A Method to Amend Cigarettes With Menthol for Use in Research

Introduction Menthol has long been incorporated as a flavor additive in tobacco products and can impact use behaviors. Despite its inclusion in some of the most popular flavored smokeless tobacco (ST) products (e.g., “mint” flavored products), few studies have systematically investigated the impact of menthol on ST use behaviors in prospective empirical studies. Rigorous investigation of ST menthol content on behavioral and physiological outcomes requires ST products with stable and precise levels of menthol; however, commercial product composition variability prevents product comparisons when evaluating the effects of systematic changes in menthol content on clinical outcomes. Methods We developed amended loose moist snuff ST products by treating commercially available, unflavored loose ST with an ethanol-based menthol spiking solution or a nonmentholated ethanol control solution to develop test products with different levels of menthol: 0, 1, 3, and 5 mg menthol/g tobacco. We evaluated the stability of menthol content in these products over 24 months and evaluated menthol exposure associated with the products through pharmacokinetic analysis of plasma menthol-glucuronide in human participants (n=22). Results Menthol content of the amended products was on target, homogenous, and stable for up to 24 months. Menthol exposure (menthol-glucuronide Cmax and AUC) significantly differed between each test product. Conclusions These data suggest that stable products with nonoverlapping menthol content can be developed using a menthol spiking solution and can be subsequently administered for clinical assessments of mentholated loose ST. Implications The results from this study suggest that a menthol spiking solution can be used to mentholate unflavored, loose ST to a target menthol content. With this method, the ST menthol content was stable for at least 24 months, and the products exposed users to menthol in a dose-dependent manner. This method yielded loose ST products with precise, stable levels of menthol to allow systematic evaluation of ST menthol content on clinical outcomes. The method may have applications for systematically evaluating changes in other tobacco product ingredients.

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The Effects of Changes in Cigarette Menthol Content on Acute Nicotine Pharmacology and Smoking Topography

Dimova,

Schroeder,

Pickworth

et al. 2024

Nicotine and Tobacco Research

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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.

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A Method to Amend Cigarettes With Menthol for Use in Research

Cited by 4 publications

References 17 publications

Electrodeposition of paracetamol oxide for intelligent portable ratiometric detection of nicotine and ethyl vanillin β-d-glucoside

Electrodeposition of paracetamol oxide for intelligent portable ratiometric detection of nicotine and ethyl vanillin β-d-glucoside

A Method for Amending Loose Smokeless Tobacco With Menthol for Administration in Clinical Studies

The Effects of Changes in Cigarette Menthol Content on Acute Nicotine Pharmacology and Smoking Topography

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