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
Received: 21 March 2017 /Accepted: 19 May 2017 / Published online: 20 June 2017
The Author(s) 2017. This article is an open access publication
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 ciga-
rettes and nicotine gum, respectively) in a group of 45 EC-
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 nic-
otine 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 sub-
stantially faster and higher levels of nicotine uptake as com-
pared 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:
Keywords Abuse liability
A growing body of evidence supports the contention that elec-
tronic cigarettes (ECs) are a substantially less harmful alterna-
tive to combustible cigarettes for smokers (Caponnetto et al.
2012; Etter and Bullen 2013; Goniewicz et al. 2014;
Farsalinos and Polosa 2014; Hajek et al. 2014; Hecht et al.
2015; McNeill et al. 2015; Truth Initiative 2015;Rassetal.
2015). Research suggests the existence of a pronounced Bcon-
tinuum of risk^ of tobacco and nicotine products (Kozlowski
et al. 2001; Zeller and Hatsukami 2009;O’Connor 2012;
Hatsukami 2013;Nuttetal.2014; U. S. Department of
Health and Human Services 2014;Rassetal.2015). At one
end of the continuum, cigarette smoking poses the most sig-
nificant risk of serious diseases. At the other end of the con-
tinuum, medicinal nicotine replacement therapies provide pri-
marily nicotine and carry a very low risk of abuse, addiction,
and harm (Murray et al. 1996; Waldum et al. 1996;Benowitz
2012; U. S. Department of Health and Human Services 2014).
Similarly, nicotine-delivering products and dosage forms vary
Electronic supplementary material The online version of this article
(doi:10.1007/s00213-017-4665-y) contains supplementary material,
which is available to authorized users.
* Mitchell F. Stiles
RAI Services Company, 401 N. Main Street,
Winston-Salem, NC 27101, USA
Celerion, Lincoln, NE, USA
Pinney Associates, Inc., Bethesda, MD, USA
Psychopharmacology (2017) 234:2643–2655