Changes in Cigarette Consumption With Reduced Nicotine Content Cigarettes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage: 3 Randomized Clinical Trials.

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.

Changes in Cigarettes per Day and Biomarkers of Exposure Among US Adult Smokers in the Population Assessment of Tobacco and Health Study Waves 1 and 2 (2013-2015).

INTRODUCTION: Some studies have found some reduction in tobacco exposure and tobacco-related disease risk with decreased numbers of cigarettes smoked per day (CPD), but biomarker of exposure estimates by change in CPD are generally unavailable for the US population. METHODS: We analyzed biomarker of exposure data by smoking status from over 1100 adult exclusive daily cigarette smokers in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study who were either exclusive daily smokers or had quit tobacco use entirely at Wave 2. Wave 1 smoking categories consisted of "very light" (1-4 CPD), "light" (5-9 CPD), "moderate" (10-19 CPD), and "heavy" (20+ CPD), and Wave 2 categories were "quitters" (stopped smoking entirely), exclusive cigarette "reducers" (CPD decreased ≥ 50%), "maintainers" (CPD within 50%-150% of Wave 1 value), and "increasers" (CPD increased ≥ 50%). RESULTS: Complete quitters had significantly lower levels of TNE-2, NNAL, NNN, 2-Fluorene, HPMA, CYMA, and MHB3 at Wave 2 for all Wave 1 CPD categories, and decreases were often large. Moderate "reducers" had lower levels of NNAL and 1-Hydroxypyrene at Wave 2, and heavy "reducers" had lower levels of NNAL, 2-Fluorene, and MHB3. Light "increasers" had higher levels of TNE-2, NNAL, 2-Fluorene, CYMA, and cadmium at Wave 2, and heavy "increasers" had higher levels of NNAL and HPMA. CONCLUSIONS: Smoking "reducers" and "increasers" had changes in some biomarker of tobacco exposure levels, but reductions were much greater and more consistent for complete quitters. IMPLICATIONS: PATH longitudinal cohort study data show that some exclusive daily cigarette smokers increase or decrease CPD over time. These differences may result in moderate changes in the levels of some biomarkers such as NNAL. Even so, however, reductions in biomarker levels are much greater with complete smoking cessation.

Associations of Cigarettes Smoked Per Day with Biomarkers of Exposure Among U.S. Adult Cigarette Smokers in the Population Assessment of Tobacco and Health (PATH) Study Wave 1 (2013-2014).

BACKGROUND: The dose-response relationships between number of cigarettes smoked per day (CPD) and health outcomes, such as cancer and heart disease, are well established, but much less is known about the relationships between CPD and biomarkers of exposure. METHODS: We analyzed biomarker data by CPD from more than 2,700 adult daily cigarette smokers in Wave 1 of the Population Assessment of Tobacco and Health Study. Tobacco use categories consisted of exclusive cigarette smokers, dual cigarette and e-cigarette users, and dual cigarette and smokeless tobacco users. RESULTS: Biomarker concentrations consistently increased with CPD for each tobacco user group, although concentrations tended to level off at high smoking levels, such as those at and above 20 CPD. Dual cigarette and e-cigarette users had higher levels of some biomarkers such as Total Nicotine Equivalents-2 (P = 0.0036) than exclusive cigarette smokers, and dual cigarette and smokeless tobacco users had higher levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (P < 0.0001) and N'-nitrosonornicotine (P = 0.0236) than exclusive cigarette smokers. CONCLUSIONS: Among daily smokers, exposure to tobacco toxicants and constituents exhibits a dose-response relationship by number of cigarettes smoked, but the relationship is not necessarily linear in form. Dual users of cigarettes with either e-cigarettes or smokeless tobacco are exposed to higher levels of certain toxicants and carcinogens than exclusive cigarette smokers. IMPACT: Availability of biomarker data by CPD may aid in comparisons between cigarette smoking and use of new and potentially reduced exposure tobacco products, which may result in different levels of constituent and toxicant exposure.

The Impact of Nicotine Dose on the Reinforcing Value of Cigarettes in Adolescents.

OBJECTIVES: The FDA is considering the implementation of a national nicotine reduction policy for cigarettes, and such a policy may reduce the reinforcing efficacy of cigarettes and ultimately reduce tobacco dependence. However, it is not yet known how different levels of nicotine may affect the reinforcing efficacy of cigarettes in adolescents. We aimed to determine how reduced nicotine content may affect adolescents' demand for cigarettes using the cigarette purchase task (CPT). METHODS: Adolescent daily smokers (ages 15-19, n = 50) completed a CPT for their usual brand cigarette and for each dose of SPECTRUM research cigarettes (15.8, 5.2, 1.3, 0.4 mg nicotine/g tobacco) during four laboratory sessions. We conducted repeated measures ANOVAs to evaluate the effect of nicotine dose on five demand indices derived from the CPT. RESULTS: Tests revealed significantly higher demand for usual brand than each research cigarette dose (all p's < .01); dose did not significantly affect any measure when usual brand was excluded. CONCLUSIONS: These results demonstrate the potential utility of the CPT for comparing the reinforcing efficacy of cigarettes varying in nicotine content in adolescents, and indicate a significantly reduced reinforcing efficacy of all research cigarettes relative to usual brand.

Response to Reduced Nicotine Content in Vulnerable Populations: Effect of Menthol Status.

OBJECTIVES: In this study, we investigated potential effects of being a menthol smoker on response to reduced nicotine content (RNC) cigarettes in smokers especially vulnerable to smoking. METHOD: Participants were 169 smokers (61 menthol and 108 non-menthol smokers) with comorbid mental illness, substance use disorder, or socioeconomic disadvantage. Participants completed a double-blind study assessing addiction potential, withdrawal/craving, and compensatory smoking across 4 research cigarettes varying in nicotine content from very low levels to commercial levels (0.4, 2.4, 5.2, 15.8mg/g of tobacco). Repeated measures analysis of variance was used to examine potential moderating effects of menthol status. RESULTS: Statistically significant effects of nicotine dose were noted across measures, with higher doses producing greater economic demand and relief from withdrawal/craving. The relationships between nicotine dose and response to RNC cigarettes do not differ by menthol status. CONCLUSIONS: Results of this study suggest menthol does not have a differential impact on response to RNC cigarettes across measures of economic demand, withdrawal/craving, or smoking topography. These results suggest that any potential beneficial effects of RNC cigarettes should extend to menthol smokers including those especially vulnerable to smoking.

Modeling nicotine regulation: A review of studies in smokers with mental health conditions.

Smokers with mental health conditions (MHCs) lose approximately 15 years of life relative to non-smokers without MHCs, of which two-thirds are attributable to smoking. The Food and Drug Administration (FDA) recently announced a new regulatory strategy for tobacco that includes a reduction in the nicotine content of cigarettes sold in the US to a minimally-addictive level. This action could improve cessation rates in smokers with MHCs by reducing their dependence on nicotine. However, nicotine reduction also could have unintended negative consequences in smokers with MHCs. Thus, it is important to conduct randomized controlled trials to investigate the potential effects of nicotine reduction in smokers with MHCs. Several studies of the acute or extended effects of nicotine reduction in smokers with emotional disorders or serious mental illness have been recently completed or are underway. Studies to date indicate that when smokers with MHCs are switched, under randomized, double-blind conditions, to cigarettes with very low nicotine content, they reduce their cigarette intake, with minimal or no effects on withdrawal, psychiatric symptoms, or compensatory smoking. However, some deleterious effects of nicotine reduction on cognitive performance measures in smokers with schizophrenia have been observed, which are offset by providing concurrent nicotine replacement. We review these studies and provide suggestions for potentially increasing the effectiveness of a nicotine reduction strategy for reducing smoking in people with MHCs. The research described was conducted in the United States in 2010-2018.

Promoting smoking abstinence among patients with chronic obstructive pulmonary disease: Initial feasibility.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the U.S., with the majority of COPD deaths attributable to cigarette smoking. Despite this, individuals with COPD have a higher prevalence of smoking, poorer quit rates, and higher relapse rates compared to smokers without a COPD diagnosis. We examined the feasibility of an incentives-based intervention for producing an initial period of biochemically-verified smoking abstinence among daily smokers with COPD. Participants were randomly assigned to a Contingent (n = 13) or Noncontingent (n = 16) incentives condition and visited the clinic for 14 consecutive days. Contingent participants earned vouchers with monetary value contingent on breath carbon monoxide (CO) levels during Study Days 1-5 and urinary cotinine during Days 6-14. Voucher earnings began at $9.00 and increased by $1.50 with each subsequent negative sample for maximum possible of $362.50. Noncontingent participants received vouchers of comparable value independent of smoking status. Differences between conditions varied across study days for daily smoking abstinence (X2 = 45.27, p < 0.0001), CO (F(13, 280) = 1.95, p = 0.025), and cotinine (F(13, 279) = 2.20, p = 0.010), with generally higher rates of abstinence and lower CO and cotinine levels observed in the Contingent vs. Noncontingent conditions. Results from this randomized pilot study support the potential efficacy of an incentives-based intervention for reducing cigarette smoking among individuals with COPD. Further research efforts should seek to promote and evaluate longer-term abstinence and associated changes in respiratory function.

Posttraumatic stress disorder and tobacco use: A systematic review and meta-analysis.

Posttraumatic stress disorder (PTSD) and tobacco use are prevalent conditions that co-occur at striking rates in the US. Previous reviews examined prevalence and factors associated with cigarette smoking among individuals with PTSD but have not been summarized since 2007. Moreover, none explored rates and factors associated with the use of other tobacco products. This study aimed to systematically review the most recent literature examining the comorbidity of PTSD and tobacco use to provide prevalence rates, as well as summarize the literature exploring other factors associated with tobacco use among individuals with PTSD. Studies were identified using a systematic search of keywords related to tobacco use and PTSD within the following databases: PubMed, PsycINFO, Web of Knowledge, CINAHL, PsycARTICLES, and Cochrane Clinical Trials Library. The studies included in this review (N = 66) showed that the prevalence of current use of tobacco products in individuals with PTSD was 24.0% and the rate of PTSD among users of tobacco products was 20.2%. Additionally, results demonstrated that individuals with PTSD present with high levels of nicotine dependence and heavy use of tobacco products, as well as underscore the importance of negative emotional states as a contributing factor to tobacco use among individuals with PTSD. It is imperative that future studies continue monitoring tobacco use among individuals with PTSD while also assessing factors identified as having a prominent role in tobacco use among individuals with PTSD. These findings also demonstrate the need for more innovative approaches to reduce the pervasive tobacco use among individuals with PTSD.

Response to reduced nicotine content cigarettes among smokers differing in tobacco dependence severity.

This study examines whether tobacco dependence severity moderates the acute effects of reducing nicotine content in cigarettes on the addiction potential of smoking, craving/withdrawal, or smoking topography. Participants (N = 169) were daily smokers with mild, moderate, or high tobacco-dependence severity using the Heaviness of Smoking Index. Following brief abstinence, participants smoked research cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg nicotine/g tobacco) in a within-subject design. Results were analyzed using repeated measures analysis of co-variance. No main effects of dependence severity or interactions with nicotine dose were noted in relative reinforcing effects in concurrent choice testing or subjective effects on the modified Cigarette Evaluation Questionnaire. Demand for smoking in the Cigarette Purchase Task was greater among more dependent smokers, but reducing nicotine content decreased demand independent of dependence severity. Dependence severity did not significantly alter response to reduced nicotine content cigarettes on the Minnesota Tobacco Withdrawal Scale nor Questionnaire of Smoking Urges-brief (QSU) Factor-2 scale; dependence severity and dose interacted significantly on the QSU-brief Factor-1 scale, with reductions dependent on dose among highly but not mildly or moderately dependent smokers. Dependence severity and dose interacted significantly on only one of six measures of smoking topography (i.e., maximum flow rate), which increased as dose increased among mildly and moderately but not highly dependent smokers. These results suggest that dependence severity has no moderating influence on the ability of reduced nicotine content cigarettes to lower the addiction potential of smoking, and minimal effects on relief from craving/withdrawal or smoking topography.

Contingency management for college student smokers: The role of drinking as a moderator and mediator of smoking abstinence during treatment.

INTRODUCTION: Contingency management (CM) is effective for promoting smoking abstinence; however, moderators and mediators of CM treatment efficacy in young adult populations are under-explored. We leveraged fine-grained data from a large randomized controlled trial: 1) to determine whether early attainment of sustained abstinence mediated the effect of treatment on abstinence; 2) to test whether heavy drinking moderated the effect of treatment on abstinence; and 3) to test a serial mediation model of the effects of drinking during early treatment on sustained smoking abstinence. METHODS: College student smokers (N=110) were randomized to receive either CM treatment or noncontingent reinforcement (NR) over a 21-day treatment period. All participants received $5 for providing twice-daily breath carbon monoxide (CO) samples. In CM, additional money was provided for samples that indicated smoking reduction (Initial Phase; first 7days), and for samples ≤5ppm (Abstinence Phase; following 14days). RESULTS: CM treatment led to greater sustained abstinence relative to NR. Longer sustained abstinence in the Initial Phase partially mediated the effect of treatment on sustained abstinence in the Abstinence Phase. Heavier pretreatment drinkers had shorter periods of sustained abstinence in the Abstinence Phase; this effect was greater in CM. A serial mediation model determined that increased drinking during the Initial Phase led to decreased sustained abstinence, which then led to decreased sustained abstinence in the Abstinence Phase. CONCLUSIONS: These data provide a greater understanding of how heavy drinking and early sustained abstinence may affect success during treatment in young adults undergoing contingency management treatment for smoking.

Self-perceived Mental Health and Population-level Tobacco Use Disparities.

OBJECTIVES: Poor mental health is associated with increased cigarette smoking, yet whether this extends to alternative tobacco product use remains unknown. METHODS: Wave 1 data from the Population Assessment of Tobacco and Health study assessed relationships between self-perceived mental health (SPMH) and prevalence of and motives for tobacco use among US adults (N = 32,320). RESULTS: Fair/poor SPMH, as compared to good/excellent SPMH, was associated with increased current cigarette (AOR = 2.91, 95% CI = 2.64, 3.20), e-cigarette (AOR = 1.35, 95% CI = 1.20, 1.53), cigarillo (AOR = 1.38, 95% CI = 1.22, 1.56), filtered cigar (AOR = 1.43, 95% CI = 1.21, 1.70), and smokeless tobacco (AOR = 1.17, 95% CI = 1.01, 1.36), but not traditional cigar use (AOR = 1.04, 95% CI = 0.90, 1.20). Whereas most motives for tobacco use were similar across SPMH rating, those with fair/poor SPMH, as compared to good/excellent SPMH, were more likely to report using traditional cigars due to affordability (AOR = 1.56, 95% CI = 1.23, 1.98) and e-cigarettes (AOR = 1.43, 95% CI = 1.15, 1.79) and smokeless tobacco (AOR = 1.84, 95% CI = 1.19, 2.83) due to appealing advertising. CONCLUSIONS: Although individuals with poor SPMH are more likely to use alternative tobacco products than those with better SPMH, most motives for use are strikingly similar. These findings highlight the importance of continual monitoring of tobacco use trends among vulnerable populations.

Addiction Potential of Cigarettes With Reduced Nicotine Content in Populations With Psychiatric Disorders and Other Vulnerabilities to Tobacco Addiction.

Importance: A national policy is under consideration to reduce the nicotine content of cigarettes to lower nicotine addiction potential in the United States. Objective: To examine how smokers with psychiatric disorders and other vulnerabilities to tobacco addiction respond to cigarettes with reduced nicotine content. Design, Setting, and Participants: A multisite, double-blind, within-participant assessment of acute response to research cigarettes with nicotine content ranging from levels below a hypothesized addiction threshold to those representative of commercial cigarettes (0.4, 2.3, 5.2, and 15.8 mg/g of tobacco) at 3 academic sites included 169 daily smokers from the following 3 vulnerable populations: individuals with affective disorders (n = 56) or opioid dependence (n = 60) and socioeconomically disadvantaged women (n = 53). Data were collected from March 23, 2015, through April 25, 2016. Interventions: After a brief smoking abstinence, participants were exposed to the cigarettes with varying nicotine doses across fourteen 2- to 4-hour outpatient sessions. Main Outcomes and Measures: Addiction potential of the cigarettes was assessed using concurrent choice testing, the Cigarette Purchase Task (CPT), and validated measures of subjective effects, such as the Minnesota Nicotine Withdrawal Scale. Results: Among the 169 daily smokers included in the analysis (120 women [71.0%] and 49 men [29.0%]; mean [SD] age, 35.6 [11.4] years), reducing the nicotine content of cigarettes decreased the relative reinforcing effects of smoking in all 3 populations. Across populations, the 0.4-mg/g dose was chosen significantly less than the 15.8-mg/g dose in concurrent choice testing (mean [SEM] 30% [0.04%] vs 70% [0.04%]; Cohen d = 0.40; P < .001) and generated lower demand in the CPT (α = .027 [95% CI, 0.023-0.031] vs α = .019 [95% CI, 0.016-0.022]; Cohen d = 1.17; P < .001). Preference for higher over lower nicotine content cigarettes could be reversed by increasing the response cost necessary to obtain the higher dose (mean [SEM], 61% [0.02%] vs 39% [0.02%]; Cohen d = 0.40; P < .001). All doses reduced Minnesota Nicotine Withdrawal Scale total scores (range of mean decreases, 0.10-0.50; Cohen d range, 0.21-1.05; P < .001 for all), although duration of withdrawal symptoms was greater at higher doses (η2 = 0.008; dose-by-time interaction, P = .002). Conclusions and Relevance: Reducing the nicotine content of cigarettes may decrease their addiction potential in populations that are highly vulnerable to tobacco addiction. Smokers with psychiatric conditions and socioeconomic disadvantage are more addicted and less likely to quit and experience greater adverse health impacts. Policies to reduce these disparities are needed; reducing the nicotine content in cigarettes should be a policy focus.

Electronic Cigarette Expectancies in Smokers with Psychological Distress.

OBJECTIVES: Very few studies have evaluated perceptions of electronic nicotine delivery systems (ENDS) among smokers with mental illness. This study assessed expectancies about the effects of smoking combustible cigarettes or using ENDS among current smokers with and without severe psychological distress (SPD). METHODS: We used a crowdsourcing system to survey 268 smokers on their expectancies for the effects of combustible cigarettes and ENDS. Positive expectancies assessed included negative affect reduction, stimulation, positive social effects and weight control, and negative expectancies included negative physical effects, negative psychosocial effects and future health concerns. RESULTS: Smokers with SPD had higher positive expectancies for weight control and social effects of both products compared to those without such distress, and higher expectancies for stimulation from combustible cigarettes compared to ENDS. All participants had significantly lower negative expectancies for ENDS compared to combustible cigarettes, with no significant differences between the groups. CONCLUSIONS: Smokers with SPD may be more vulnerable toward ENDS use, as they are for combustible cigarette use, due to greater positive expectancies of the products. Challenging positive expectancies may increase the efficacy of tobacco control efforts in this vulnerable population.

Response to varying the nicotine content of cigarettes in vulnerable populations: an initial experimental examination of acute effects.

RATIONALE: The purpose of this study was to begin researching the effects of very low nicotine content cigarettes in smokers especially vulnerable to dependence to assess their potential as a less dependence-producing alternative to current commercial cigarettes. METHODS: Participants were 26 adult, daily cigarette smokers from one of three populations: economically disadvantaged women of reproductive age (n = 9), opioid-dependent individuals (n = 11), and individuals with affective disorders (n = 6). Participants completed fourteen 2-4-h experimental sessions in a within-subjects research design. Sessions were conducted following brief smoking abstinence. Four research cigarettes varying in nicotine content (0.4, 2.4, 5.2, and 15.8 mg/g) were studied under double-blind conditions, assessing smoking topography, subjective effects, and relative reinforcing effects of varying doses in concurrent choice tests. Results were collapsed across vulnerable populations and analyzed using repeated measures ANOVA. RESULTS: No significant differences between doses were discernible in smoking topography. All doses were equi-effective at reducing nicotine withdrawal. Ratings of satisfaction from smoking were lower at the 0.4 compared to 15.8 mg/g dose. Participants preferred the 15.8 mg/g dose over the 0.4 and 2.4 but not the 5.2 mg/g doses in concurrent choice testing; no differences between the two lowest doses were noted. CONCLUSIONS: All cigarettes effectively reduced nicotine withdrawal with no differences in smoking topography, suggesting minimal compensatory smoking. Dependence potential was lowest at the 0.4 mg/g dose. These initial results are promising regarding the feasibility of lowering nicotine content in cigarettes to very low levels in vulnerable populations without untoward effects.

Smoking Topography Characteristics of Very Low Nicotine Content Cigarettes, With and Without Nicotine Replacement, in Smokers With Schizophrenia and Controls.

INTRODUCTION: Reducing the nicotine content of cigarettes to a minimally addictive level has been proposed as a regulatory strategy for reducing tobacco dependence. However, smokers with schizophrenia (SS) may be prone to changing their smoking topography in efforts to compensate for the reduction in nicotine content. The aims of this study were to compare smoking topography characteristics of usual-brand and very low nicotine content (VLNC) cigarettes in SS and control smokers without psychiatric illness (CS), and to determine whether nicotine replacement reversed any changes in topography produced by VLNC cigarettes. METHODS: Using a within-subjects, counter-balanced design, SS (n = 27) and CS (n = 23) smoked usual brand cigarettes, VLNC cigarettes while wearing placebo patches (VLNC + PLA), or VLNC cigarettes while wearing transdermal nicotine patches totaling 42mg (VLNC + NIC) during 5-hour ad libitum smoking sessions. Cigarettes were smoked through topography measurement devices. RESULTS: Across conditions, SS smoked more puffs per session and per cigarette, had higher cigarette volumes, and had shorter inter-puff intervals than CS (Ps < .01). During VLNC cigarette sessions, puff duration increased and time between puffs decreased, but participants smoked fewer puffs, resulting in a net decrease in cigarette and total session volume (Ps < .001). There were no significant interactions between group and condition. CONCLUSIONS: These findings indicate that acute use of VLNC cigarettes does not increase intensity of smoking in SS, and support the feasibility of a nicotine reduction policy. IMPLICATIONS: Reducing the nicotine in cigarettes to a minimally addictive level has been proposed as a means of reducing tobacco dependence. However, smokers, particularly those with schizophrenia (SS) may alter their puffing in an attempt to extract more nicotine from VLNC cigarettes. This study compared smoking topography of usual brand versus VLNC cigarettes, combined with placebo or transdermal nicotine patches, in SS and controls. Although some changes in topography were indicative of compensatory smoking, total puffs and total cigarette volume were reduced with VLNC cigarettes, indicating that acute VLNC cigarette use does not increase smoking in SS.

Financial incentives to promote extended smoking abstinence in opioid-maintained patients: a randomized trial.

BACKGROUND AND AIMS: Prior studies by our group demonstrated the efficacy of a brief but intensive behavioral intervention for producing initial smoking abstinence among opioid-dependent patients. In the present study, our aim was to promote longer-duration abstinence in this population. Following an initial 2-week incentive intervention for smoking abstinence, we examined whether a 10-week maintenance arm involving continuation of contingent reinforcement will produce greater smoking abstinence than a similar duration of noncontingent reinforcement. DESIGN: Randomized, 12-week, parallel-group study. SETTING: Out-patient research clinic in Burlington, Vermont, USA. PARTICIPANTS: Opioid-maintained smokers (n = 88) who provided breath carbon monoxide and urinary cotinine specimens and received contingent reinforcement for smoking abstinence during weeks 1-2 (phase 1), with 63 randomized on day 14 to an extended contingent (EC; n = 31) or extended noncontingent (EN; n = 32) experimental condition for weeks 3-12 (phase 2). INTERVENTION AND CONTROL: The EC condition consisted of voucher values that escalated across consecutive negative samples until they reached $30, after which they remained at $30 per negative sample. A positive or a missing sample resulted in no vouchers for that day and reset the value of the next negative same to $9. Two consecutive negatives returned the schedule to the pre-reset value. The EN control condition consisted of vouchers delivered for providing scheduled samples, but independent of smoking status. MEASUREMENTS: The primary outcome was percentage of biochemically abstinent samples during phase 2. Secondary measures included abstinence status at final study visit, complete abstinence, participants' longest duration of continuous abstinence, cotinine and carbon monoxide (CO) levels and self-reported cigarettes per day. FINDINGS: EC participants achieved greater smoking abstinence during phase 2 than EN participants [46.7 versus 23.5% negative samples, respectively; odds ratio (OR) = 2.98, 95% confidence interval (CI) = 1.16-7.65, χ(2) 1  (=)  5.0, P = 0.02]. When longest duration of continuous abstinence was compared between experimental groups, EC participants achieved twice the mean duration of continuous abstinence compared with EN participants (3.31 versus 1.68 weeks; t61  = 1.83, P = 0.07). An effect of experimental condition was also seen on mean cotinine levels (42.5 versus 210.6 ng/ml, respectively; F1,61 =5.9, P = 0.02). CONCLUSIONS: Among opioid-maintained smokers receiving an initial period of daily contingent incentives, a contingent reinforcement intervention appears to be more effective at extending smoking abstinence than noncontingent reinforcement over 10 weeks.

Behavioral Economic Laboratory Research in Tobacco Regulatory Science.

OBJECTIVES: Research that can provide a scientific foundation for the United States Food and Drug Administration (FDA) tobacco policy decisions is needed to inform tobacco regulatory policy. One factor that affects the impact of a tobacco product on public health is its intensity of use, which is determined, in part, by its abuse liability or reinforcing efficacy. Behavioral economic tasks have considerable utility for assessing the reinforcing efficacy of current and emerging tobacco products. METHODS: This paper provides a narrative review of several behavioral economic laboratory tasks and identifies important applications to tobacco regulatory science. RESULTS: Behavioral economic laboratory assessments, including operant self-administration, choice tasks and purchase tasks, can be used generate behavioral economic data on the effect of price and other constraints on tobacco product consumption. These tasks could provide an expedited simulation of the effects of various tobacco control policies across populations of interest to the FDA. CONCLUSIONS: Tobacco regulatory research questions that can be addressed with behavioral economic tasks include assessments of the impact of product characteristics on product demand, assessments of the abuse liability of novel and potential modified risk tobacco products (MRTPs), and assessments of the impact of conventional and novel products in vulnerable populations.

Smoking cessation and reduction in people with chronic mental illness.

The high prevalence of cigarette smoking and tobacco related morbidity and mortality in people with chronic mental illness is well documented. This review summarizes results from studies of smoking cessation treatments in people with schizophrenia, depression, anxiety disorders, and post-traumatic stress disorder. It also summarizes experimental studies aimed at identifying biopsychosocial mechanisms that underlie the high smoking rates seen in people with these disorders. Research indicates that smokers with chronic mental illness can quit with standard cessation approaches with minimal effects on psychiatric symptoms. Although some studies have noted high relapse rates, longer maintenance on pharmacotherapy reduces rates of relapse without untoward effects on psychiatric symptoms. Similar biopsychosocial mechanisms are thought to be involved in the initiation and persistence of smoking in patients with different disorders. An appreciation of these common factors may aid the development of novel tobacco treatments for people with chronic mental illness. Novel nicotine and tobacco products such as electronic cigarettes and very low nicotine content cigarettes may also be used to improve smoking cessation rates in people with chronic mental illness.

Predicted Impact of Nicotine Reduction on Smokers with Affective Disorders.

OBJECTIVES: In 2009 the FDA acquired the authority to reduce the nicotine content in cigarettes if appropriate for public health, prompting research to evaluate the implications of this policy scientifically. Studies in non-psychiatric populations show that reducing the nicotine content of cigarettes to non-addictive levels reduces smoking rates and nicotine dependence. However, few studies have examined this hypothesis in vulnerable populations. METHODS: In this narrative review we examined the extant literature on the effects of nicotine reduction or cessation on symptoms of withdrawal, as well as psychiatric symptoms, among those with affective disorders. RESULTS: Following initial withdrawal from nicotine, smokers with affective disorders experience more severe mood disruption than smokers without these disorders. Use of very low nicotine content (VLNC) cigarettes during abstinence may help mitigate the mood-disrupting effects of initial abstinence. Once the initial effects of nicotine withdrawal on mood have passed, longer-term abstinence is associated with psychiatric improvement rather than worsening. CONCLUSIONS: These findings suggest that if a national nicotine reduction policy were to be implemented, smokers with affective disorders would need additional support to overcome initial withdrawal but that long-term outcomes would likely be positive.

A literature review on prevalence of gender differences and intersections with other vulnerabilities to tobacco use in the United States, 2004-2014.

This report describes results from a systematic literature review examining gender differences in U.S. prevalence rates of current use of tobacco and nicotine delivery products and how they intersect with other vulnerabilities to tobacco use. We searched PubMed on gender differences in tobacco use across the years 2004-2014. For inclusion, reports had to be in English, in a peer-reviewed journal or federal government report, report prevalence rates for current use of a tobacco product in males and females, and use a U.S. nationally representative sample. Prevalence rates were generally higher in males than in females across all products. This pattern remained stable despite changes over time in overall prevalence rates. Gender differences generally were robust when intersecting with other vulnerabilities, although decreases in the magnitude of gender differences were noted among younger and older users, and among educational levels and race/ethnic groups associated with the highest or lowest prevalence rates. Overall, these results document a pervasive association of gender with vulnerability to tobacco use that acts additively with other vulnerabilities. These vulnerabilities should be considered whenever formulating tobacco control and regulatory policies.