Pharmacodynamic and pharmacokinetic assessment of electronic cigarettes, combustible cigarettes, and nicotine gum: implications for abuse liability

Mitchell F Stiles, Leanne R Campbell, Donald W Graff, Bobbette A Jones, Reginald V Fant, Jack E Henningfield, Mitchell F Stiles, Leanne R Campbell, Donald W Graff, Bobbette A Jones, Reginald V Fant, Jack E Henningfield

Abstract

Rationale: Electronic cigarettes (ECs) are becoming popular alternatives for smokers, but there has been limited study of their abuse liability.

Objectives: The objective of this study was to evaluate the abuse liability of three Vuse Solo ECs, ranging from 14 to 36 mg in nicotine content, relative to high- and low-abuse liability comparator products (usual brand combustible cigarettes and nicotine gum, respectively) in a group of 45 EC-naïve smokers.

Methods: Enrolled subjects' ratings of subjective effects and nicotine uptake over 6 h were used to measure abuse liability and pharmacokinetics following in-clinic use of each EC.

Results: Use of Vuse Solo resulted in subjective measures and nicotine uptake that were between those of combustible cigarettes and nicotine gum, although generally closer to nicotine gum. Compared to combustible cigarettes, use of Vuse Solo resulted in significantly lower scores in measures of product liking, positive effects, and intent to use again. These pharmacodynamic findings were consistent with the pharmacokinetic data, showing that cigarettes produced substantially faster and higher levels of nicotine uptake as compared to Vuse Solo and nicotine gum. Vuse Solo resulted in more rapid initial uptake of nicotine compared to nicotine gum, but peak concentration and long-term extent of uptake were not different or were lower with Vuse.

Conclusions: Collectively, these findings suggest that Vuse Solo likely has an abuse liability that is somewhat greater than nicotine gum but lower than cigarettes.

Trial registration: ClinicalTrials.gov identifier: NCT02269514.

Keywords: Abuse liability; Electronic cigarettes; Nicotine pharmacokinetics; Pharmacodynamics; Product liking; Subjective measures.

Conflict of interest statement

Funding

This study was funded by RJ Reynolds Vapor Company through its affiliate RJ Reynolds Tobacco Company.

Conflict of interest

MF Stiles, LR Campbell, and BA Jones are full-time employees of RAI Services Company, which provides support across the Reynolds American Inc. operating companies. DW Graff is a full-time employee of Celerion and provided the original draft of this manuscript. RV Fant and JE Henningfield are full-time employees of PinneyAssociates, which provides consulting services on tobacco harm minimization (including nicotine replacement therapy and digital vapor products) to Niconovum USA, RJ Reynolds Vapor Company, and RAI Services Company (all subsidiaries of Reynolds American Inc.) In the past 3 years, PinneyAssociates has consulted to GlaxoSmithKline Consumer Healthcare on smoking cessation and NJOY on electronic cigarettes. JE Henningfield also owns an interest in intellectual property for a novel nicotine medication, an option for which has been sold to Niconovum USA. Through PinneyAssociates, Fant and Henningfield also provide consulting services to pharmaceutical companies on abuse potential assessment and the regulation of substances with a potential for abuse.

Figures

Fig. 1
Fig. 1
Mean ratings for the urge to smoke question “How strong is your current urge to smoke your usual brand cigarette?”
Fig. 2
Fig. 2
Mean plasma nicotine concentration profiles

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