Anesthetic and synthetic cooling flavors in E-cigarettes: Chemistry and respiratory effects modulating nicotine intake

电子烟中的麻醉剂和合成清凉香料：调节尼古丁摄入量的化学和呼吸效应

• 批准号: 9982329
• 负责人: SVEN-ERIC JORDT
• 金额: $ 47.35万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982329
• 关键词: Adolescent; Advisory Committees; Affect; Afferent Neurons; Aldehydes; Analgesics; Anesthetics; Blood; Calcium; Cells; Chemicals; Chemistry; Chronic; Cigarette; Cigarette Smoker; Clove; Consumption; Cotinine; Data; Dental; Detection; Electronic cigarette; Epidemiology; Eugenol; Family; Family Smoking Prevention and Tobacco Control Act; Flavoring; Gas Chromatography; High School Student; Human; Human Cloning; Image; Industry; Inhalation; Intake; Ion Channel; Ions; Irritants; Liquid substance; Mass Fragmentography; Mass Spectrum Analysis; Measures; Mediating; Menthol; Methods; Microscopic; Modeling; Motion; Mus; Nerve; Neurons; Nicotine; Perception; Pharmacology; Physiological; Plethysmography; Powder dose form; Property; Reader; Rodent; Sensory; Sensory Nerve Endings; Smoker; Sodium; Stimulus; System; TRPV1 gene; Tobacco; Tobacco use; Trigeminal System; Vendor; Youth; addiction; base; cold temperature; cryogenics; design; e-cigarette aerosols; electronic cigarette use; electronic liquid; experimental study; irritation; member; methyl lactate; methyl salicylate; neuronal excitability; novel; ratiometric; receptor; respiratory; response; sensory system; smoking cessation; somatosensory; tobacco products; vaping; vapor; ventilation

SUMMARY The Family Smoking Prevention and Tobacco Control Act (FSPTCA) prohibits the addition of artificial or natural flavors to tobacco cigarettes, with the exception of menthol. While the prohibition of flavored cigarettes in 2009 set in motion a significant decline in youth tobacco use, the proportion of menthol cigarette smokers has increased, suggesting that menthol may promote initation and maintain addiction. Flavor perception results from a synthesis of stimuli carried by gustatory, olfactory and somatosensory nerves. Cooling flavors such as menthol are considered soothing,. TRPM8, a member of the TRP ion channel family, is the target of menthol and other cooling agents in cold-sensing neurons and is also activated by cold temperature. The flavor industry has developed a range of synthetic cooling agents with novel sensory properties. These synthetic cooling agents have been detected in unregulated electronic cigarette liquids and are sold by online vendors as powders or solutions to mix into E-liquids.Other flavorants may also affect properties of sensory systems, including clove flavors, flavored with eugenol, a widely used dental anesthetic, and wintergreen flavors, flavored with methyl salicylate, a topical analgesic. In our preliminary studies we show that synthetic coolants and eugenol strongly activate TRPM8 channels. We performed a chemical analysis of clove-flavored E-liquids, and revealed that some contain very high eugenol levels (>100mM). In mice we observed that menthol reduced respiratory irritation by aldehyde-flavorant containing E-liquids, suggesting that menthol facilitates inhalation. We also observed that menthol increased cotinine levels, suggesting higher nicotine intake. Based on these findings, we hypothesize that some electronic cigarette liquids contain pharmacologically active flavorants that produce vapors with counterirritant or anesthetic effects suppressing respiratory irritation and facilitating initiation of product use. The following specific aims, using analytical chemical, pharmacological and physiological methods, are designed to produce evidence for or against this hypothesis. Aim 1: Determine contents of anesthetic and cooling agents in E-cigarette liquids and condensed vapors Aim 2: Determine pharmacological effects of E-liquids and condensed vapors containing anesthetic or cooling agents on mouse and human irritant receptors and excitability of trigeminal sensory neurons Aim 3: Measure impact of vapor exposure on ventilation and the respiratory irritation response in mice. Due to the close similarities between human and rodent TRP ion channels and their flavorant pharmacology, data resulting from these studies may support efforts to regulate some flavorants as pharmacologically active agents.

总结

项目成果

Tobacco industry's investment in sweetness comes full circle.

烟草业对甜味的投资圆满结束。

• DOI: 10.1136/bmj.l2338
• 发表时间: 2019
• 期刊: BMJ (Clinical research ed.)
• 作者: Jordt,Sven-Eric;Jabba,Sairam
• 通讯作者: Jabba,Sairam

Ice flavours and non-menthol synthetic cooling agents in e-cigarette products: a review.

电子烟产品中的冰口味和非胸膜合成冷却剂：评论。

• DOI: 10.1136/tobaccocontrol-2021-057073
• 发表时间: 2023-11
• 期刊: TOBACCO CONTROL
• 影响因子: 5.2
• 作者: Leventhal, Adam M.;Tackett, Alayna P.;Whitted, Lauren;Jordt, Sven Eric;Jabba, Sairam, V
• 通讯作者: Jabba, Sairam, V

Sweeteners are added to modify consumer behaviour.

添加甜味剂是为了改变消费者的行为。

• DOI: 10.1136/bmj.l366
• 发表时间: 2019
• 期刊: BMJ (Clinical research ed.)
• 作者: Jordt,SvenE;Jabba,Sairam
• 通讯作者: Jabba,Sairam

Chemical Adducts of Reactive Flavor Aldehydes Formed in E-Cigarette Liquids Are Cytotoxic and Inhibit Mitochondrial Function in Respiratory Epithelial Cells.

• DOI: 10.1093/ntr/ntaa185
• 发表时间: 2020-12-15
• 期刊: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco
• 作者: Jabba SV;Diaz AN;Erythropel HC;Zimmerman JB;Jordt SE
• 通讯作者: Jordt SE

Differences in flavourant levels and synthetic coolant use between USA, EU and Canadian Juul products.

• DOI: 10.1136/tobaccocontrol-2019-055500
• 发表时间: 2020-04-27
• 期刊: Tobacco control
• 影响因子: 5.2
• 作者: Erythropel HC;Anastas PT;Krishnan-Sarin S;O'Malley SS;Jordt SE;Zimmerman JB
• 通讯作者: Zimmerman JB