IntroductionCigarillos dominate the US cigar market, and young adults largely drive use. While young adults prefer flavoured to non-flavoured cigarillos, especially those flavoured to taste like fruit or other sweets, the factors that underlie this preference have received little attention. We sought to determine if key indicators of abuse liability, the rewarding and reinforcing effects, are greater for sweet versus non-flavoured cigarillos.MethodsYoung adults (18–24 years old) completed three laboratory visits assessing the subjective rewarding value (exposure paradigm), relative reinforcing value (computerised choice task) and absolute reinforcing value (ad libitum cigarillo smoking session) of sweet-flavoured versus non-flavoured cigarillos. General linear regression models were fit with the appropriate family link for each outcome measure.ResultsYoung adults rated sweet-flavoured cigarillos as more rewarding (estimated marginal mean (EMM) =4.52, 95% CI 4.00 to 5.03) than the non-flavoured cigarillo (EMM=3.31, 95% CI 2.80 to 3.83; B=1.20, 95% CI 0.80 to 1.60, p<0.001). The reinforcing value of sweet-flavoured cigarillos, measured by break point, was higher relative to non-flavoured cigarillos (6.34 out of 10), especially among young adults with a preference for flavoured cigarillos (B=1.94, 95% CI 0.71 to 3.18, p=0.003). Young adults took 1.9 times the number of puffs (35.75 vs 19.95) from sweet-flavoured cigarillos compared with non-flavoured cigarillos (Rate Ratio =1.94, 95% CI 1.30 to 2.90, p<0.001).ConclusionsSweet flavouring increases the abuse liability of cigarillos among young adults as reflected in greater liking, motivation to use and actual use. Banning sweet flavouring in cigarillos may diminish their use in young adults.Trial registration number CT.gov (NCT05092919).

Menthol smoking, which is popular among Black and Hispanic individuals who smoke and young adults, is linked to positive subjective effects and difficulty quitting, although studies of topography and subjective effects show inconsistent differences. This study compared subjective effects and laboratory smoking across menthol and nonmenthol young adults who smoke and examined differences by race/ethnicity. Smoking topography, subjective effects, and pre/postsmoking craving, vitals, cigarette weight, and exhaled carbon monoxide were assessed in 121 young adults who smoke (Mage = 23.9; 49.5% menthol; 37.2% non-White) following ≥12 hr of abstinence. Participants smoked their usual brand cigarette (menthol or nonmenthol) in a single laboratory session. Differences in study outcomes were examined across cigarette flavor and by race/ethnicity (White vs. non-White). No main effects of cigarette flavor or race/ethnicity emerged on any study outcomes. Interactions of cigarette flavor with race/ethnicity emerged on postsmoking craving and cigarette weight, controlling for presmoking measures of the outcome and cigarettes per day. Compared to non-White participants who smoked nonmenthol cigarettes, non-White participants who smoked menthol cigarettes had higher postsmoking cigarette weight and lower postsmoking craving. Further, non-White participants who smoked menthol cigarettes had lower postsmoking craving compared to White participants who smoked menthol cigarettes. Non-White young adults who smoke menthols experienced greater craving reduction, despite consuming less of their preferred cigarette. Craving reduction may be one mechanism fostering continued menthol smoking. Menthol smoking, even at lower amounts, produces similar toxicant exposure, which may contribute to tobacco health disparities as smoking progresses. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Introduction Menthol influences the appeal and addictiveness of cigarette smoking, however the data regarding menthol's effects on nicotine pharmacokinetics (PK) and smoking topography are inconsistent. This study investigated the impact of different cigarette menthol levels on nicotine pharmacology and smoking topography in current menthol smokers.Aims and Methods The study was a double-blind, randomized, four-period, crossover study to investigate the effects of smoking cigarettes with varying menthol content (0, 3, 6, and 12 mg menthol) on nicotine PK, smoking topography, and subjective effects in current menthol smokers. Each experimental session consisted of a prescribed use session, followed by 145 min of no smoking and a 1-h ad libitum smoking session. Serial blood samples were collected; smoking topography was recorded using CReSS Lab topography device.Results There was no significant effect of menthol on nicotine PK after prescribed smoking of cigarettes with varying menthol contents. During ad libitum smoking, there was significantly smaller total puff volume and puff duration in the 12 mg menthol condition compared to other menthol conditions. Subjective and sensory measures indicated significantly higher overall positive ratings for the 3 mg and 6 mg menthol cigarettes compared to the 0 mg menthol cigarette; the 12 mg menthol cigarette was less liked and harsher than the 3 mg condition.Conclusions These findings suggest that menthol, at concentrations reflecting the marketplace (3-6 mg), contributes to positive subjective smoking experiences among menthol smokers, but does not have a significant effect on nicotine PK or smoking topography in an acute laboratory setting.Implications While our data indicate that varying menthol content does not have a significant impact on nicotine's pharmacological effects under acute exposure conditions, these data highlight the contribution of menthol's flavor and sensory effects to product preference and positive smoking experiences, which facilitate repeated experimentation, progression to regular use, and subsequent dependence.

Introduction: Menthol cigarettes are associated with experimentation and progression to regular use. Although reinforcement processes likely underlie menthol's appeal, the reinforcing value of menthol cigarettes remains unknown. Aims and Methods: This study examined the relative reinforcing value (RRV) of menthol versus nonmenthol cigarettes in young adult menthol (n = 54) and nonmenthol (n = 53) smokers, and differences in menthol's RRV by race, ethnicity, and sexual orientation. Overnight abstinent participants completed a choice task assessing willingness to "work" to click targets on a computer screen to earn menthol or nonmenthol cigarette puffs. A progressive ratio schedule was used where the menthol target had to be clicked progressively more times, over 10 trials, to earn a menthol cigarette puff, while clicks for the nonmenthol target were fixed across trials. RRV for menthol was defined by the breakpoint, or the highest trial (out of to 10) completed for a menthol cigarette puff. Number of clicks for menthol and nonmenthol puffs were also examined. Results: Menthol smokers worked harder for menthol versus nonmenthol cigarette puffs (breakpoint = 9.17; similar to 1236 clicks vs. 24 clicks). Breakpoint was higher among Hispanic (6.49) versus NH White (4.83) and NH non-White smokers (4.43). In exploratory analyses of interactions of menthol preference with race and ethnicity, nonmenthol Hispanic smokers worked harder for menthol cigarette puffs versus NH non-White and NH White nonmenthol smokers. Conclusions: Menthol cigarettes are highly reinforcing for young adult menthol and Hispanic smokers. A menthol ban may reduce addiction risk among younger individuals and some minoritized groups of smokers.

Correlation of the 2nd CO boost to smoking-related variables.

Correlation of the significant metabolite boosts from the 2nd cigarette to smoking-related variables.

Alcohol and tobacco use are interrelated. This study examined response to very low nicotine content (VLNC) and moderate nicotine content (MNC) cigarettes by problematic drinking. We utilized a double-blind, randomized, within-subjects crossover design of VLNC and MNC cigarettes in two groups of adult cigarette smokers: with at-risk drinking (ARD; n = 23) and without ARD (n = 24). Participants smoked only their assigned experimental cigarette in their home environment for 7 days, and completed laboratory visits, including ad libitum smoking of the assigned experimental cigarette, at the beginning and end of each experimental week. Participants smoked their usual cigarettes for 7 days between conditions. Participants provided daily reports of alcohol and cigarette consumption. Current Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) alcohol use disorder (AUD) was assessed at baseline and the end of each experimental week. Compliance with smoking of experimental cigarettes was good. Adjusting for baseline drinking, there was no significant effect of experimental cigarette or ARD group on drinks per day or alcohol urges. There was no effect of experimental cigarette or ARD group on cigarettes per day, or on any puff topography outcome or postsmoking exhaled carbon monoxide during laboratory smoking. No participant had a change in AUD status or AUD severity. After 7 days of exposure to VLNC cigarettes, adult cigarette smokers with ARD did not show compensatory drinking or compensatory smoking behavior. A future policy change in the United States to reduce nicotine content in cigarettes may not produce unintended compensatory drinking or smoking among this vulnerable and prevalent population of smokers. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Introduction Studies have evaluated the role of menthol cigarettes on various addiction-related outcomes; however, the effect of varying menthol content on these outcomes has not been evaluated. We developed a method to amend non-menthol SPECTRUM Research Cigarettes to contain menthol at four different levels. Aims and Methods SPECTRUM Research Cigarettes, NRC 600 (0.8 mg nicotine; 10 mg tar), were modified to contain target menthol amounts at 3, 6, and 12 mg/cigarette by injecting 25 mu L ethanol/triacetin/menthol solutions of varying concentrations (120 mg menthol/mL, 240 mg/mL, and 480 mg/mL) into four distinct locations in the filter and tobacco rod. Menthol content was tested in triplicate in the whole cigarette and in the tobacco rod and filter at 1, 24, 48, and 72 hours for each target menthol level using an extraction solution of quinoline in methyl-tert-butyl ether and measured using gas chromatography with flame ionization detection. Results Injections into the filter and tobacco rod (12.5 mu L each) yielded equal menthol distribution up to 72 hours. However, total menthol content decreased from an average of 90.3% of the target menthol concentration at 1 hour to 80.7% at 72 hours in cigarettes stored individually in glass tubes at room temperature. Analysis of urinary menthol glucuronide confirmed that amended cigarettes used within 24 hours of injection delivered dose-related menthol levels to participants in a clinical laboratory setting. Conclusion This method can be used to modify cigarettes with a range of reliable menthol levels in both filter and tobacco rod for use in laboratory and clinical research. Implications This study presents a technique for modifying cigarettes with different levels of menthol that can reliably deliver dose-related menthol levels to participants when smoked in a clinical study. The technique can be used to quickly amend cigarettes to examine the independent effects of varying flavor and additive levels on smoking behavior, nicotine pharmacokinetics, mainstream smoke emissions, and other laboratory or clinical research outcomes.

Introduction An Internet questionnaire was used to determine smoking behavior, purchasing behavior, and risk perceptions among exclusive or nearly exclusive current users of either large manufactured (LMC) or premium cigars (PC). Aims and Methods Respondents (n = 250) were recruited from a nationally representative market research panel. An a priori designation of PC users was adapted from criteria in published literature and the recent National Academy of Science report. Results Examination of responses revealed a (n = 19) disagreement between cigar users' self-classifications and the a priori classification. After eliminating ineligible respondents 188 participants were classified as PC (n = 92; 55 male) or LMC (n = 96; 49 male) users. There were no significant differences in age or gender between groups. Respondents were all over 21 years old. The largest age groups were 30-39 years and 60-69 years. PC users were significantly more likely to have higher annual incomes and to buy cigars online or through tobacco specialty shops, whereas LMC users purchased from convenience stores. Most participants had used other combustible tobacco products (88%) but few had used ENDS (24%) or oral tobacco (7.5%). There was no significant difference in the frequency of smoke inhalation or perceptions of risk for health. There was marked uncertainty in self-characterization of cigar type; our sample had higher female representation than expected (n = 84, 45%), and inhalation was frequently endorsed in both groups (52%, overall). Conclusions The results support the need for standardized classifications and suggest current trends may indicate shifts in gender and use behavior but provide no evidence supporting less restrictive regulation of PC. Implications An Internet questionnaire was used to determine smoking behavior, purchasing behavior, and risk perceptions among current users of LMC or PC. There was uncertainty about cigar classification even in this sample of regular users. Our results demonstrated more than expected inhalation of cigar smoke, considerable use by females, and under appreciation of health risks. No results supported less restrictive regulations for premium cigars.

Correlation of pre- and post-cigarette MG levels to topography profiles.

Introduction Moist snuff smokeless tobacco (ST) products are available in the United States in both "loose" and "portioned" (ie, pouched) formats, but no published study to date has clinically evaluated the associations between ST format, use behavior, and nicotine exposure. Aims and Methods Participants used their usual brand of ST (loose ST [n = 30] or portioned ST [n = 20]) during an experimental visit wherein use behavior and plasma nicotine pharmacokinetic parameters were measured following single use (first hour of the session) and ad libitum use (remaining 7 h of the session). Participants' ST products were chemically characterized prior to use for pH and nicotine content. Results The average amount per use (2.99 vs. 1.52 g; p = .005) and total amount used (11.45 vs. 5.4 g; p = .002) were significantly higher among the loose ST group. Maximum plasma nicotine concentration (C-max; 33.4 vs. 19.1 ng/ml) and area under the nicotine concentration versus time curve (AUC) were significantly higher for the loose ST group for the first hour (1474.8 vs. 807.2 min* ng/ml; p = .003) and throughout the 8-hour session (15827.9 vs. 8155.3 min* ng/ml; p < .001). Significant associations were observed between free nicotine content and first use C-max (r(s) = .488, loose ST group) and AUC(0-1 h) (r(s) = 0.448, loose ST group; r(s) = .441, portioned ST group). Conclusions The loose ST group used more product and had a greater average deposition time per use than the portioned ST group. Nicotine exposure was more strongly associated with free nicotine content than total nicotine content. Implications To our knowledge, the current investigation was the first study to date to clinically evaluate the associations between usual-brand smokeless format, use behavior, and nicotine exposure. We observed meaningful differences in use behavior and subsequent nicotine exposure between loose and portioned ST users. Further, we observed that nicotine exposure was more strongly associated with free nicotine content than total nicotine content.

Correlation of the 2nd nicotine boost to smoking-related variables.

Little filtered cigars are tobacco products with many cigarette-like characteristics. However, despite cigars falling under the U.S. Food and Drug Administration regulatory authority, characterizing flavors, which are still allowed in little filtered cigars, and filter design may influence how people use the products and the resulting exposure to harmful and potentially harmful constituents. We estimated nicotine mouth level intake (MLI) from analyses of little cigar filter butt solanesol levels, brand characteristics, carbon monoxide boost, and puff volume in 48 dual cigarette/cigar users during two repeat bouts of ad lib smoking of three little filtered cigar brands. Mean nicotine MLI for the three brands was significantly different with Swisher Sweets (0.1% ventilation) Cherry at 1.20 mg nicotine, Cheyenne Menthol (1.5%) at 0.63 mg, and Santa Fe unflavored (49%) at 0.94 mg. The association between nicotine MLI and puff volume was the same between Cheyenne Menthol and Santa Fe unflavored. However, these were different from Swisher Sweets Cherry. At least five main factors─flavor, ventilation, filter design, nicotine delivery related to tar, and user puff volume─may directly or indirectly impact MLI and its association with other measures. We found that users of little filtered cigars that have different filter ventilation and flavor draw dissimilar amounts of nicotine from the product, which may be accompanied by differences in exposure to other harmful smoke constituents.

Models determining the correlations of the MG boost to smoking-related variables.

Abstract The rate of nicotine absorption from tobacco products is a determinant of addiction potential and other detrimental health effects. Oral nicotine bioavailability from moist snuff smokeless tobacco (ST) is influenced by nicotine content, pH, flavors, and tobacco cut. For use in a clinical study testing the effect of pH on nicotine pharmacokinetics, four investigational ST products that differed only in pH were produced. A commercial ST product (Copenhagen Long Cut Original, pH 7.7) was modified with citric acid monohydrate (23 mg/g tobacco) or sodium carbonate (4.6 and 11 mg/g) to create products with pH 5.0, 8.2, and 8.6, respectively. All products – including the original product with pH 7.7 – were individually packaged (approximately 2 g) in aluminum foil pouches and stored frozen (−20 °C); pH, nicotine, tobacco-specific nitrosamines, moisture content, and mold and yeast counts were tested for up to 19 months to verify stability. Remarkable stability was demonstrated in this packaging/storage combination. For example, pH from all products were within 0.1 pH units and never exceeded 0.2 units. Nicotine concentration averaged 9.07 mg/g at baseline, maximal deviations from baseline in the four products averaged 0.30 mg/g. Similarly, TSNA, moisture content, yeast, and mold did not materially change. This study illustrates a method of investigational tobacco products formulation by manipulating a single design feature (or component) with the purpose of independently and systematically assessing its influence on nicotine bioavailability in a clinical study.

Nicotine absorption rate influences tobacco products' addictiveness. For smokeless tobacco, nicotine buccal absorption is associated with its free-base form; the pH of smokeless tobacco defines the proportion of free-base (i.e., unprotonated) vs. protonated nicotine. This was the first study to compare nicotine pharmacokinetics (PK) and pharmacodynamics (PD) after the use of commercial smokeless tobacco products that were experimentally manipulated to differ only in pH and percent free-base nicotine. Moist snuff users (N = 40) completed four crossover visits and used a single 2 g portion of Copenhagen Original Long Cut amended to 4 pH levels: 5.0, 7.7, 8.2, and 8.6 (free-base nicotine 0.1, 32, 60, and 79%) for 30 minutes. Nicotine PK and PD were assessed for 4 hours post-use. Nicotine PK substantially depends on its free-base proportion, with more than 4-fold increases in mean plasma nicotine maximum concentration and area under the curve over 240 minutes (3.9 to 16.7 ng/mL; 385 to 1810 ng min/mL, respectively, both P < 0.001) from pH 5.0 to 8.6. The autonomic cardiovascular effects of smokeless tobacco use reflected percent free-base nicotine, with small (albeit significant) systematic increases in heart rate and blood pressure associated with free-base nicotine. Smokeless tobacco product pH and percent free-base nicotine play a major role in the rate and extent of nicotine absorption, determining product PD effects and abuse potential. Research and regulation of smokeless tobacco products should consider both total nicotine content and product pH. Further research may address the impact of modifying pH on the addictiveness of smokeless tobacco and associated use behaviors.

Introduction Although the Food and Drug Administration banned other characterising flavours in cigarettes, menthol cigarettes are still available to consumers. Young adult new smokers are initiating with menthol cigarettes, such that the prevalence of young adults menthol versus non-menthol smokers is increasing. Experimentation with menthol cigarettes is associated with progression to regular smoking and nicotine dependence. This ongoing clinical trial in young adult smokers measures appeal and the reinforcing value of smoking menthol versus non-menthol cigarettes and the impact of these variables on changes in smoking behaviour at a 6-month follow-up. Methods and analysis Reinforcement for menthol smoking is assessed in the laboratory using a validated behavioural economic choice task, and appeal is measured in the natural environment using ecological momentary assessment (EMA). Analyses will examine differences between menthol and non-menthol cigarette smoking on measures of subjective response in the laboratory and via EMA, and how subjective response mediates the association between menthol preference at baseline and smoking outcomes at follow-up. Ethics and dissemination This protocol was approved by the University of Oklahoma Health Sciences Center Institutional Review Board (#10581). The findings will isolate the unique effects of menthol in smoking and will help inform regulatory decisions about the abuse liability of menthol cigarettes. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences. Trial registration number NCT03953508 .

Co-users of cannabis and tobacco frequently use cannabis, then tobacco cigarettes, in a sequential pattern within an occasion, that is, they "chase" smoked cannabis with a tobacco cigarette. The objective of this placebo-controlled, double-blind, within-subjects human laboratory study was to gather preliminary data on how smoking active versus placebo cannabis impacts tobacco cigarette smoking behavior, craving, and subjective effects. Adult daily cannabis and tobacco co-users (N = 9) were randomly assigned to two experimental visit orders (i.e., active cannabis (5.2% THC) first visit and placebo cannabis second visit, or vice versa). Participants smoked one cannabis cigarette, and approximately 30 min later were given a 5-min ad libitum period to smoke one of their own brand of tobacco cigarette. As expected, boost in plasma THC levels and cannabis-related subjective effects differed between active and placebo cannabis conditions. Tobacco cigarette puff topography measures and tobacco craving did not differ between cannabis conditions, but there appeared to be between-participants heterogeneity in cumulative total puff volume. After smoking active versus placebo cannabis, the changes in subjective effects of tobacco smoking after adjusting for pretobacco smoking levels were not significant. Results do not support the notion that immediate effects of smoked cannabis change the behavior of tobacco smoking. The strong overlap between cannabis and tobacco smoking may not be explained by primarily pharmacological factors, but may be driven by more nuanced and complex mechanisms involving pharmacological processes as well as learning factors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).