Role of mentholated cigarettes in increased nicotine dependence and greater risk of tobacco-attributable disease☆
Introduction
Many investigators have commented that menthol in mentholated cigarettes may enhance the absorption of nicotine without providing a mechanism of action on how this could possibly occur [1], [2], [3], [4], [5].
This paper and its companion paper (PMED2) are the first attempt at developing an understanding of the pharmacological actions of menthol as related to tobacco smoking.
Lloyd Spud Hughes of Mingo Junction, Ohio in the 1920s developed, quite by accident, the first menthol cigarettes called Spud. He had placed the menthol crystals used to treat his cold with his cigarettes in a closed container and the next morning, he had mentholated cigarettes [6].
Menthol has numerous biological actions (Dr. James Duke's USDA Phytochemical database) and has been used for many years in medication for the temporary relief of coughs and minor throat irritation due to colds or inhaled irritants. A previous companion paper [53] has provided evidence linking the continuous delivery of menthol that results from smoking mentholated cigarettes to the masking of the early warning symptoms of respiratory distress.
The upper airway cooling that results from the administration of low dose of menthol [7], [8], [9], [10] like that delivered when smoking mentholated cigarettes may depress respiratory activity. This reduced activity can result in breath holding that results in a greater exposure to nicotine, carbon monoxide and 4000+ other substances delivered in a smoking mentholated cigarette (USDHHS, Smoking Tobacco and Health: A Fact Book, DHHS Publications, (CDC) 87-8377, 1989).
The majority of African-American smokers smoke mentholated cigarettes [11]. African-Americans have higher rates of tobacco-attributable illnesses such as cancer, stroke and heart disease compared to whites [11]. Also, African-Americans may have a higher nicotine dependence than whites [2], [4], [5], [12], [13], [14], [15] even though they smoke fewer cigarettes per day [16], [17], [18], [19] and start smoking at an older age ([13], [14] MMWR Nov 8, 1991/40(434): 754–757).
This paper based on a thorough review of the available literature develops the theoretical framework to logically prove that menthol found in mentholated cigarettes may cause respiratory depression resulting in greater exposure to the toxic substances found in tobacco smoke.
Section snippets
Methods
Based on the thorough literature review, the approach was initially to gather and then piece together all the information on the actions of menthol with emphasis on the pulmonary system. After completing this phase of study, it was determined, based on the literature gathered if these actions would be experienced by the menthol cigarette smoker.
The search procedure was applied generally to the National Library of Medicine (NLM) databases (e.g., MEDLINE from 1966, TOXLINE, OLDMEDLINE from
Menthol's actions—stimulation of cold receptors
Some of menthol's actions on the respiratory tract are the result of stimulation of cold receptors [20]. Menthol at low concentration induces a cold sensation when applied to skin or mucus membranes with the underlying mechanism being a stimulating action on cold receptors (i.e., sensory nerve endings). The stimulation of cold receptors by menthol was independent of any change in temperature [21]. The selective stimulation of cold receptors by menthol is thought to be a result of the inhibition
Conclusion
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The proper amount of menthol per puff on a cigarette can result in the stimulation of cold receptors resulting in the smoker experiencing a “cool sensation.”
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This “cool sensation” causes a reflex inhibition of respiration manifested as breath holding.
- (3)
As a result of breath holding, there is a greater opportunity for exposure and the transfer of the contents of the large surface areas of the alveolar area of the lungs to the pulmonary circulation.
- (4)
For the menthol smoker this results in a greater
Acknowledgements
We would like to thank Professor Ronald Eccles, Director of the Common Cold Center, Cardiff School of Biosciences for being there for us when an expert opinion was needed. Also, we appreciated the input provided by Dr. Stephen Newman former Principal Physicist in the Department of Thoracic Medicine, Royal Free Hospital and School of Medicine whose considered an authority on inhalation drug therapy. In addition, we would like to thank Dr. Michael Cummings, Dr. Gary Giovino and Dr. Andrew Hyland
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Smoking cessation strategies used by former menthol cigarette smokers after a menthol ban
2021, Addictive BehaviorsImpact of menthol on nicotine intake and preference in mice: Concentration, sex, and age differences
2020, NeuropharmacologyCitation Excerpt :One factor known to enhance appeal of tobacco products in humans that could aid in product initiation is flavor additives (Kong et al., 2015; Krishnan-Sarin et al., 2017; Villanti et al., 2017; Wayne and Connolly, 2004). Specifically, menthol cigarette smokers have greater nicotine dependence (Delnevo et al., 2011; Garten and Falkner, 2004; Giovino et al., 2015) and similar tobacco related-health outcomes to non-menthol smokers even though they smoke fewer cigarettes per day (Giovino et al., 2004). Menthol smokers also have a slower nicotine metabolism (Fagan et al., 2016) compared to non-menthol smokers.
History repeats itself: Role of characterizing flavors on nicotine use and abuse
2020, NeuropharmacologyCitation Excerpt :The tobacco industry worked off of this assumption for many years, with documents claiming that tobacco flavor additives (e.g. “vanilla bean, peach, apricot, licorice, cocoa, and many others”) act as masking agents against “objectionable off flavors” (Fries and Brother and Triest; Kostygina et al., 2014; Unknown, 1966). While there is plenty of evidence that menthol reduces irritation caused by nicotine inhalation and leads to increased liking and nicotine consumption (Biswas et al., 2016; DeVito et al., 2019; Fan et al., 2016; Garten and Falkner, 2004; Henderson et al., 2017), evidence that characterizing flavors have this ‘masking’ ability is more sparse. Animal models of drug taking in which bottles of drug are provided to an animal with or without a sweetener (e.g. saccharin) have shown that sweeteners increase nicotine consumption (Smith and Roberts, 1995; Wickham et al., 2018).
Cigarette Smoking Behavior Among Menthol and Nonmenthol Adolescent Smokers
2020, Journal of Adolescent HealthAdolescent menthol cigarette use and risk of nicotine dependence: Findings from the national Population Assessment on Tobacco and Health (PATH) study
2020, Drug and Alcohol DependenceCitation Excerpt :Preclinical data also suggests that menthol enhances the reinforcing properties of nicotine in key brain regions (Biswas et al., 2016; Henderson et al., 2017; Zhang et al., 2018), providing evidence for menthol’s capacity to facilitate nicotine dependence. These unique properties of menthol may collectively lead to a disproportionate increase in the risk of dependence among users of menthol cigarettes relative to those using non-mentholated cigarettes (Fagan et al., 2010; Garten and Falkner, 2004; Hoffman and Simmons, 2011). Despite sound mechanistic data suggesting an association between menthol cigarette use and increased nicotine dependence, relative to non-menthol cigarette use, empirical data to support this association have been inconclusive, especially among adolescents (Curtin et al., 2014).
Activation of the cold-receptor TRPM8 by low levels of menthol in tobacco products
2017, Toxicology LettersCitation Excerpt :Known physiological effects of menthol in the respiratory tract are bronchodilation, decreased rates of inhalation and prolonged breath holding (Henningfield et al., 2003). Menthol does also suppress tussive irritations in response to fumes (Millqvist et al., 2013) and symptoms of respiratory diseases, such as chronic cough or thick mucus production (Garten and Falkner, 2004). The physiological effects of menthol are predominantly related to the activation of the transient receptor potential melastatin 8 (TRPM8) receptor, which is also named cold-menthol receptor (McKemy et al., 2002).
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Funding Sources: No funding was applied for or accepted from tobacco control agencies or pro-tobacco groups that could possibly influence the results of this study.