The effects of menthol content on the abuse liability of smokeless tobacco in a randomized crossover trial.

Background: Menthol is a common additive in tobacco products and reduces the aversiveness of nicotine. While numerous studies have examined the effects of menthol in cigarettes on nicotine exposure and other addiction-related outcomes, no clinical study to date has investigated the influence of menthol on nicotine pharmacokinetics (PK) and abuse liability in smokeless tobacco (ST).

Aims: The current study investigated the effects of varying levels of menthol in ST on nicotine PK, pharmacodynamics (i.e., heart rate and blood pressure), hypothetical purchasing, subjective effects (e.g., withdrawal, craving, and liking), and nicotine extraction from ST.

Methods: Twenty-eight male participants completed five sessions of prescribed ST use in a within-subjects, crossover design that included participants' usual-brand ST products and study ST products in which nicotine concentration was held constant and menthol levels were systematically varied: non-menthol, 1 mg of menthol per g of ST, 3 mg/g menthol, and 5 mg/g menthol.

Results: No significant differences in nicotine or cotinine PK, heart rate, hypothetical purchasing, or nicotine extraction were observed between products. Subjective ratings of "cooling" significantly differed between the non-menthol and mentholated study products, and higher ratings of cooling were associated with greater positive subjective effects.

Conclusions: These results suggest that menthol content up to 5 mg/g is unlikely to significantly impact nicotine absorption and may have a limited impact on the subjective experience of using ST.