigated predictors of biologically assessed non-adherence in participants assigned to VLNC cigarettes (n = 30). Predictors included subjective responses to VLNC cigarettes, baseline nicotine dependence and dependence motives, and psychiatric symptom severity. We fit a series of linear models regressing non-adherence metrics onto covariates (gender; menthol preference) and focal predictors., Results: Nearly all participants (96%) were estimated to be less than completely adherent to VLNC cigarettes. Lower enjoyment ratings of respiratory tract sensations of VLNC cigarettes predicted a greater degree of non-adherence (b = -.40, SE = .14, 95% CI: -0.71, -0.10)., Conclusions: Less positive subjective response to smoking VLNC cigarettes was the only significant predictor of incomplete adherence among individuals with SMI, consistent with prior research in a general population sample. This suggests the potential for shared strategies to help different smoking populations adjust to a reduced nicotine product standard., Implications: Results offer preliminary insight into potential barriers to adherence in SMI populations. Adherence might be enhanced by supplementing VLNC cigarettes with alternative sources of non-combusted nicotine, paired with educational campaigns to encourage quitting or switching to less harmful products. Future studies should replicate these analyses in a larger sample of individuals with SMI who smoke., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Misperceptions about nicotine's contribution to smoking-related health harms could complicate efforts to reduce the public health burden of smoking. Study goals were to describe nicotine knowledge among adults who smoke and investigate whether misperceiving nicotine as a source of health harm was associated with beneficial health behaviors, or lower uptake of using less harmful sources of nicotine to support smoking cessation attempts., Method: This study used longitudinal data from 9140 adults who participated in four waves of the Population Assessment of Tobacco and Health Study and were current smokers during the first wave. Logistic regressions estimated odds ratios for correct responses across six aspects of nicotine knowledge assessed in Wave 4. Longitudinal models estimated associations between misperceptions and cigarette consumption, and odds of making a quit attempt; self-reported cessation; e-cigarette use; and use of NRT or e-cigarettes to support quit attempts., Results: Participants who were non-White, older, and had lower educational attainment or income tended to be least knowledgeable about nicotine. Misperceiving nicotine as harmful to health was associated with increased odds of quit attempts (AOR: 1.12, 95% CI: 1.03, 1.23), lower odds of cessation success (AOR: 0.84, 95% CI: 0.73, 0.98) and e-cigarette use (AOR: 0.79, 95% CI: 0.72, 0.86), and lower odds of using NRT (AOR: 0.84, 95% CI: 0.71, 0.99) or e-cigarettes to support quit attempts (AOR: 0.59, 95% CI: 0.49, 0.71)., Conclusion: Harm reduction efforts may be impeded by misperceptions about nicotine. Further work should evaluate the effects of correcting such misperceptions through public education., Implications: This study provides longitudinal evidence that among adult smokers, misperceiving nicotine as a primary cause of smoking-related diseases may be associated with reduced cessation success and lower likelihood of using less harmful nicotine products. These misperceptions may therefore impede efforts to encourage smokers ready to quit to use evidence-based cessation support such as nicotine replacement during quit attempts and limit the success of policies designed to shift smokers to less harmful sources of nicotine. Further work should evaluate the longitudinal effects of correcting nicotine misperceptions through public education targeted toward adults who smoke., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The US Food and Drug Administration recently announced its intention to pursue a federal ban on menthol cigarettes. This qualitative study assessed reactions to a potential menthol cigarette ban among people who smoke menthol cigarettes., Methods: As part of a laboratory study examining menthol flavor regulations, we conducted follow-up interviews with participants who smoke menthol cigarettes (N = 35). We explored the following topics: (1) menthol cigarette risk perceptions; (2) knowledge, attitudes, and perceptions of menthol cigarette regulations; and (3) anticipated behavior if menthol cigarettes were banned. Interviews were audio-recorded, transcribed verbatim, double-coded, and analyzed using reflexive thematic analysis., Results: Many participants thought menthol cigarettes carried more health risks than non-menthol cigarettes. Some participants said regulators wanted to ban menthol cigarettes because they appeal to youth. Others thought a ban would be good for public health because fewer people, particularly youth, would smoke. Several voiced skepticism about banning only menthol cigarettes rather than all cigarettes. Most said they would use other products, including electronic cigarettes or non-menthol cigarettes, but many also thought a menthol ban could motivate them or others to quit smoking., Conclusions: Banning menthol cigarettes could lead some people who smoke menthol cigarettes to switch to potentially less harmful products, like e-cigarettes, or quit smoking, which would likely benefit public health; however, others may simply transition to non-menthol cigarettes. As regulators move forward with banning menthol cigarettes, communication campaigns explaining the public health benefits, potentially focusing on the benefits for youth, should be part of the policy implementation plan., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: This study examined whether exposure to reduced-nicotine-content cigarettes (RNCCs) for 12 weeks alters respiratory health using Fractional Exhaled Nitric Oxide (FeNO), a validated biomarker of respiratory epithelial health, and the Respiratory Health Questionnaire (RHQ), a subject-rated questionnaire on respiratory symptoms. Participants were 747 adult daily smokers enrolled in three double-blind, randomized clinical trials evaluating effects of cigarette nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) in people with affective disorders, opioid use disorder (OUD), or socioeconomic disadvantage., Aims and Methods: FeNO levels and RHQ ratings were collected at baseline and Weeks 6 and 12 following randomization. Multiple regression was used to assess associations of FeNO and RHQ with smoking characteristics. Mixed-model repeated-measures ANOVA was used to evaluate the effects of nicotine content on FeNO and RHQ outcomes over the 12-week study period., Results: FeNO levels but not RHQ ratings varied inversely with smoking characteristics at baseline (Ps < 0.0001) in smokers with affective disorders and socioeconomic disadvantage but less so in those with OUD. Participants with affective disorders and socioeconomic disadvantage, but not those with OUD, who were assigned to RNCCs had higher FeNO levels at Week 12 than those assigned to the 15.8 mg/g dose [F(2,423) = 4.51, p = .01, Cohen's d = 0.21]. No significant dose-related changes in RHQ scores were identified., Conclusions: Use of RNCCs across a 12-week period attenuates smoking-related reductions in FeNO levels in smokers with affective disorders and socioeconomic disadvantage although not those with OUD. FeNO changes were not accompanied by changes in respiratory-health ratings., Trial Registration: Inclusion and exclusion criteria for the sample and experimental manipulation of the nicotine content of assigned cigarettes are registered: NCT02232737, NCT02250664, NCT02250534. The FeNO measure reported in this manuscript is an exploratory outcome that was not registered., Implications: Should a reduced nicotine content standard be implemented; these results suggest that reduced nicotine content in cigarettes will not exacerbate and instead may attenuate smoking-related decreases in FeNO. This is significant as NO is an important component in maintaining a healthy respiratory system and necessary to defend against infection. Furthermore, the results of the current study demonstrate that the adoption of the reduced nicotine content standard may result in beneficial impacts on respiratory epithelial health among vulnerable populations that are disproportionally affected by the adverse health outcomes precipitated by combustible tobacco use., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Substance use is a risk factor for COVID-19 infection and adverse outcomes. However, reasons for elevated risk for COVID-19 in substance users are not well understood., Objective: The aim of this study was to evaluate whether alcohol or other drug use is associated with adherence to Centers for Disease Control and Prevention (CDC) guidelines for COVID-19 mitigation. Preregistered analyses tested the hypothesis that greater use of alcohol and other drugs would be associated with lower CDC guideline adherence. A secondary objective was to determine whether substance use was associated with the likelihood of COVID-19 testing or outcome., Methods: A cross-sectional web-based survey was administered to a convenience sample recruited through Amazon's Mechanical Turk platform from June 18 to July 19, 2020. Individuals aged 18 years or older and residing in Connecticut, Massachusetts, New Jersey, New York, or Rhode Island were eligible to participate. The exposure of interest was past 7-day use of alcohol, cigarettes, electronic cigarettes, cannabis, stimulants, and nonmedical opioids. The primary outcome was CDC guideline adherence measured using a scale developed from behaviors advised to reduce the spread of COVID-19. Secondary outcomes were likelihood of COVID-19 testing and a positive COVID-19 test result. All analyses accounted for the sociodemographic characteristics., Results: The sample consisted of 1084 individuals (mean age 40.9 [SD 13.4] years): 529 (48.8%) men, 543 (50.1%) women, 12 (1.1%) other gender identity, 742 (68.5%) White individuals, 267 (24.6%) Black individuals, and 276 (25.5%) Hispanic individuals. Daily opioid users reported lower CDC guideline adherence than nondaily users (B=-0.24, 95% CI -0.44 to -0.05) and nonusers (B=-0.57, 95% CI -0.76 to -0.38). Daily alcohol drinkers reported lower adherence than nondaily drinkers (B=-0.16, 95% CI -0.30 to -0.02). Nondaily alcohol drinkers reported higher adherence than nondrinkers (B=0.10, 95% CI 0.02-0.17). Daily opioid use was related to greater odds of COVID-19 testing, and daily stimulant use was related to greater odds of a positive COVID-19 test., Conclusions: In a regionally-specific, racially, and ethnically diverse convenience sample, adults who engaged in daily alcohol or opioid use reported lower CDC guideline adherence for COVID-19 mitigation. Any opioid use was associated with greater odds of COVID-19 testing, and daily stimulant use was associated with greater odds of COVID-19 infection. Cigarettes, electronic cigarettes, cannabis, or stimulant use were not statistically associated with CDC guideline adherence, after accounting for sociodemographic covariates and other substance use variables. Findings support further investigation into whether COVID-19 testing and vaccination should be expanded among individuals with substance-related risk factors., (©Mollie A Monnig, Hayley Treloar Padovano, Alexander W Sokolovsky, Grace DeCost, Elizabeth R Aston, Carolina L Haass-Koffler, Claire Szapary, Patience Moyo, Jaqueline C Avila, Jennifer W Tidey, Peter M Monti, Jasjit S Ahluwalia. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 09.11.2021.)

Risk for smoking increases in a summative manner corresponding to the number of co-occurring vulnerabilities present (cumulative vulnerability). We examined whether cumulative vulnerabilities moderate response to reduced nicotine content cigarettes in a secondary analysis of results from 775 participants in three 12-week randomized clinical trials examining research cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco). Participants were categorized as having 0-1, 2-3, or ≥ 4 cumulative vulnerabilities. Vulnerabilities included: rural residence, current substance use disorder, current affective disorder, low educational attainment, poverty, unemployment, physical disability. The primary outcome was total cigarettes per day (CPD) during Week 12; secondary outcomes included CPD across weeks, toxin exposure, dependence severity, craving/withdrawal (17 dependent measures). Results were analyzed using repeated measures analysis of covariance and growth-curve modeling. Total CPD during Week 12 increased as cumulative-vulnerability increased (P = 0.004), and decreased as nicotine content decreased (P < 0.001), with no significant interaction of cumulative vulnerability and dose (P = 0.67). Effects on other outcomes generally followed that same pattern. The only exception across the other outcomes was on Questionnaire-on-Smoking-Urges Factor-2 ratings for usual-brand cigarettes where cumulative vulnerability, dose, and time interacted (P = 0.007), with craving at the 0.4 and 2.4 mg/g doses decreasing over time, but inconsistently across vulnerability categories. Overall, we saw little evidence that cumulative vulnerabilities moderate response to reduced nicotine content cigarettes suggesting that a policy reducing nicotine content in cigarettes to minimally addictive levels could benefit even highly vulnerable smokers including those residing in rural or other regions with overrepresentation of co-occurring vulnerabilities. Clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: As the FDA works to determine whether a nicotine reduction policy would benefit public health, one key question is whether to mandate an immediate or gradual reduction in nicotine levels in cigarettes. The aim of this study was to determine whether the effects of gradual versus immediate nicotine reduction on cigarettes per day (CPD), total nicotine equivalents, and subjective responses differed in younger adults versus older adults., Methods: Using data from a recent randomized trial conducted in the United States (N = 1250) that switched smokers over a 20-week period to very low nicotine content (VLNC) cigarettes either immediately, gradually (via monthly reductions in nicotine content), or not at all (control condition, normal nicotine content research cigarette), we analyzed the moderating effect of age (age 18-24 or 25+)., Results: For both age groups, CPD in the immediate condition was significantly lower relative to gradual condition (estimated mean difference of 6.3 CPD in young adults, 5.2 CPD in older adults; p's < .05). Younger and older adults in the immediate and gradual reduction conditions had lower total nicotine equivalents at Week 20 (all p's < .05) than those in the control condition; age group did not moderate this effect. Positive subjective responses to cigarettes were lower among young adults relative to older adults in the immediate condition., Conclusions: These results indicate that an immediate reduction in nicotine would result in beneficial effects in both young and older adults. Young adults show less positive subjective effects of smoking following switching to VLNC cigarettes relative to older adults., Implications: As researchers work to understand how a potential reduced-nicotine product standard for cigarettes may affect public health, one question is whether nicotine should be reduced immediately or gradually. This study demonstrates that both young and older adults who were switched immediately to the lowest content of nicotine smoked fewer CPD and had lower nicotine intake than those in the gradual condition. Furthermore, young adults appear to show lower positive subjective effects following switching to VLNC cigarettes relative to older adults. This is consistent with previous work demonstrating that young people appear to show lower abuse liability for VLNC cigarettes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Lowering nicotine in cigarettes may reduce smoking prevalences; however, it is not known whether an immediate or gradual reduction in nicotine is the optimal approach for all population groups., Objectives: We examined whether the optimal approach to nicotine reduction depended on the education, gender, or race of people who smoke and whether the optimal approach differentially benefited people who smoke based on their education, gender, or race., Methods: Secondary analysis was conducted on a randomized clinical trial (N = 1250) comparing (1) immediate reduction from 15.5 to 0.4 mg of nicotine per gram of tobacco(mg/g);(2) gradual reduction to 0.4 mg/g;(3) control group with normal nicotine cigarettes(15.5 mg/g). Outcomes included cigarettes per day(CPD), carbon monoxide(CO), total nicotine equivalents(TNE), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides(NNAL), phenanthrene tetraol(PheT), N-Acetyl-S-(2-cyanoethyl)-l-cysteine(CEMA). Data were analyzed as area under the curve(AUC)., Results: Results were presented by education (High school[HS] or less n = 505, more than HS n = 745), gender (males n = 701, females n = 549), and race (Black participants n = 373,White participants n = 758). Regardless of education, gender, and race, CPD, CO, TNE, NNAL, PheT, and CEMA were lower in immediate versus gradual nicotine reduction. Comparing immediate versus the control, outcomes were lower for all subgroups; however, the magnitude of the effect for TNE varied by race. Specifically, geometric mean of the AUC of TNE in immediate versus gradual was 49 % lower in Black participants and 61 % lower in White participants (p-value = 0.047)., Conclusions: Immediately reducing nicotine in cigarettes has the potential to benefit people who smoke across lower and higher educational attainment, male and female gender, and Black and White race., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: A nicotine product standard reducing the nicotine content in cigarettes could improve public health by reducing smoking. This study evaluated the potential unintended consequences of a reduced nicotine product standard by examining its effects on (1) smoking behaviors based on drinking history; (2) drinking behavior; and (3) daily associations between smoking and drinking., Methods: Adults who smoke daily (n = 752) in the United States were randomly assigned to smoke very low nicotine content (VLNC) cigarettes versus normal nicotine content (NNC; control) cigarettes for 20 weeks. Linear mixed models determined if baseline drinking moderated the effects of VLNC versus NNC cigarettes on Week 20 smoking outcomes. Time-varying effect models estimated the daily association between smoking VLNC cigarettes and drinking outcomes., Results: Higher baseline alcohol use (vs no use or lower use) was associated with a smaller effect of VLNC on Week 20 urinary total nicotine equivalents (ps < .05). No additional moderation was supported (ps > .05). In the subsample who drank (n = 415), in the VLNC versus NNC condition, daily alcohol use was significantly reduced from Weeks 17 to 20 and odds of binge drinking were significantly reduced from Weeks 9 to 17. By Week 7, in the VLNC cigarette condition (n = 272), smoking no longer predicted alcohol use but remained associated with binge drinking., Conclusions: We did not support negative unintended consequences of a nicotine product standard. Nicotine reduction in cigarettes generally affected smoking behavior for individuals who do not drink or drink light-to-moderate amounts in similar ways. Extended VLNC cigarette use may improve public health by reducing drinking behavior., Implications: There was no evidence that a VLNC product standard would result in unintended consequences based on drinking history or when considering alcohol outcomes. Specifically, we found that a very low nicotine standard in cigarettes generally reduces smoking outcomes for those who do not drink and those who drink light-to-moderate amounts. Furthermore, an added public health benefit of a very low nicotine standard for cigarettes could be a reduction in alcohol use and binge drinking over time. Finally, smoking VLNC cigarettes may result in a decoupling of the daily associations between smoking and drinking., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Background: We conducted a psychometric analysis of an adapted secondhand smoke (SHS) questionnaire by testing the three-component structure of the original scale that measures SHS exposure in home, work and social environments., Methods: The 15-item questionnaire was administered to 839 daily smokers participating in a multi-site randomized controlled trial. Following parallel analysis, we conducted a confirmatory factor analysis specifying a three-factor structure. Cronbach's alphas and fit indices were calculated to assess internal consistency. Criterion validity was assessed by comparing the Social environments subscale to the Brief Wisconsin Inventory of Smoking Dependence Motives Social/Environmental Goads subscale. Predicative validity of the questionnaire was assessed using linear regressions and tobacco biomarkers of harm; NNAL, expired carbon monoxide and total cotinine., Results: Five items did not load onto any factor and were dropped, resulting in a 10-item questionnaire. The Cronbach's alphas were (0.86), (0.77) and (0.67) for the Work, Social, and Home subscales, respectively. The WISDM subscale was moderately correlated with scores on the Social subscale (r = 0.57, p < 0.001). The questionnaire demonstrated predictive validity of smoke exposure above individual's own reported use as measured by cigarettes smoked per day., Conclusions: Three constructs emerged; results indicate that a shortened 10-item scale could be used in future studies.

The Center for Addiction and Disease Risk Exacerbation (CADRE) is a COBRE establishing a thematically linked, state-of-the-art, multidisciplinary Center investigating mechanisms where-by substance use (SU) increases the risk for or exacerbates chronic disease. It does so by employing a combination of behavioral and physiological laboratory-based approaches across several substances and across several diseases. COBRE projects investigate mechanisms underlying effects of opioids, cannabis, tobacco, and alcohol on risks for and progression of SU-related disease. Though linkages between SU and disease are well documented, physiological mechanisms underlying such associations are poorly understood, mainly because published studies use cross-sectional designs that do not allow for causal interpretations. Mechanisms studied in CADRE projects include systemic inflammation, immune system dysregulation, high blood pressure, pulmonary effects, and carcinogen exposure. A Clinical Laboratory Core provides infrastructure, resources, and scientific expertise and a center-wide database of risk factors associated with the development of SU and chronic disease.

Introduction: The Food and Drug Administration is considering a policy to drastically reduce the allowable nicotine content of cigarettes. The current study examined whether the policy implementation approach, i.e., either immediately reducing nicotine content to very low levels or gradually reducing nicotine content over an extended period, influences policy support among people who smoke cigarettes., Methods: Adults who smoked daily were randomly assigned (double-blind) to an immediate nicotine reduction condition (0.4 mg/g nicotine cigarettes), a gradual nicotine reduction condition (15.5 to 0.4 mg/g), or a control condition (15.5 mg/g) for 20 weeks. Participants were asked if they would "support or oppose a law that reduced the amount of nicotine in cigarettes, to make cigarettes less addictive." Logistic regression analyses assessed if policy support was affected by treatment condition, demographic covariates, interest in quitting, and subjective cigarette effects., Results: At Week 20 (N = 957 completers), 60.4% of participants supported the policy, 17.4% opposed, and 22.2% responded "Don't know." Policy support did not differ by treatment condition. Support was greater among those interested in quitting (OR = 3.37, 95% CI = 2.49, 4.55). Support was lower among males (OR = 0.49, 95% CI = 0.37, 0.67), those with greater dependence scores (OR = 0.92, 95% CI = 0.86, 0.99) and participants aged 18-24 (OR = 0.53, 95% CI = 0.28, 0.99). No other covariates were associated with policy support., Conclusions: The majority of participants supported a nicotine reduction policy. The implementation approach, immediate or gradual reduction, did not affect policy support. Participants interested in quitting smoking were more likely to support a nicotine reduction policy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Menthol cigarette smokers may switch to other combusted products like menthol little cigars and cigarillos (LCCs) or switch to non-combusted products like menthol vapes if menthol cigarettes are banned or otherwise restricted. This pilot study used a behavioral economics task to understand (a) menthol cigarette demand across a range of increasing prices in the context of available alternative products and (b) how the availability of menthol LCCs affected cigarette demand and alternative product substitution., Methods: Menthol smokers completed the Experimental Tobacco Marketplace task during two sessions. Cigarettes, LCCs, smokeless tobacco, vapes, and medicinal nicotine were available from an online store. The price of menthol cigarettes increased across trials while the prices of the alternative products remained constant. Menthol LCCs were available in one session and excluded in the other. Cross-price elasticity beta estimates identified significant product substitutes., Results: When menthol LCCs were available, increasing the price of menthol cigarettes led to substitution with non-menthol cigarettes (β = 0.65, 95%CI = 0.34, 0.96), menthol little cigars (β = 0.39, 95%CI = 0.08, 0.70), and menthol vapes (β = 0.26, 95%CI = 0.16, 0.35). When menthol LCCs were not available, increasing the price of menthol cigarettes led to substitution with non-menthol cigarettes (β = 0.59, 95% CI = 0.08, 1.11), non-menthol cigarillos (β = 0.62, 95%CI = 0.19, 1.04), and menthol vapes (β = 0.13, 95%CI = 0.08, 0.18)., Conclusions: As the price of menthol cigarettes increased, demand for menthol cigarettes decreased and demand for combusted and non-combusted products increased, indicating significant substitution for menthol cigarettes. Policies targeting menthol combusted tobacco could result in some menthol smokers switching to non-combusted products like vaping devices., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Exclusive e-cigarette use has been shown to be associated with reduced levels of respiratory symptoms relative to smoking combustible cigarettes; this association has been less frequently studied in smokers using advanced-generation e-cigarette devices. Advanced-generation devices generate denser vapor than either early generation or pod-style devices, and engender longer inhalations; these vaping topography patterns may contribute to respiratory symptoms., Methods: In a single-session, cross-sectional study of exclusive e-cigarette users (N = 59) and dual users of e-cigarettes and cigarettes (N = 54), participants completed questionnaires, including the American Thoracic Society Questionnaire (ATSQ) and were videotaped vaping their own device in the lab for 1 hour. Using a hierarchical regression method, we examined whether topography variables, level of nicotine concentration used in their e-cigarette device in the past month, e-cigarette dependence, amount of e-cigarette use in the past month, and smoking status (any smoking in the last month vs. none) predicted ATSQ score severity., Results: There was a significant mean difference in ATSQ score across smoking status, with greater ATSQ scores for vapers who also smoked cigarettes (19.0, SD = 6.7) than for exclusive vapers (13.4, SD = 5.3). In the final model, of the predictors of interest, only cigarette smoking status predicted significantly greater ATSQ scores (overall F = 2.51, p = .006; R2 = .26; smoking status β = 0.39, p < .0001)., Conclusions: Findings suggest that differences in respiratory symptoms between dual and exclusive e-cigarette users appear to be attributable to combustible cigarette smoking, rather than more intense or frequent e-cigarette use across groups., Implications: In this comparison of exclusive advanced-generation vape device users (N = 59) versus dual users of these devices and combustible cigarettes (N = 54), we set out to determine the extent to which smoking status and e-cigarette use variables predicted self-reported respiratory symptom severity. We found that dual users showed greater respiratory symptom severity (ATSQ scores) than exclusive vapers. Despite examining vaping topography and other variables, smoking status and race were the only significant predictor of respiratory symptoms. We conclude that combustible cigarette use, not individual vaping topography, likely accounts for differences in respiratory symptoms between dual users and exclusive vapers., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Individuals with opioid use disorder (OUD) have high prevalence of smoking and poor cessation outcomes. Data suggest that smokers with OUD may experience heightened nicotine reinforcement and more severe tobacco withdrawal compared to smokers without OUD. The Food and Drug Administration is currently considering reducing the nicotine content of cigarettes to reduce smoking prevalence and smoking-related disease. It is critical to understand the effects of reduced nicotine content cigarettes (RNCCs) on tobacco withdrawal in this subgroup. In this secondary analysis, we investigated the ability of RNCCs to attenuate acute tobacco withdrawal and craving severity in smokers with OUD versus those without substance use disorders (SUDs). Smokers maintained on methadone or buprenorphine (opioid-maintained [OM]; n = 65) versus without other SUDs (i.e., non-SUD; n = 135) completed 5 laboratory sessions wherein they smoked their usual brand (UB) or a research cigarette varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g of tobacco) under double-blind, acute abstinence conditions. Participants completed the Minnesota Tobacco Withdrawal Scale, including a desire to smoke (craving) item, before and every 15 min for 1 hr following smoking each cigarette. Tobacco withdrawal and craving did not differ significantly by OM status in response to UB or RNCCs. In addition to the Dose × Time interaction, greater depression and cigarette dependence consistently predicted withdrawal and craving (ps < .05). Across all cigarettes, tobacco withdrawal and craving did not significantly differ by OM status, suggesting that smokers receiving opioid agonist treatment may respond favorably to RNCCs. Additional studies with larger and more diverse samples are needed to address this question more definitively. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

We examined whether elucidating underpinning smoking motivation and related pharmacological processes enhances understanding of nicotine dependence among smokers from vulnerable populations. Data were obtained between Oct, 2016 and Sept, 2019 from 745 adult smokers with co-morbid psychiatric conditions or socioeconomic disadvantage at University of Vermont, Brown University, Johns Hopkins University. Smoking motivation was assessed using the Cigarette Purchase Task (CPT), a behavioral-economic task that models the relative reinforcing value of smoking under varying monetary constraint. Dependence severity was measured using the Heaviness of Smoking Index (HSI), Fagerström Test for Nicotine Dependence total scores (FTND), and FTND total scores minus items 1 and 4 (FTND 2,3,5,6 ). We also assessed associations between dependence severity and smoking motivation with nicotine levels and metabolism rate. Principal Component Analysis was used to examine the latent structure of the conventional five CPT indices; bivariate and multivariable modeling was used to test associations. Factor analysis resulted in a two-factor solution, Amplitude (demand unconstrained by price) and Persistence (price sensitivity). CPT latent factors were associated with each dependence-severity measure (ps ≤ 0.0001), with associations stronger for Amplitude than Persistence across each, especially HSI which was exclusively associated with Amplitude . Amplitude and each dependence measure were associated with nicotine intake (ps ≤ 0.0002); Persistence was not (p = .19). Demand Amplitude more than Persistence appears key to understanding individual differences in dependence severity. Regarding potential application, the results suggest a need for interventions that more effectively target demand Amplitude to make greater headway in reducing smoking in vulnerable populations. Trial Registration:clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Smokers with serious mental illness (SMI) are less responsive to cessation treatments than those without SMI. In this study, we compared smokers with and without SMI on validated measures of biological and psychosocial factors associated with tobacco use. Smokers with (n = 58) and without SMI (n = 83) who were enrolled in parallel clinical trials were compared on measures of carbon monoxide (CO) exposure, nicotine exposure, tobacco-specific nitrosamine exposure, craving, smoking motives, affect, perceived stress, environmental exposure to smoke/smokers, respiratory symptoms, tobacco-related health risk perceptions, and whether they had received recent advice to quit smoking from a health care provider. Data were collected between 2013 and 2017 in Providence, Rhode Island, USA. Samples were compared using independent-sample t-tests and chi-squared tests. Smokers with SMI had higher CO, nicotine, and tobacco-specific nitrosamine exposure levels, greater cigarette dependence, higher craving, and higher scores on eight out of eleven smoking motives (p's < 0.05). Smokers with SMI reported more severe respiratory symptoms but lower perceived health risks of tobacco (p's < 0.05). These smokers were more likely to report having received advice to quit from a medical provider in the past 6 weeks (p < 0.05). Affect, stress, and exposure to smoke/smokers did not differ across samples. Our findings advance the understanding of the elevated smoking rates of people with SMI by comparing smokers with and without SMI on validated biopsychosocial measures. There is a need for interventions that reduce craving, reduce smoking motives, and increase risk awareness among smokers with SMI., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Behavioral economic purchase tasks are used to estimate the reinforcing value of drugs by asking participants how much they would purchase across a range of increasing prices. We sought to validate such a task for e-cigarettes in experienced users of advanced generation, tank-style devices., Methods: Dual users of cigarettes and e-cigarettes (N = 54) and exclusive e-cigarette users (N = 59) attended one session during which they completed assessments including two versions of the E-cigarette Purchase Task: one that asked how many puffs of their e-cigarette they would purchase in 24 hours at varying prices and one that asked how many mLs of e-liquid they would purchase. We correlated purchase task outcomes with other measures of e-cigarette use. We also compared the tasks across dual and exclusive users., Results: Indices derived from the mLs-based task were more likely to be correlated with self-reported use rates, e-cigarette dependence, and cotinine levels than the puffs-based task. Exclusive users showed greater demand on than dual users only on the mLs version when using an F-test comparison method, while multivariate analysis of variance (MANOVA) results showed that dual users showed greater demand only on the puffs task., Conclusions: Results indicate that the mLs version had greater validity than the puffs version in terms of clinical indices. Dual users may still be on a trajectory to fully switching to e-cigarettes; thus, puffs as a measure may be more intuitive, as this measure is shared by cigarettes and e-cigarettes. For exclusive users, the unit they purchase their e-liquid in may be the most relevant unit and better capture their demand for that product., Implications: Behavioral economic purchase tasks have been widely used to understand nicotine use. We have developed two versions of a purchase task for e-cigarette use and compared the two versions in users of advanced generation e-cigarette devices. We found that the mLs version of the task better-reflected use patterns relative to a puffs version, which suggests that participants struggle to place monetary value on a unit of consumption (ie, puffs). Validated measures of e-cigarette reinforcement will be important as researchers and regulators determine which features of these products contribute to reinforcing efficacy., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: This study is part of a programmatic effort evaluating the effects of reducing nicotine content of cigarettes to minimally addictive levels., Objective: To examine whether very low-nicotine-content (VLNC) cigarettes decrease smoking rates and dependence severity among smokers with psychiatric disorders or socioeconomic disadvantage., Design, Setting, and Participants: These 3 randomized clinical trials were performed at the University of Vermont, Brown University, and Johns Hopkins University between October 2016 and September 2019. Participants received 12 weeks of exposure to study cigarettes with nicotine content ranging from levels representative of commercial cigarettes (15.8 mg nicotine/g tobacco) to less than a hypothesized addiction threshold (2.4 mg/g and 0.4 mg/g). Daily smokers from 3 at-risk populations participated: individuals with affective disorders, exemplifying smokers with mental illness; individuals with opioid use disorder, exemplifying smokers with substance use disorders; and women with high school educations or less, exemplifying smokers with socioeconomic disadvantage. Data were analyzed from September 2019 to July 2020., Interventions: Random assignment to 1 of 3 study cigarettes provided weekly at no cost for 12 weeks., Main Outcomes and Measures: The primary outcome was between-group differences in mean total cigarettes smoked daily (CPD) during week 12; secondary outcomes included CPD for study and nonstudy cigarettes and dependence severity across weeks analyzed using analysis of covariance, random coefficients growth modeling, or repeated measures analysis of variance., Results: A total of 775 participants were included (mean [SD] age, 35.59 [11.05] years; 551 [71.10%] women [owing to 1 population being exclusively women]); participants smoked a mean (SD) of 17.79 (9.18) CPD at study intake. A total of 286 participants were randomized to 0.4 mg/g, 235 participants were randomized to 2.4 mg/g, and 254 participants were randomized to 15.8 mg/g. Participants randomized to VLNC cigarettes had decreased mean [SEM] total CPD during week 12 across populations (Cohen d = 0.61; P < .001). At week 12, mean (SEM) CPD decreased to 17.96 (0.98) CPD in the 0.4 mg/g group and to 19.53 (1.07) CPD in the 2.4 mg/g group, both of which were significantly different from the 15.8 mg/g group (25.08 [1.08] CPD at week 12) but not each other (0.4 mg/g adjusted mean difference: -7.54 [95%CI, -9.51 to -5.57]; 2.4 mg/g adjusted mean difference: -5.34 [95% CI, 7.41 to -3.26]). Several secondary outcomes differed across populations randomized to VLNCs, including mean total CPD across weeks, with linear trends lower in participants receiving 0.4 mg/g (-0.28 [95%CI, -0.39 to -0.18]; P < .001) and 2.4 mg/g (-0.13 [95%CI, -0.25 to -0.01]; P < .001) doses compared with those receiving the 15.8 mg/g dose (0.30 [95% CI, 0.19 to 0.41]). Fagerström Test of Nicotine Dependence mean total scores were significantly lower in participants who received VLNCs (Cohen d = 0.12; P < .001), with those who received the 0.4 mg/g dose (mean [SD] score, 3.99 [0.06]; P < .001 vs 15.8 mg/g) or 2.4 mg/g dose (mean [SD] score, 4.07 [0.06]; P = .01 vs 15.8 mg/g) differing from those who received the 15.8 mg/g dose (mean [SD] score, 4.31 [0.06]) but not from each other., Conclusions and Relevance: These findings demonstrate that decreasing the nicotine content of cigarettes to very low levels reduced smoking rate and nicotine-dependence severity in these high-risk populations, effects that may facilitate successful cessation., Trial Registration: ClinicalTrials.gov Identifiers: NCT02232737, NCT02250664, NCT02250534.

Introduction: A nicotine-reduction policy could have major benefits for smokers with serious mental illness (SMI). However, potential unintended consequences, such as compensatory smoking, should be considered to ensure that such a policy does not negatively affect this population. The purpose of this secondary analysis was to examine the impact of smoking very low nicotine content (VLNC) cigarettes for 6 weeks on smoking topography characteristics, indicators of compensatory smoking, among smokers with SMI., Aims and Methods: After a baseline usual brand smoking phase, smokers with SMI (N = 58) were randomly assigned under double-blind conditions to receive either VLNC (0.4 mg nicotine per g tobacco) or normal nicotine content (NNC; 15.8 mg nicotine per g tobacco) research cigarettes for 6 weeks. During two study visits scheduled 6 weeks apart, participants smoked either their usual brand (baseline) or assigned study cigarettes (postrandomization) through a handheld smoking topography device. Univariate analysis of variance compared smoking topography indices with cigarette condition (VLNC vs. NNC) as the between-subjects factor with corresponding baseline topography results included as covariates., Results: At week 6, participants in the VLNC condition smoked fewer puffs per cigarette and had shorter interpuff intervals compared to participants in the NNC condition (ps < .05). There were no differences between research cigarette conditions at week 6 for cigarette volume, puff volume, puff duration, peak flow rate, or carbon monoxide boost., Conclusions: Findings are consistent with acute VLNC cigarette topography studies and indicate that a nicotine-reduction policy is unlikely to lead to compensation among smokers with SMI., Implications: Given the high smoking rates among people with SMI, understanding how a nicotine-reduction policy may affect this population is critically important. When considering the smoking topography results as a whole, smokers with SMI did not engage in compensatory smoking behavior when using VLNC cigarettes during a 6-week trial. Study findings suggest that compensatory smoking is not likely to occur among smokers with SMI if nicotine content is lowered to minimally addictive levels., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Reports in relatively healthy smokers suggest men are more sensitive than women to the subjective effects of reduced nicotine content cigarettes (RNCCs). We know of no reports examining sex differences in the relative reinforcing effects of RNCCs, an important outcome in assessing smoking's addiction potential. The aim of the present study is to address this gap by examining sex/gender differences on reinforcing effects while examining whether sex differences in subjective effects are discernible in vulnerable populations., Methods: Secondary analysis of a within-subject, double-blinded experiment examining acute effects of cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g) among 169 adult smokers with psychiatric conditions or socioeconomic disadvantage. Effects of dose, sex, and their interaction were examined on reinforcing (concurrent-choice and Cigarette Purchase Task [CPT] testing), and subjective effects (Cigarette Evaluation Questionnaire [CEQ] and craving/withdrawal ratings)., Results: Reducing nicotine content decreased the relative reinforcing effects of smoking in concurrent-choice and CPT testing (p's < .05) with no significant effects of sex nor dose × sex/gender interactions. Reducing nicotine content decreased CEQ ratings with only a single significant effect of sex (higher Psychological Reward scores among women than men, p = .02) and no significant dose × sex/gender interactions. Results on craving/withdrawal paralleled those on the CEQ., Conclusions: Reducing nicotine content decreases the addiction potential of smoking independent of sex in populations highly vulnerable to smoking and addiction, with no indication that women are less sensitive to subjective effects of RNCCs or would benefit less from a policy reducing the nicotine content of cigarettes., Implications: A policy reducing the nicotine content of cigarettes has the potential to reduce the addiction potential of smoking across men and women who are especially vulnerable to smoking, addiction, and tobacco-related adverse health impacts., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The Reinforcer Pathology Model describes how two behavioral economic processes, increased sensitivity to immediate rewards (delay discounting) and excessive reward derived from a substance (demand), both contribute to problematic patterns of substance use. In a novel application of this model, the current cross-sectional study examined how these distinct processes relate to different facets of cigarette use in adolescents., Methods: Adolescent daily cigarette smokers ages 15 to 19 (Mean age 17.7, N = 50) completed a laboratory assessment of demand using a Cigarette Purchase Task for their usual brand cigarettes and an adjusting-amount delay discounting task. Demand was conceptualized as two factors (Amplitude and Persistence) and delay discounting was calculated as Area Under the Curve (log AUC). The two factors of demand and discounting AUC were included as statistical predictors of level of cigarette dependence and average number of cigarettes smoked per day in linear regression models., Results: Amplitude of demand was marginally significant predictor (p = .06) of cigarettes smoked per day whereas neither Persistence of demand nor delay discounting significantly predicted this outcome. Both Amplitude of demand and delay discounting, but not Persistence, were associated with level of cigarette dependence. The effects of amplitude of demand and delay discounting on cigarette dependence or use did not significantly interact., Conclusions: Results of this study suggest that amplitude of cigarette demand may be a risk factor for both cigarette consumption and dependence, while discounting - a known risk factor for cigarette initiation - may relate specifically to level of dependence., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: A mandated reduction in the nicotine content of cigarettes could reduce smoking rate and prevalence. However, one concern is that smokers may compensate by increasing the intensity with which they smoke each cigarette to obtain more nicotine. This study assessed whether smokers engage in compensatory smoking by estimating the mouth-level nicotine intake of low nicotine cigarettes smoked during a clinical trial., Methods: Smokers were randomly assigned to receive cigarettes with one of five nicotine contents for 6 weeks. An additional group received a cigarette with the lowest nicotine content, but an increased tar yield. The obtained mouth-level nicotine intake from discarded cigarette butts for a subset of participants (51-70/group) was estimated using solanesol as described previously. A compensation index was calculated for each group to estimate the proportion of nicotine per cigarette recovered through changes in smoking intensity., Results: There was no significant increase in smoking intensity for any of the reduced nicotine cigarettes as measured by the compensation index (an estimated 0.4% of the nicotine lost was recovered in the lowest nicotine group; 95% confidence interval, -0.1 to 1.2). There was a significant decrease in smoking intensity for very low nicotine content cigarettes with increased tar yield., Conclusions: Reductions in nicotine content did not result in compensatory changes in how intensively participants smoked research cigarettes., Impact: Combined with data from clinical trials showing a reduction in cigarettes smoked per day, these data suggest that a reduction in nicotine content is unlikely to result in increased smoke exposure., (©2020 American Association for Cancer Research.)