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Cannabis misuse accounts for nearly all of the substance abuse treatment admissions among youth in the United States. Most youth do not experience sustained benefit from existing psychosocial treatments; however, medication development research for treating adolescent cannabis misuse is almost nonexistent. We conducted a double-blind, placebo-controlled, pilot study to test the potential efficacy of topiramate plus motivational enhancement therapy (MET) for treating cannabis use among adolescents. Sixty-six heavy cannabis users, ages 15 to 24 years, were randomized to one of two 6-week treatment conditions: topiramate plus MET or placebo plus MET. Topiramate was titrated over 4 weeks then stabilized at 200 mg/day for 2 weeks. MET was delivered biweekly for a total of three sessions. Only 48 percent of youths randomized to topiramate completed the 6-week trial (n = 19), compared with 77 percent of youths in the placebo condition (n = 20). Adverse medication side effects were the most common reason for withdrawal among participants in the topiramate group. Latent growth models showed that topiramate was superior to placebo for reducing the number of grams smoked per use day, but it did not improve abstinence rates. The same pattern of results was found when values for missing outcomes were imputed. We show that topiramate combined with MET demonstrated efficacy for reducing how much cannabis adolescents smoked when they used but did not affect abstinence rates. The magnitude of this effect was modest, however, and topiramate was poorly tolerated by youths, which calls into question the clinical importance of these findings. [ABSTRACT FROM AUTHOR]

Objectives: Behavioral economic purchase tasks, which estimate demand for drugs, have been developed for cigarettes and are widely used. However, a validated purchase task does not yet exist for e-cigarettes. The aim of this project was to identify the relevant units for an e-cigarette purchase task (E-CPT). Methods: We conducted focus groups (N = 28 participants in 7 groups, 2-7 participants per group) consisting of current e-cigarette users. Participants discussed their daily use patterns, completed a preliminary E-CPT that asked how many puffs of their e-cigarette they would consume per day at escalating prices, and discussed the extent to which the task accurately reflected their real-world behavior. Groups were recorded and transcribed; analysis focused on statements related to daily consumption and the E-CPT. Results: Participants were unlikely to quantify their daily use in terms of puffs, and perceptions about the appropriate unit for an E-CPT varied across device type. Users of first-generation devices (eg, cig-a-likes) reported that the relevant unit was the individual device/cartridge; however, participants who purchased nicotine liquid for their device emphasized that e-liquid volume in milliliters would better reflect their use. Conclusions: Multiple versions of the E-CPT may be necessary to provide valid measures of e-cigarette demand. [ABSTRACT FROM AUTHOR]

Background: The FDA recently acquired regulatory authority over tobacco products, leading to renewed interest in whether reducing the nicotine content of cigarettes would reduce tobacco dependence in the United States. Given the association between depressive symptoms and cigarette smoking, it is important to consider whether smokers with elevated depressive symptoms experience unique benefits or negative consequences of nicotine reduction.Methods: In this secondary analysis of a randomized clinical trial that examined the effects of cigarettes varying in nicotine content over a 6-week period in non-treatment-seeking smokers, we used linear regression to examine whether baseline depressive symptom severity (scores on the Center for Epidemiologic Studies Depression Scale [CES-D]) moderated the effects of reduced-nicotine content (RNC) cigarettes, relative to normal-nicotine content (NNC) cigarettes, on smoking rates, depressive symptom severity, and related subjective and physiological measures.Results: Of the 717 participants included in this analysis, 109 (15.2%) had CES-D scores ≥ 16, indicative of possible clinical depression. Relative to NNC cigarettes, RNC cigarettes reduced smoking rates, nicotine dependence, and cigarette craving, and these effects were not significantly moderated by baseline CES-D score. A significant interaction between baseline CES-D score and cigarette condition on week 6 CES-D score was observed (p < .05); among those with CES-D scores ≥ 16 at baseline, those assigned to RNC cigarettes had lower week 6 CES-D scores than those assigned to NNC cigarettes. Among those in the lowest nicotine content conditions, biochemically confirmed compliance with the RNC cigarettes was associated with an increase in CES-D score for those with baseline CES-D scores < 16 and no change in CES-D score for those with baseline CES-D scores ≥ 16.Conclusions: These findings provide initial evidence that a reduced-nicotine standard for cigarettes may reduce smoking, without worsening depressive symptoms, among smokers with elevated depressive symptoms.Implications: This secondary analysis of a recent clinical trial examined whether depressive symptom severity moderated the effects of reduced-nicotine cigarettes on smoking and depressive symptoms. Results indicate that, regardless of baseline depressive symptoms, participants randomized to reduced-nicotine cigarettes had lower smoking rates, nicotine intake, nicotine dependence, and craving at week 6 post-randomization than those assigned to normal-nicotine cigarettes. In participants with higher baseline depressive symptoms, those assigned to reduced-nicotine cigarettes had lower week 6 depressive symptoms than those assigned to normal-nicotine cigarettes. These results suggest that a nicotine reduction policy could have beneficial effects for smokers, regardless of depressive symptom severity. [ABSTRACT FROM AUTHOR]

Background and Aims Clinical trials on the impact and safety of reduced nicotine content cigarettes (RNCs) are ongoing, and an important methodological concern is participant compliance with smoking only RNCs. Our aims were to measure non-compliance biochemically with urine cotinine (COT) and total nicotine equivalents (TNEs), compare with self-reported non-compliance and identify associated covariates. Design Secondary analysis of a double-blind, parallel, randomized clinical trial. Setting Research centers from the United States, enrolling participants from June 2013 to July 2014. Participants Volunteer sample of 242 participants (55% Caucasian), average age of 41.2 years, smoking at least five cigarettes per day (CPD). Intervention Smoking very low nicotine cigarettes (VLNCs; 0.4 mg nicotine/g tobacco) for 6 weeks. Measurements The primary outcome was biochemically verified non-compliance, measured as thresholds of COT/CPD and TNE/CPD ratios, considering changes in nicotine content from conventional levels to VLNCs, and as an absolute threshold of week 6 TNEs. Self-reported non-compliance was measured via daily phone calls. Key predictors included age, sex, race, menthol preference, nicotine metabolite ratio, time to first cigarette, dependence, CPD, TNEs, tar level and cigarette evaluation. Findings Estimates of non-compliance with smoking the VLNCs exclusively include: the biochemical ratios (both 78%), the week 6 TNE threshold (76%) and self-report (39%). Of the key covariates, age, dependence and cigarette evaluations of satisfaction were significant; for age, younger participants more likely to be non-compliant [ P = 0.01; odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.96-0.99]. Dependence was associated significantly with self-reported non-compliance ( P = 0.01; OR = 1.28, 95% CI = 1.06-1.55). Cigarette evaluations of satisfaction were associated significantly with non-compliance ( P = 0.001; OR = 0.71, 95% CI = 0.61-0.82). Conclusions Among smokers volunteering to smoke only very low nicotine cigarettes for 6 weeks, non-compliance was common and biochemical assessments detected more cases of non-compliance than self-report. Despite high levels of non-compliance, smokers reduced their intake of nicotine by an average of 60%. [ABSTRACT FROM AUTHOR]

Serious mental illness (SMI) is associated with disproportionately high rates of cigarette smoking. The identification of factors that contribute to persistent smoking in people with SMI may lead to the development and adoption of tobacco control policies and treatment approaches that help these smokers quit. This commentary examines factors underlying smoking persistence in people with SMI from the perspective of behavioral economics, a discipline that applies economic principles to understanding drug abuse and dependence. Studies, conducted in the Northeastern US within the past 30years, that compare the reinforcing effects of nicotine and the costs of smoking in smokers with and without schizophrenia and depression are discussed, and interventions that may reduce the reinforcing efficacy of nicotine and increase the costs of smoking in people with SMI are described. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: A cigarette purchase task (CPT) is a behavioral economic measure of the reinforcing value of smoking in monetary terms (ie, cigarette demand). This study investigated whether cigarette demand predicted response to contingent monetary rewards for abstinence among individuals with substance use disorders. It also sought to replicate evidence for greater price sensitivity at whole-dollar pack price transitions (ie, left-digit effects).Methods: Participants (N = 338) were individuals in residential substance use disorder treatment who participated in a randomized controlled trial that compared contingent vouchers to noncontingent vouchers for smoking abstinence. Baseline demand indices were used to predict number of abstinent days during the 14-day voucher period (after the reduction lead-in) and at 1 and 3 months afterward.Results: Demand indices correlated with measures of smoking and nicotine dependence. As measured by elasticity, intensity and O max, higher demand significantly predicted fewer abstinent exhaled carbon monoxide readings during voucher period for individuals in the noncontingent vouchers condition. Breakpoint exhibited a trend-level association with abstinent exhaled carbon monoxide readings. Demand indices did not predict abstinence in the contingent vouchers group, and did not predict abstinence at 1- and 3-month follow-ups. Left-digit price transitions were associated with significantly greater reductions in consumption.Conclusions: The association of cigarette demand with smoking behavior only in the group for whom abstinence was not incentivized indicates that CPT assesses the value of smoking more than the value of money per se and that vouchers counteract the effects of the intrinsic reinforcing value of cigarettes. Results provide initial short-term evidence of predictive validity for the CPT indices.Implications: This study provides the first evidence of the validity of the CPT for predicting early response to brief advice for smoking cessation plus nicotine replacement in smokers with substance dependence. However, demand for cigarettes did not predict voucher-based treatment response, indicating that incentives serve as a powerful motivator not to smoke that acts in opposition to the intrinsic reinforcing value of cigarettes and that the indices reflect the value of smoking more than the value of money per se. [ABSTRACT FROM AUTHOR]

Introduction: The current study examined whether the presence of the G allele of the A118G polymorphism of the OPRM1 gene (rs1799971) and the long allele of exon 3 VNTR polymorphism of the DRD4 gene moderate the effect of alcohol administration on urge to smoke. These polymorphisms have been associated with greater alcohol induced-urge to drink. Urge to drink and alcohol consumption increase urge to smoke. Therefore, these polymorphisms may also sensitize urge to smoke after alcohol consumption.Methods: Individuals smoking 10-30 cigarettes per day and reporting heavy drinking were recruited from the community. Caucasians (n = 62), 57.3% male, mean age 39.2, took part in a three-session, within-subjects, repeated-measures design study. Participants were administered a placebo, 0.4 g/kg, or 0.8 g/kg dose of alcohol. A118G genotype, exon 3 VNTR genotype, and urge to smoke (baseline and three times after receiving alcohol) were assessed.Results: G allele carriers showed greater urge to smoke across all assessments. Additionally, a significant interaction indicated that G carriers, compared to homozygotes (AA), evinced a significantly greater increase in urge to smoke after high dose alcohol relative to placebo. The interaction between condition, DRD4 polymorphism, and time was not significant.Conclusions: Presence of G allele of the A118G polymorphism of the OPRM1 gene may lead to greater increases in urge to smoke after a high dose of alcohol. Pharmacotherapies targeted to opiate receptors (eg, naltrexone) may be especially helpful in aiding smoking cessation among G carriers who are heavy drinkers. [ABSTRACT FROM AUTHOR]

Introduction: Lapses after smoking cessation often occur in the context of alcohol use, possibly because alcohol increases urge to smoke. Poor working memory, or alcohol-induced decrements in working memory, may influence this relationship by making it more difficult for an individual to resist smoking in the face of smoking urges. Methods: Participants (n = 41) completed measures of working memory and urge to smoke before and after alcohol administration (placebo, 0.4 g/kg, and 0.8 g/kg, within subjects) and then participated in a laboratory analogue task in which smoking abstinence was monetarily incentivized. Results: Working memory moderated the relationship between smoking urge and latency to smoke: for those with relatively poorer working memory, urge to smoke was more strongly and negatively associated with latency to smoke (i.e., higher urges were associated with shorter latency). Conclusions: Those with weak working memory may need additional forms of treatment to help them withstand smoking urges. [ABSTRACT FROM AUTHOR]

Introduction: Beneficial effects of nicotine on cognitive functioning may contribute to the markedly high rates of smoking among people with schizophrenia. A reduction in the nicotine content of cigarettes to non-addictive levels is being considered as a regulatory strategy for reducing tobacco dependence in the United States. We examined whether switching to very low nicotine content (VLNC) cigarettes impairs cognitive functioning in smokers with and without schizophrenia, andwhether nicotine replacement reverses these effects. Methods: Smokers with schizophrenia (SS, n = 29) and control smokers matched on smoking rate but without psychiatric illness (CS, n = 28) smoked usual-brand cigarettes, VLNC cigarettes while wearing 2 placebo patches (PLA), or VLNC cigarettes while wearing 2 nicotine patches totaling 42 mg (NIC) for 5 hr, and then completed computerized assessments of visual sustained attention, motor speed, visual working memory, processing speed, inhibitory control, and response variability. Results: Across conditions, SS were slower than CS in tasks of motor speed and visual working memory, and had poorer target detectability on a visual sustained attention task. Across groups, functioning in domains of visual sustained attention, inhibitory control, processing speed, and response variability was impaired in the VLNC + PLA condition relative to the usual-brand and VLNC + NIC conditions. Conclusions: Dramatically reducing the nicotine content of cigarettes may impair cognitive functioning in heavy smokers with and without schizophrenia, but the use of nicotine replacement while smoking VLNC cigarettes may preserve cognitive functioning in these smokers. [ABSTRACT FROM AUTHOR]

Introduction: Schizophrenia is associated with a high prevalence of cigarette smoking. The aims of this study were to compare smokers with schizophrenia (SS) and control smokers without psychiatric illness (CS) on (a) cigarette craving and nicotine withdrawal symptom severity during a 72-hr smoking abstinence period; (b) nicotine reinforcement, before and after abstinence; and (c) latency to smoking lapse following abstinence. We also explored mediators of smoking lapse in SS and CS. Methods: SS (n = 28) and CS (n = 27) underwent a nicotine versus denicotinized cigarette puff choice task before and after a 72-hr period of smoking abstinence that was experimentally controlled by providing cash reinforcement contingent on biochemical verification of abstinence. Twenty-four hours after the second choice task, participants could receive a low-value reinforcer if they had continued to abstain since the previous day. Those who remained abstinent were recontacted a week later to determine time of their smoking lapse. Results: SS reported more severe cigarette craving and nicotine withdrawal symptoms throughout the 72-hr abstinence period, had greater nicotine preference after abstinence, and lapsed back to smoking significantly sooner than CS. The relationship between group and smoking lapse latency was mediated by baseline depression and nicotine withdrawal symptom severity but not by effects of abstinence on craving or nicotine reinforcement. Conclusions: Overall, these results indicate that negative affect is a key contributor to poor smoking cessation outcomes among those with schizophrenia. [ABSTRACT FROM PUBLISHER]

People with HIV (PWH) experience higher rates of cardiovascular events (CVEs) compared with the general population. A substantial body of evidence supports that select biomarkers of inflammation (soluble CD14 [sCD14], soluble CD163 [sCD163], highly sensitive C-reactive protein [hs-CRP], interleukin-6 [IL-6]) and coagulation (D-dimer) are elevated in PWH and related to increased rates of CVEs. Our previous work showed that smoking compared with nonsmoking was associated with significantly elevated sCD14, a biomarker of monocyte activation. We aimed to explore the effect of electronic cigarette (EC) provision on inflammatory biomarkers in PWH who smoked daily and then switched to an EC. Nineteen PWH were enrolled in a pilot study in which an EC and e-liquid were provided weekly for 8 weeks. Blood specimens for inflammatory biomarker analysis were obtained at baseline (BL) and at week 8. Biomarker levels were high at BL and did not differ significantly at week 8. There were small nonsignificant reductions in sCD163 and CRP levels. Non-significant increases in IL-6, D-dimer, and sCD14 levels were also noted. Use of ECs for 8 weeks does not appear to significantly increase or decrease inflammatory biomarker levels in SWH. Further research with larger samples and a control group is needed. [ABSTRACT FROM AUTHOR]

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), O max (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 (P max) (p  = .04), maximal expenditure (O max) (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. [ABSTRACT FROM AUTHOR]

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), O max (maximum daily expenditure), and P max (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. [ABSTRACT FROM AUTHOR]

This study incorporates intersectionality theory to address potential effects of age on other documented risk factors for current smoking and menthol cigarette use in young adults aged 18-34 using Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study (2013-2014). We explored known correlates of current cigarette and menthol cigarette smoking and interaction analyses by age group (18-24 vs. 25-34), accounting for survey weighting. Use of non-cigarette tobacco products and e-cigarettes was characterized among current cigarette smokers. Young adults experience multiple vulnerabilities to smoking beyond age and some of these known risk factors for smoking place those aged 18-24 at different risk of cigarette smoking compared to their 25-34 year old counterparts. These include lower odds of cigarette smoking by age for sex (female; AOR = 0.62 in those aged 18-24 vs. 0.72 in those aged 25-34) and Hispanic ethnicity (vs. White; AOR = 0.77 vs. 0.45), and higher odds of smoking among past 30-day alcohol users aged 18-24 vs. 25-34 (AOR = 1.62 vs. 1.32). Correlations between lower education and smoking were nearly two-fold higher in 25-34 than 18-24 year olds. Having any medical comorbidity had opposite effects on current smoking by age (18-24 positive correlation, AOR = 1.17; 25-34 negative correlation, AOR = 0.84). Lower education was correlated with menthol cigarette use among young adult smokers. This study suggests that higher smoking prevalence among young adults is associated with the intersection of multiple vulnerabilities to smoking. [ABSTRACT FROM AUTHOR]

A correction to the article "Baclofen as a Pharmacotherapy for the Treatment of Concurrent Alcohol and Nicotine Dependence: A Double-blind, Placebo-Controlled, Randomized Trial" that was published in the previous issue is presented.

Objective: Strong expectations regarding positive effects of smoking may reduce the likelihood of successfully quitting. The Smoking Effects Questionnaire (SEQ) assesses the importance of seven expected positive and negative effects of smoking. SEQ was used to predict responses to contingent monetary rewards for smoking abstinence among smokers with substance use disorders (SUD).Methods: Smokers (N = 184) in residential (i.e., 24 h/day) treatment for SUD received 19 consecutive days of either contingent vouchers (CV) for smoking abstinence (twice-daily carbon monoxide [CO] readings) or non-contingent vouchers (NV) plus counseling to motivate smoking cessation. Analyses investigated effects of smoking expectancies on days of smoking within-treatment and number of cigarettes/day at 1 month post-treatment.Results: Higher positive expectancies for reduced negative affect, weight control, stimulation and positive social effects from smoking were related to more days of smoking during treatment only for participants in the CV condition. Post-treatment, expecting positive social and stimulating effects from smoking were related to more smoking only among CV participants. In both conditions, negative expectancies were largely unrelated to smoking outcomes.Conclusions: The moderation of CV by positive smoking expectancies suggests that those who rate positive expectancies as more important may require a complementary treatment or different incentives to reduce smoking. The SEQ was probably unassociated with smoking in NV due to little reduction in smoking behavior. Helping smokers with SUD develop alternative ways to produce positive effects sought from smoking may be important to improve initial smoking outcomes. [ABSTRACT FROM AUTHOR]

Background: Mandating a reduction in the nicotine content of cigarettes to a minimally addictive level could dramatically reduce smoking rates in the US. However, little is known about the effects of reduced nicotine content cigarettes in adolescents.Methods: Following overnight abstinence, adolescent daily smokers (ages 15-19, n = 50) reported on their craving, withdrawal, and positive and negative affect pre- and post- ad lib smoking of one cigarette containing varying nicotine content (15.8, 5.2, 1.3 and 0.4 mg/g of tobacco) in the laboratory and reported their subjective evaluations of each cigarette. Carbon monoxide (CO) boost from pre- to post-cigarette was calculated to determine if lower-nicotine cigarettes led to differential acute changes in toxicant exposure.Results: All four nicotine cigarette types significantly reduced abstinence-induced craving, withdrawal, and negative affect (all p's < .05). Mixed models evaluating the effect of nicotine content, with nicotine dependence level and gender included as covariates, revealed a significant effect of nicotine content on craving and subjective evaluations: higher nicotine content resulted in greater reductions in craving and increases in both positive and negative subjective evaluations. There were no significant effects of nicotine dose on withdrawal symptoms, negative affect, or CO boost.Conclusions: These results suggest that lower nicotine cigarettes might result in reduced abuse liability compared to higher nicotine content cigarettes due to reduced positive subjective effects, while still reducing withdrawal, in adolescents. These results highlight the potential feasibility of this policy approach and support continued research on how a nicotine reduction policy may affect adolescent smoking patterns. [ABSTRACT FROM AUTHOR]

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 (p s >.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). [ABSTRACT FROM AUTHOR]

Treatment for substance use disorders (SUD) provides an opportunity to use voucher-based treatment for smoking. Nicotine replacement (NRT) could improve outcomes previously observed with vouchers without NRT.Methods: A randomized controlled trial compared contingent vouchers (CV) for smoking abstinence to noncontingent vouchers (NV), when all received counseling and NRT. Smokers who had not sought smoking treatment (n=340) in residential SUD treatment were provided 14days of vouchers for complete smoking abstinence per exhaled carbon monoxide (CO) after a 5-day smoking reduction period, or vouchers only for breath samples, plus brief advice (four sessions) and 8weeks of NRT.Results: Within treatment, 20% had complete abstinence with CV, 5% with NV (p<.001), and participants showed 50% of days abstinent in CV compared to 22% in NV (p<.001). Across 1, 3, 6 and 12months after randomization, CV resulted in significantly fewer cigarettes per day (p<.01) and fewer days smoking (p<.01), but with small effects. Point-prevalence abstinence differences across follow-up (e.g., 4% CV, 2% in NV at 6 and 12months) were not significant. No differences in substance use were seen.Conclusions: Within-treatment effects on abstinence are stronger than in a prior study of the same CV with BA but without NRT, but NRT does not improve abstinence after vouchers end. Implications for voucher-based treatment include investigating effects when combined with stronger smoking medications and using motivational interviewing. Smoking treatment does not harm SUD recovery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Polymorphisms of the μ-opioid receptor (OPRMI) and dopamine D4 receptor (DRD4) genes are associated with subjective responses to alcohol and urge to drink under laboratory conditions. This study examined these associations in the natural environment using ecological momentary assessment. Participants were non-treatment-seeking heavy drinkers (n = 112, 52% female, 61% alcohol dependent) who enrolled in a study of naltrexone effects on craving and drinking in the natural environment. Data were culled from 5 consecutive days of drinking reports prior to medication randomization. Analyses revealed that, after drinking, carriers of the Asp40 allele of the OPRMI gene reported higher overall levels of vigor and lower levels negative mood, as compared to homozygotes for the Asn40 variant. Carriers of the long allele (i.e., ⩾7 tandem repeats) of the DRD4 endorsed greater urge to drink than homozygotes for the short allele. Effects of OPRMI and DRD4 variable-number-of-tandem-repeats genotypes appear to be alcohol dose-dependent. Specifically, carriers of the DRD4-L allele reported slight decreases in urge to drink at higher levels of estimated blood alcohol concentration (eBAC), and Asp40 carriers reported decreases in vigor and increases in negative mood as eBAC rose, as compared to carriers of the major allele for each gene. Self-reported vigor and urge to drink were positively associated with alcohol consumption within the same drinking episode. This study extends findings on subjective intoxication, urge to drink, and their genetic bases from controlled laboratory to naturalistic settings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Because 30% of cigarettes sold in the United States are characterized as menthol cigarettes, it is important to understand how menthol preference may affect the impact of a nicotine reduction policy.Methods: In a recent trial, non-treatment-seeking smokers were randomly assigned to receive very low nicotine cigarettes (VLNC; 0.4 mg nicotine/g tobacco) or normal nicotine cigarettes (NNC; 15.5 mg/g) for 20 weeks. On the basis of preference, participants received menthol or non-menthol cigarettes. We conducted multivariable regression analyses to examine whether menthol preference moderated the effects of nicotine content on cigarettes per day (CPD), breath carbon monoxide (CO), urinary total nicotine equivalents (TNE), urinary 2-cyanoethylmercapturic acid (CEMA), and abstinence.Results: At baseline, menthol smokers (n = 346) reported smoking fewer CPD (14.9 vs. 19.2) and had lower TNE (52.8 vs. 71.6 nmol/mg) and CO (17.7 vs. 20.5 ppm) levels than non-menthol smokers (n = 406; ps < .05). At week 20, significant interactions indicated that menthol smokers had smaller treatment effects than non-menthol smokers for CPD (-6.4 vs. -9.3), TNE (ratio of geometric means, 0.22 vs. 0.10) and CEMA (ratio, 0.56 vs. 0.37; ps < .05), and trended toward a smaller treatment effect for CO (-4.5 vs. -7.3 ppm; p = .06). Odds ratios for abstinence at week 20 were 1.88 (95% confidence interval [CI] = 0.8 to 4.4) for menthol and 9.11 (95% CI = 3.3 to 25.2) for non-menthol VLNC smokers (p = .02) relative to the NNC condition.Conclusions: Although menthol smokers experienced reductions in smoking, toxicant exposure, and increases in quitting when using VLNC cigarettes, the magnitude of change was smaller than that observed for non-menthol smokers.Implications: Results of this analysis suggest that smokers of menthol cigarettes may respond to a nicotine reduction policy with smaller reductions in smoking rates and toxicant exposure than would smokers of non-menthol cigarettes. [ABSTRACT FROM AUTHOR]

Introduction: Young adults (aged 18-24 years) have a higher smoking prevalence than younger and older age groups and young adulthood is an important developmental period during which long-term behavior patterns like cigarette smoking are established. The aim of the current study was to examine how young adult smokers with additional vulnerabilities to smoking respond to reduced nicotine content cigarettes.Methods: This is a secondary analysis of a double-blind, within-subject experiment conducted with 169 cigarette smokers recruited from populations with comorbid psychiatric conditions or socioeconomic disadvantage assessing acute effects of research cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g). Participants were dichotomized by chronological age (18-24 vs. ≥25 years). Across 14 laboratory sessions effects of nicotine content were examined on measures of relative reinforcing efficacy (Cigarette Purchase Task [CPT] and Concurrent Choice testing), subjective effects, craving/withdrawal, and smoking topography. Repeated measures analysis of variances were used to examine potential moderating effects of age.Results: Young adults exhibited lower demand for reduced nicotine content cigarettes than older adults across three of five CPT indices (ps < .05). No differences by age were observed on other measures of reinforcing efficacy, subjective effects, craving/withdrawal, or smoking topography where effects generally decreased as an orderly function of decreasing nicotine content (ps <.05).Conclusion: Overall, these findings suggest that reducing the nicotine content of cigarettes would decrease the addiction potential of cigarette smoking in young adult smokers as much or perhaps more than older adult smokers from populations at increased vulnerability to smoking, addiction, and smoking-related health consequences.Implications: Reducing the nicotine content in cigarettes to lower addiction potential of smoking has been proposed as a means to improve overall population health. It is imperative to examine how young adults may respond to a nicotine reduction policy. We saw minimal evidence that age moderates acute response and where there was evidence it was in the direction of reduced nicotine content cigarettes having less addictive potential among young versus older adults (eg, steeper decreases in demand for very low nicotine content cigarettes among young versus older adults). Overall, a nicotine reduction policy has the potential to reduce smoking across age groups. [ABSTRACT FROM AUTHOR]

Introduction: Minimal research exists on adolescent smokers' perceptions of very low-nicotine-content (VLNC) cigarettes. As approximately half of adolescent smokers prefer menthol cigarettes, it is important to consider the influence of menthol preference on VLNC cigarette perceptions and to what extent menthol preference may affect VLNC smoking behavior. This study examined the effects of cigarette nicotine content and menthol preference or menthol smoking on health risk perceptions, subjective ratings, and carbon monoxide (CO) boost in adolescent smokers.Methods: Across two counterbalanced sessions, adolescent smokers sampled VLNC and normal nicotine content (NNC) research cigarettes following overnight abstinence. Cigarettes were mentholated or non-mentholated consistent with participants' usual brand. In each session, participants smoked the research cigarette and then completed the Perceived Health Risk Scale and Cigarette Evaluation Scale. Breath CO readings were obtained pre- and post-smoking. Mixed-factor ANOVA tests compared outcomes with cigarette type (VLNC vs. NNC) as the within-subjects factor and menthol preference as the between-subjects factor.Results: Participants (N = 50) were M = 17.7 years old, smoked M = 8.2 cigarettes/day, and 56% typically smoked menthol cigarettes. Participants reported lower risk of developing lung cancer, other cancers, emphysema, bronchitis, and heart disease (ps ≤ .05) when smoking VLNC cigarettes relative to NNC cigarettes. Perceived risk of addiction and stroke did not differ by nicotine content. Menthol preference or menthol smoking did not moderate risk perceptions, subjective ratings, or CO boost.Conclusions: Adolescents may incorrectly perceive that VLNC cigarettes are less harmful products. Health communication campaigns could help to correct VLNC misperceptions and potentially minimize unintended consequences of a nicotine reduction policy. [ABSTRACT FROM AUTHOR]

Recent evidence from randomized clinical trials (RCTs) of very low nicotine content (VLNC) cigarettes indicates that smokers randomized to VLNC cigarettes had significantly lower cigarette use, dependence, and biomarkers of exposure than smokers randomized to normal nicotine content control cigarettes. In these trials, a substantial number of participants did not adhere to their randomized treatment assignment, i.e., they used commercial cigarettes not provided by the trial in place of or in addition to the VLNC cigarettes provided by the trial. As with most RCTs, the analysis of these trials followed the intention-to-treat principle, where participants are analyzed according to their randomized treatment assignment regardless of adherence. Alternately, the analysis of an RCT could focus on the estimation and testing of the causal effect of the intervention, which is the treatment effect if all subjects were to adhere to their randomized treatment assignment. In this commentary, we compare these two approaches, highlighting the important role of causal estimation and inference for evaluating the regulatory effect of a nicotine standard for cigarettes. Additionally, we review the results of the secondary analyses of randomized trials of VLNC cigarettes using causal inference methodology to account for non-adherence to the assigned treatment and discuss the implications for a nicotine standard for cigarettes. [ABSTRACT FROM AUTHOR]

Background: Nicotine is the addictive component in cigarettes that maintain cigarette smoking that subsequently leads to morbidity and mortality. Methods for assessing the abuse liability of cigarettes are essential to inform new tobacco product standards. This secondary analysis evaluated the utility of one subjective effects measure, the modified Cigarette Evaluation Questionnaire (mCEQ), and one behavioral economic task, the Cigarette Purchase Task (CPT), for predicting acute relative reinforcing efficacy measured by concurrent choice Self-Administration (SA).Methods: Smokers (N = 169) belonging to one of three vulnerable populations participated in a multi-site, double-blind study evaluating research cigarettes with varying levels of nicotine (0.4, 2.4, 5.2, 15.8 mg/g). Participants sampled cigarettes and completed the mCEQ and CPT. In subsequent sessions, cigarette preference was assessed using a concurrent choice SA procedure. Mixed-model repeated measures analysis of variance tests were used to evaluate the utility of the mCEQ subscales and CPT indices for predicting preference for the higher compared to lower nicotine content cigarettes. In addition, stepwise regressions were used to determine which subscales and indices independently predicted concurrent choice SA.Results: Greater increases on the Satisfaction and Enjoyment of Respiratory Tract Sensations mCEQ subscales independently predicted higher dose preference in concurrent choice testing. Elasticity was the only CPT index that predicted choice. However, its predictive utility differed by dose among opioid-maintained individuals.Conclusion: The mCEQ and CPT predict behavioral measures of relative reinforcing efficacy as assessed in concurrent choice SA, with the mCEQ Satisfaction and Enjoyment of Respiratory Tract Sensations subscales being the strongest independent predictors. [ABSTRACT FROM AUTHOR]