The National Institutes of Health’s National Institute of Environmental Health Sciences has awarded Duke Anesthesiology’s Sven-Eric Jordt, PhD, a three-year, $1,456,395 R01 grant for his project, titled “Anesthetic and Synthetic Cooling Flavors in E-Cigarettes: Chemistry and Respiratory Effects Modulating Nicotine Intake.”
The Family Smoking Prevention and Tobacco Control Act prohibits the addition of artificial or natural flavors to tobacco cigarettes, with the exception of menthol. Menthol acts as an analgesic and counterirritant by activating the cool-sensing ion channel, TPRM8, in sensory neurons. Intriguingly, the proportion of menthol cigarette smokers has increased, suggesting that menthol may promote initiation and maintain addiction. The flavor industry has developed a range of synthetic cooling agents with novel sensory properties, which 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.
The grant application was supported by crucial preliminary data, generated by Dr. Sairam Venkata Jabba in Dr. Jordt’s Chemical Sensing, Pain and Inflammation Research Laboratory. Dr. Jabba’s experiment shows that synthetic coolants and eugenol strongly activate TRPM8 channels. A chemical analysis of clove-flavored e-liquids revealed that some contain very high eugenol levels.
“Based on these findings, we hypothesize that some e-cigarette liquids contain pharmacologically-active flavorants that produce vapors with counterirritant or anesthetic effects, suppressing respiratory irritation and facilitating initiation of product use,” says Dr. Jordt. “Due to the close similarities between human and rodent transient receptor potential ion channels and their flavorant pharmacology, data resulting from this R01 grant could ultimately support efforts to regulate some flavorants as pharmacologically active agents.”
The Jordt lab will use analytical chemical, pharmacological and physiological methods to determine 1) the contents of anesthetic and cooling agents in e-cigarette liquids and condensed vapors, 2) the 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, and 3) the impact of vapor exposure on ventilation and the respiratory irritation response in mice.
The grant includes a subcontract from Duke to Dr. Julie Zimmerman’s lab in the Department of Chemistry at Yale University who will support the project through analytical chemistry approaches.