Studying the interactive effects of menthol and nicotine among youth: An examination using e-cigarettes

Abstract

Background: Tobacco products containing menthol are widely used by youth. We used e-cigarettes to conduct an experimental evaluation of the independent and interactive effects of menthol and nicotine among youth.

Procedures: Pilot chemosensory experiments with fourteen e-cigarette users identified low (barely perceptible, 0.5%) and high (similar to commercial e-liquid, 3.5%) menthol concentrations. Sixty e-cigarette users were randomized to a nicotine concentration (0mg/ml, 6mg/ml, 12mg/ml) and participated in 3 laboratory sessions. During each session, they received their assigned nicotine concentration, along with one of three menthol concentrations in random counterbalanced order across sessions (0, 0.5%, 3.5%), and participated in three fixed-dose, and an ad-lib, puffing period. Urinary menthol glucuronide and salivary nicotine levels validated menthol and nicotine exposure. We examined changes in e-cigarette liking/wanting and taste, coolness, stimulant effects, nicotine withdrawal and ad-lib use.

Results: Overall, the high concentration of menthol (3.5%) significantly increased e-cigarette liking/wanting relative to no menthol (p<0.001); there was marginal evidence of nicotine* menthol interactions (p=0.06), with an increase in liking/wanting when 3.5% menthol was combined with 12mg/ml nicotine, but not 6mg/ml nicotine. Importantly, both 0.5% and 3.5% menthol concentrations significantly improved taste and increased coolness. We did not observe nicotine or menthol-related changes in stimulant effects, nicotine withdrawal symptoms or ad-lib use.

Conclusions: Menthol, even at very low doses, alters the appeal of e-cigarettes among youth. Further, menthol enhances positive rewarding effects of high nicotine-containing e-cigarettes among youth.

Keywords: Electronic cigarettes; Menthol; Nicotine; Youth.

Figure 1. Mean “Liking/Wanting” E-cigarette during Fixed-Puffing Period by Nicotine (0, 6 mg/ml, 12 mg/ml) and Menthol Concentration (0, 0.5%, 3.5%)

Note: Main effect of menthol [(F(2,109)=5.46, p=0.006] and a nicotine*menthol interaction [(F(4,109)=2.33, p=0.06)]. The circles (vertical lines through them) represent LS-means (± SE).

Figure 2. Mean “Taste” of E-cigarette in response to No (0%), Low (0.5%) and High (3.5%) menthol

Note: Main effect of menthol [(F(2,111)=5.39, p=0.006]. The bars represent LS-means (± SE).

Figure 3. Mean “Coolness” from E-cigarette in response to No (0%), Low (0.5%) and High (3.5%) menthol

Note: Main effect of menthol [F(2,112)=208.14, p<.0001]. The bars represent LS-means (± SE) of sqrttransformed coolness.

Figure 4

Median (IQR) urine menthol glucuronide (MeG) levels corrected for creatinine (Cr) at baseline and in pooled urine collected during and upon completion of the laboratory session, by menthol concentration (0, LM=0.5%, HM=3.5%).

Figure 5

Median (IQR) salivary nicotine (ng/mL) at baseline and following the 6 and 12 mg/ml nicotine concentrations at the end of the fixed-bout period and at the end of the adlib period (no increases were observed in the 0 mg/ml nicotine condition; data not shown)