More than a "characterizing flavor": Menthol at subliminal levels in tobacco products.

INTRODUCTION: In addition to imparting flavor, menthol in menthol-flavored cigarettes enhances nicotine addiction and increases experimentation, initiation, and progression to regular smoking. Menthol can be added to cigarettes at perceptible levels (so-called flavored cigarettes or characterized flavored cigarettes) or non-perceptible levels (subliminal). Our objective was to understand the reasons that tobacco companies use subliminal menthol. METHODS: We identified previously secret internal tobacco company documents dated 1955-2012 in the Truth Tobacco Industry Documents archive on menthol at subliminal levels. RESULTS: Beginning in at least the 1950s, tobacco companies used subliminal menthol to compensate the flavor loss caused by filters, reduce smoke harshness, reduce dryness, and increase smoke coolness. Varying menthol concentrations were considered to help convert people who smoke non-menthol to menthol brands, possibly because people who use menthol cigarettes have more harship quitting than people who use non-menthol cigarettes. CONCLUSIONS: Menthol is an important additive beyond its function as a "characterizing flavor." Tobacco companies use menthol in "non-menthol" cigarettes at subliminal (non-perceptible by the people who smoke cigarettes) levels to improve taste, make them easier to smoke and facilitate initiation, and possibly convert people who smoke non-menthol cigarettes to menthol cigarettes.

Bioenzyme mediated hydrodistillation (BMHD) for extraction of mint oil from mentha leaves: improvement in yield and menthol content.

The present study optimized pre-treatment conditions for bioenzyme-mediated hydro-distillation (BMHD) for extraction of mint oil from mentha leaves and the results were compared with those of traditional hydro-distillation (HD) method using response surface methodology. The bio-enzymes produced from moringa leaves had maximum pectinase activity (287.04 µg of sugar/min/ml) followed by xylanase (87.78 µg of sugar/min/ml) while endoglucanase, exoglucanase and amylase activities were comparatively low. The optimized conditions for HD were 69.08 temperature for 173.70 min with water:sample of 10.0. The optimized conditions for enzyme pre-treatment of mentha leaves by BMHD were enzyme concentration of 8%, for a period of 120 min at an incubation period of 40 â„ƒ. The yield (%) and menthol content (%) of the oil at optimized conditions by HD were 1.55 ml/100 g of sample and 56.40% menthol content, respectively, and for BMHD the yield and menthol content (%) of the oil at optimized conditions were 3.69% and 72.80%, respectively. It was found that BMHD leads to a 130% increase in the yield of mint oil and a 10% increase in menthol content as compared to the HD method. No significant difference in physical parameters was observed in mint oil extracted via both methods. Therefore, BMHD is a cost-effective and sustainable approach having an edge over the HD method without compromising the quality and could be a viable approach for commercial purposes.

Ecofriendly dual-function cotton fabric with antibacterial and anti-adhesion properties based on modified natural materials.

Ecofriendly fabrics with antibacterial and anti-adhesion properties have been attracted an increasing attention in recent years. Herein, natural menthol modified polyacrylate (PMCA) antibacterial adhesion agent was synthesized by esterification and polymerisation while natural pterostilbene-grafted-chitosan (PGC) antibacterial agent was prepared through Mannich reaction. The antibacterial and anti-adhesion cotton fabric was fabricated through durable PMCA dip finishing and then layer-by-layer self-assembly of PGC. The results showed that the antibacterial adhesion rates and antibacterial rates of the dual-function cotton fabric against Staphylococcus aureus and Escherichia coli reached up to 99.9 %. Its antibacterial adhesion rates improved by 36.1 % and 40.1 % in comparison with those of cotton fabric treated by menthol alone. Meanwhile against S. aureus, the dual-function cotton fabrics improved the antibacterial rates by 56.7 % and 36.4 %, respectively, from those of chitosan- and pterostilbene-treated fabrics. Against E. coli, the improvements were 89.4 % and 24.8 %, respectively. After 20 household washings, the dual-function cotton fabric maintained >80 % of its original anti-adhesion and antibacterial rates against both species. The dual-function cotton fabric also possessed safe and excellent wearability.

Discovery and Engineering of a Bacterial (+)-Pulegone Reductase for Efficient (-)-Menthol Biosynthesis.

The biosynthesis of valuable plant-derived monoterpene (-)-menthol from readily available feedstocks (e.g., (-)-limonene) is of great significance because of the high market demand for this product. However, biotransforming (+)-pulegone into (-)-menthone, the (-)-menthol precursor, through (+)-pulegone reductase (PGR) catalysis is inefficient because of the poor protein expression or catalytic efficiency (kcat/Km) of plant origin PGRs. In this study, a novel bacterial PGR from Pseudomonas resinovorans (PrPGR) was identified, and the most successful variant, PrPGRM2-1 (A50V/G53W), was obtained, showing respective 20-fold and 204-fold improvements in specific activity and catalytic efficiency. PrPGRM2-1 was employed to bioreduce (+)-pulegone, resulting in 4.4-fold and 35-fold enhancements in (-)-menthone titers compared with the bioreductions catalyzed by wild-type (WT) PrPGR and MpPGR, respectively. Furthermore, a whole-cell biocatalyst containing PrPGRM2-1, MpMMR, and BstFDH was constructed and achieved the highest (-)-menthol titer reported to date without externally supplemented NADPH/NADP+. Overall, this study details an efficient PGR with high catalytic efficiency that possesses great potential for (-)-menthol biosynthesis.

KCNQ1 is an essential mediator of the sex-dependent perception of moderate cold temperatures.

Low temperatures and cooling agents like menthol induce cold sensation by activating the peripheral cold receptors TRPM8 and TRPA1, cation channels belonging to the TRP channel family, while the reduction of potassium currents provides an additional and/or synergistic mechanism of cold sensation. Despite extensive studies over the past decades to identify the molecular receptors that mediate thermosensation, cold sensation is still not fully understood and many cold-sensitive peripheral neurons do not express the well-established cold sensor TRPM8. We found that the voltage-gated potassium channel KCNQ1 (Kv7.1), which is defective in cardiac LQT1 syndrome, is, in addition to its known function in the heart, a highly relevant and sex-specific sensor of moderately cold temperatures. We found that KCNQ1 is expressed in skin and dorsal root ganglion neurons, is sensitive to menthol and cooling agents, and is highly sensitive to moderately cold temperatures, in a temperature range at which TRPM8 is not thermosensitive. C-fiber recordings from KCNQ1-/- mice displayed altered action potential firing properties. Strikingly, only male KCNQ1-/- mice showed substantial deficits in cold avoidance at moderately cold temperatures, with a strength of the phenotype similar to that observed in TRPM8-/- animals. While sex-dependent differences in thermal sensitivity have been well documented in humans and mice, KCNQ1 is the first gene reported to play a role in sex-specific temperature sensation. Moreover, we propose that KCNQ1, together with TRPM8, is a key instrumentalist that orchestrates the range and intensity of cold sensation.

Sex differences in appeal, reward, and sensory experience of E-cigarette flavors among adults who smoke cigarettes.

OBJECTIVE: Flavors enhance nicotine e-cigarette appeal by altering sensory experience. Females may be more sensitive to tobacco-associated cues and uniquely affected by flavor. The current study is an exploratory analysis to examine differences by sex on reward, appeal, and sensory experience of popular e-cigarette flavors. METHODS: Adults (N = 121) who use cigarettes (≥1 cigarette/day) were enrolled in a laboratory study in which they vaped four e-cigarette flavors (tobacco, cherry, menthol, vanilla; in separate lab sessions) in one of two freebase nicotine concentrations (6 mg/ml,18 mg/ml). Following exposures, participants rated e-cigarette reward using the Drug Effects Questionnaire (DEQ), flavor and overall e-cigarette appeal using Labeled Hedonic Scales (LHS), and intensity of flavor, irritation, coolness, fruitiness, and sweetness using Generalized Labeled Magnitude Scales (gLMS). Linear mixed models were conducted for outcomes to analyze effects of sex, flavor, and sex x flavor interaction. RESULTS: For DEQ ratings, there was a trend (p = .08) toward a sex x flavor interaction, in which menthol flavor produced more reward than other flavors for females, but not males. For LHS ratings, there was a significant sex x flavor interaction (p = .03) for overall e-cigarette experience with females but not males rating menthol higher than other flavors. All gLMS scales but irritation showed that females generally had greater differences between flavors compared to males (ps ≤ 0.03). CONCLUSION: Menthol in e-cigarettes may play an important role in mediating appeal and/or reward among females. This may be due in part to their ability to better detect sensory effects of e-cigarettes.

Roles of Thermosensitive Transient Receptor Channels TRPV1 and TRPM8 in Paclitaxel-Induced Peripheral Neuropathic Pain.

Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.

e-Cigarette Tobacco Flavors, Public Health, and Toxicity: Narrative Review.

BACKGROUND: Recently, the US Food and Drug Administration implemented enforcement priorities against all flavored, cartridge-based e-cigarettes other than menthol and tobacco flavors. This ban undermined the products' appeal to vapers, so e-cigarette manufacturers added flavorants of other attractive flavors into tobacco-flavored e-cigarettes and reestablished appeal. OBJECTIVE: This review aims to analyze the impact of the addition of other flavorants in tobacco-flavored e-cigarettes on both human and public health issues and to propose further research as well as potential interventions. METHODS: Searches for relevant literature published between 2018 and 2023 were performed. Cited articles about the toxicity of e-cigarette chemicals included those published before 2018, and governmental websites and documents were also included for crucial information. RESULTS: Both the sales of e-cigarettes and posts on social media suggested that the manufacturers' strategy was successful. The reestablished appeal causes not only a public health issue but also threats to the health of individual vapers. Research has shown an increase in toxicity associated with the flavorants commonly used in flavored e-cigarettes, which are likely added to tobacco-flavored e-cigarettes based on tobacco-derived and synthetic tobacco-free nicotine, and these other flavors are associated with higher clinical symptoms not often induced solely by natural, traditional tobacco flavors. CONCLUSIONS: The additional health risks posed by the flavorants are pronounced even without considering the toxicological interactions of the different tobacco flavorants, and more research should be done to understand the health risks thoroughly and to take proper actions accordingly for the regulation of these emerging products.

Menthol-Modified Quercetin Liposomes with Brain-Targeting Function for the Treatment of Senescent Alzheimer's Disease.

Oxidative stress and neuroinflammation in the aging brain are correlated with the development of neurodegenerative diseases, such as Alzheimer's disease (AD). The blood-brain barrier (BBB) poses a significant challenge to the effective delivery of therapeutics for AD. Prior research has demonstrated that menthol (Men) can augment the permeability of the BBB. Consequently, in the current study, we modified Men on the surface of liposomes to construct menthol-modified quercetin liposomes (Men-Qu-Lips), designed to cross the BBB and enhance quercetin (Qu) concentration in the brain for improved therapeutic efficacy. The experimental findings indicate that Men-Qu-Lips exhibited good encapsulation efficiency and stability, successfully crossed the BBB, improved oxidative stress and neuroinflammation in the brains of aged mice, protected neurons, and enhanced their learning and memory abilities.

Mentha spp. essential oils: toxicity to Alphitobius diaperinus, activity against poultry pathogenic bacteria, and Beauveria bassiana compatibility.

The botanical insecticide market is growing because of limitations placed on the use of certain synthetic chemical insecticides. In this sense, the lesser mealworm Alphitobius diaperius (Coleoptera: Tenebrionidae) is the main poultry pest. The insect causes weight loss and damage to the digestive system of poultry, and it is a vector and reservoir of pathogens. Consequently, this study explored the following hypotheses: (i) essential oils (EOs) derived from Mentha spp. are toxic to A. diaperius; (ii) these EOs are compatible with Beauveria bassiana, the natural enemy of the poultry pest, that parasite A. diaperinus; (iii) these EOs also exhibit activity against bacteria that are pathogenic to poultry. In topical applications and ingestion tests, EOs from Mentha arvensis, Mentha spicata, and Mentha piperita were toxic to A. diaperinus. Chromatographic analyses revealed that menthol is the predominant compound in M. arvensis and M. piperita, whereas carvone is the major compound in M. spicata. Both (-)- and (+)-menthol, along with (-)- and (+)-carvone, underwent testing with A. diaperinus. Nevertheless, their activity was not as potent as those of the EOs, suggesting a possible synergistic and/or additive effect. The EOs did not have any adverse effects on the conidial germination, vegetative growth, or conidia production per colony of the entomopathogenic fungus B. bassiana. Consequently, these EOs are compatible with this natural enemy. The EO extracted from M. spicata exhibited significant toxicity against Staphylococcus aureus (ATCC 25923), whereas the remaining EOs displayed moderate toxicity against this bacterium. The EOs derived from Mentha spp., as assessed in this study, hold promise for the development of botanical insecticides tailored for the control of A. diaperinus. These insecticides are selective in favor of the natural enemy B. bassiana and can also serve as effective sanitizers, thanks to their antibacterial properties.

An Estimation of the Prevalence of Smoking and e-Cigarette Use among U.S. Adults If Menthol Cigarettes and Flavored Cigars Are Banned.

INTRODUCTION: People's reaction to the FDA's ban on flavored cigarettes and cigars may be modified by a concurrent ban on flavored e-cigarettes. We aim to estimate the prevalence of smoking and e-cigarette use among U.S. adults under various ban scenarios. METHODS: We collected the reactions of people who used cigarettes, cigars, and e-cigarettes reactions to three hypothetical ban scenarios, (1) restricting menthol cigarettes and flavored cigars only, or (2) further restricting e-cigarettes with any flavors except menthol or tobacco, or (3) further restricting e-cigarettes with all flavors. The above data were analyzed to identify determinants of reactions and to estimate and calibrate the probabilities of quitting and switching to non-flavored cigarettes and cigars. Afterward, the probabilities were applied to 2018-2019 TUS-CPS respondents to estimate the prevalence of smoking and e-cigarette use. RESULTS: Compared with the baseline, the prevalence of smoking decreased from 12.6% to 10.5%, and e-cigarette use increased from 2.6% to 3.8% in Scenario No.1. In Scenario No.2 and No.3, the prevalence of smoking was 10.5% and 10.7%, and the prevalence of e-cigarette use were 3.1% and 2.4%, respectively. For black people, the prevalence of smoking decreased from 14.2% in baseline to 8.1%-8.8% in three scenarios. CONCLUSIONS: The result indicated that for a ban on menthol cigarettes and flavored cigars, a concurrent ban on flavored e-cigarettes with an exemption of menthol flavor could be more effective in encouraging people to quit smoking. Black people may see a disproportionate benefit from all ban scenarios compared with other race/ethics groups.

What is already known on this topic: ban menthol in cigarettes and flavored cigars increases quitting among people who currently smoke.What this study adds: For a ban on menthol cigarettes and flavored cigars, a concurrent ban on flavored e-cigarettes could be complementary if menthol flavor was exempted.How this study might affect research, practice or policy: For flavor bans, inventions to mitigate the increasing use of e-cigarettes and alternative tobacco products are needed, also the interventions should be tailored to various population segments.

Comparison of Menthae Herba written with the same kanji characters () in Japan and China.

Menthae Herba is an herbal medicine whose name is written with the same kanji characters () in both the Japanese Pharmacopoeia, 18th Edition (JP) and in the Pharmacopoeia of the People's Republic of China (CP). However, the original plant are Mentha arvensis Linné var. piperascens Malinvaud in JP and Mentha haplocalyx Briq. in CP. To clarify the similarities and differences between Menthae Herba in Japan and that in China, morphological observations, essential oil component analysis, and DNA analysis were performed on marketed products of Menthae Herba in Japan and in China. The morphological observations based on the description of JP Menthae Herba showed that most of the samples matched the items listed in the description. Essential oil component analysis by gas chromatography-mass spectrometry showed that the amount of menthol varied among samples and that menthol was not always the principal compound in the oil. The original plant species was confirmed by DNA analysis of the rpl16 intron region in chloroplast DNA and all samples matched the sequence of M. canadensis. The results showed that Menthae Herba products distributed in both Japan and China contained M. canadensis, but they had different compositions of essential oil, with menthol-rich Menthae Herba being dominant in the Japanese market.

Comparative Cytotoxicity of Menthol and Eucalyptol: An In Vitro Study on Human Gingival Fibroblasts.

The aim of this study was to assess the influence of eucalyptol and menthol on the cell viability, migration, and reactive oxygen species production of human gingival fibroblasts (GFs) in vitro. Three different concentrations of eucalyptol and menthol were prepared following ISO 10993-5 guidelines (1, 5, and 10 mM). GFs were isolated from extracted teeth from healthy donors. The following parameters were assessed: cell viability via MTT, Annexin-V-FITC and 7-AAD staining, and IC50 assays; cell migration via horizontal scratch wound assay; and cell oxidative stress via reactive oxygen species assay. Data were analyzed using one-way ANOVA and Tukey's post hoc test. Statistical significance was established at p < 0.05. Eucalyptol and Menthol exhibited high cytotoxicity on gingival fibroblasts, as evidenced by cytotoxicity assays. Eucalyptol showed lower levels of cytotoxicity than menthol, compared to the control group. The cytotoxicity of the tested substances increased in a concentration-dependent manner. The same occurred in a time-dependent manner, although even 10 min of exposure to the tested substances showed a high cytotoxicity to the GFs. Commercially available products for oral application with these substances in their composition should be tested for cytotoxicity before their use.

Antinociceptive Analysis of Natural Monoterpenes Eugenol, Menthol, Carvacrol and Thymol in a Zebrafish Larval Model.

In the last decade, a considerable number of studies have broadened our knowledge of the nociceptive mechanisms of pain, a global health problem in both humans and animals. The use of herbal compounds such as eugenol, menthol, thymol, and carvacrol as analgesic agents has accompanied the growing interest in this area, offering a possible solution for this complex problem. Here, we aimed to explore how these natural substances-at three different concentrations (2, 5 and 10 mg/L)-affect the pain responses in zebrafish (Danio rerio) larvae exposed to 0.05% acetic acid (AA) for 1 min. By analysing the activity of acetylcholinesterase (AChE), 5'-ectonucleotidase and NTPDases, as well as aversion and exploratory behaviours, it was observed that that although all substances were effective in counteracting the pain stimulus, the concentration range within which they do so might be very limited. Eugenol, despite its acknowledged properties in fish anaesthesia, failed to alleviate the pain stimulus at low concentrations. Contrastingly, menthol exhibited the most promising results at the lowest concentrations tested. Overall, it is concluded that menthol might be a good analgesic for this species, qualifying it as a substance of interest for prospective studies.

DFT Studies of the Activity and Reactivity of Limonene in Comparison with Selected Monoterpenes.

Nowadays, the effective processing of natural monoterpenes that constitute renewable biomass found in post-production waste into products that are starting materials for the synthesis of valuable compounds is a way to ensure independence from non-renewable fossil fuels and can contribute to reducing global carbon dioxide emissions. The presented research aims to determine, based on DFT calculations, the activity and reactivity of limonene, an organic substrate used in previous preparative analyses, in comparison to selected monoterpenes such as cymene, pinene, thymol, and menthol. The influence of the solvent model was also checked, and the bonds most susceptible to reaction were determined in the examined compounds. With regard to EHOMO, it was found that limonene reacts more easily than cymene or menthol but with more difficultly than thymol and pienene. The analysis of the global chemical reactivity descriptors "locates" the reactivity of limonene in the middle of the studied monoterpenes. It was observed that, among the tested compounds, the most reactive compound is thymol, while the least reactive is menthol. The demonstrated results can be a reference point for experimental work carried out using the discussed compounds, to focus research on those with the highest reactivity.

The Effect of Menthol Mouth Rinsing and Fluid Temperature on Male Cycling Performance in Thermoneutral Conditions.

PURPOSE: The purpose of this study was to determine the effect of a menthol (MEN) mouth rinse (MR) on cycling time trial (TT) performance in thermoneutral conditions and to explore the impact of fluid temperature (cold water [CW] or thermoneutral water [TNW]) on MEN's effect on performance. METHODS: Twelve trained male cyclists (VO2 peak, 61.4 ± 12.1 mL/kg/min) completed a cycling TT in thermoneutral conditions (21 ± 0.2 °C, 40 ± 0.6% relative humidity) with four different mouth rinses: (1) MEN + CW; (2) MEN + TNW; (3) CW; and (4) TNW. The time to complete the TT and the power output (W) were recorded. The ratings of perceived exertion (RPE, Borg 6-20), thermal sensation (TS), and thermal comfort (TC) were recorded prior to and throughout the TT. The core body temperature (Tc) and heart rate (HR) were recorded throughout. RESULTS: The TT duration was not significantly different between trials (MEN + TNW: 38:11 ± 12:48, MEN + CW: 37:21 ± 13:00, CW: 38:12 ± 13:54, TNW: 36:06 ± 14:12 mins:secs, p < 0.05). The mean trial power output did not significantly differ between conditions (>0.05). The Tc, HR, RPE, TS, and TC were not significantly different between trials (p > 0.05). CONCLUSION: The results suggest that a MEN MR with either CW or TNW does not significantly improve cycling TT performance in trained male cyclists compared to a CW or TNW MR in thermoneutral conditions.

Menthol versus tobacco e-liquid flavor: Impact on acute subjective effects, puff patterns, and intentions for use among Black and White menthol smokers.

BACKGROUND: The proposed FDA product standard to prohibit menthol as a characterizing flavor in combustible cigarettes has the potential to significantly reduce tobacco-related health disparities. Whether a menthol e-liquid product standard would improve or hinder public health is unknown. No known research has directly examined the impact of menthol vs. tobacco flavored e-liquid use on acute e-cigarette use patterns, subjective experience, behavioral intentions, and craving and withdrawal among menthol cigarette smokers. METHODS: Black (n = 47) and White (n = 4) nicotine-deprived menthol smokers with limited e-cigarette experience completed two counterbalanced in-laboratory 30-minute ad libitum vaping sessions with menthol and tobacco nicotine salt-based e-liquid in a randomized crossover pilot trial design. Questionnaires assessed reductions in craving and withdrawal and post-session subjective experience and behavioral intentions. Puff topography was measured continuously throughout each vaping session. RESULTS: Measures of puff topography did not differ significantly by e-liquid flavor (all p > .40). Similarly, menthol and tobacco flavored e-cigarettes were both rated positively in terms of subjective effects and behavioral intentions (all p > .10) and about 40 % of participants reported a preference for the tobacco-flavored e-liquid. Finally, participants showed comparable reductions in craving (p = .210) and withdrawal (p = .671) from pre- and post-session regardless of e-liquid flavor. CONCLUSIONS: Among menthol smokers in a lab-based setting, findings suggest that menthol vs tobacco e-liquid flavor has little impact on acute changes in puff patterns, subjective experience, behavioral intentions, or craving and withdrawal.

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

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

Prevalence of menthol cigarette use among adults who smoke from the United States by census division and demographic subgroup, 2002-2020: findings from the International Tobacco Control (ITC) project.

BACKGROUND: Targeted marketing of menthol cigarettes in the US influences disparities in the prevalence of menthol smoking. There has been no analysis of sub-national data documenting differences in use across demographic subgroups. This study estimated trends in the prevalence of menthol use among adults who smoke in the nine US census divisions by sex, age, and race/ethnicity from 2002 to 2020. METHODS: Data from 12 waves of the US ITC Survey were used to estimate the prevalence of menthol cigarette use across census divisions and demographic subgroups using multilevel regression and post-stratification (n = 12,020). Multilevel logistic regression was used to predict the prevalence of menthol cigarette use in 72 cross-classified groups of adults who smoke defined by sex, age, race/ethnicity, and socioeconomic status; division-level effects were fit with a random intercept. Predicted prevalence was weighted by the total number of adults who smoke in each cross-classified group and aggregated to divisions within demographic subgroup. Estimates were validated against the Tobacco Use Supplement to the Current Population Survey (TUS-CPS). RESULTS: Overall modeled prevalence of menthol cigarette use was similar to TUS-CPS estimates. Prevalence among adults who smoke increased in each division from 2002 to 2020. By 2020, prevalence was highest in the Middle (46.3%) and South Atlantic (42.7%) and lowest in the Pacific (25.9%) and Mountain (24.2%) divisions. Prevalence was higher among adults aged 18-29 (vs. 50+) and females (vs. males). Prevalence among non-Hispanic Black people exceeded 80% in the Middle Atlantic, East North Central, West North Central, and South Atlantic in all years and varied most among Hispanic people in 2020 (Pacific: 26.5%, New England: 55.1%). CONCLUSIONS: Significant geographic variation in the prevalence of menthol cigarette use among adults who smoke suggests the proposed US Food and Drug Administration (FDA) menthol cigarette ban will exert differential public health benefits and challenges across geographic and demographic subgroups.

Assessment of abuse liability and switching potential of menthol-flavored pod-based electronic nicotine delivery systems among US adults who smoke cigarettes.

BACKGROUND: Menthol-flavored electronic nicotine delivery systems (ENDS) are a focus of public health and regulatory policy considerations. The abuse liability of five menthol-flavored pod-based ENDS was compared to combustible cigarettes, and switching potential of ENDS was also evaluated. METHODS: 215 US adults who smoke cigarettes (34.4% female; mean age[SD]=29.60[8.75]; 40.9% non-Hispanic White; mean cigarettes/day[SD]=12.04[8.52]) completed a randomized 6-arm within-person cross-over product-use study. Participants used five pod-based menthol-flavored ENDS (JUUL2 Polar Menthol 1.5%, JUUL2 Prototype Fresh Menthol 3.0%, JUUL Menthol 5.0%, Vuse Alto Menthol 5.0%, NJOY Ace Menthol 5.0%) and their usual brand (UB) cigarette for 20minutes ad libitum. After each product use, subjective reinforcing effects relevant to abuse liability and associated with switching away from cigarettes (e.g., satisfaction, product liking) were assessed. RESULTS: All ENDS products were rated substantially and statistically significantly lower than UB cigarette on measures of subjective reinforcing effects (ps<0.001). Satisfying effects of JUUL2 1.5% were rated significantly higher than other ENDS products. JUUL2 Prototype 3.0% and Vuse Alto 5.0% did not significantly differ (ps>0.05), and both were rated significantly higher than JUUL 5.0% and NJOY Ace 5.0% (ps<0.05). Differences in subjective responses to study products did not significantly differ by preference for menthol cigarettes or by current ENDS use. CONCLUSIONS: Abuse liability of all menthol-flavored ENDS in this study was substantially lower than combustible cigarettes. Abuse liability of JUUL2 1.5% was within the range of currently marketed pod-based menthol-flavored ENDS products. JUUL2 1.5% likely has high potential for facilitating switching among US adults who smoke.