The role of flavor in the substitutability of e-cigarettes for combustible cigarettes among persistent smokers

PROJECT SUMMARY
The average smoker will attempt to quit smoking at least 30 times before abstaining for 12 months or longer.
These attempts typically occur over decades of smoking, carcinogen and toxicant exposure, resulting in 480,000
deaths annually. As highlighted in the Surgeon General’s Report, helping smokers who cannot quit smoking
switch to less harmful non-combustible nicotine-containing products, such as e-cigarettes, has the potential to
reduce this health burden dramatically. Substituting e-cigarettes for combustible cigarettes might only be
possible for persistent smokers if e-cigarettes are accessible and appealing. Harm reduction proponents have
advocated for the continued availability of e-cigarette flavors to appeal to and aid cigarette smokers unable to
quit with traditional methods. Yet, there are no prospective studies of the effect of flavor on initial and
sustained switching from combustible to electronic cigarettes. Converging laboratory, epidemiological, and
clinical research suggests that fruit-flavored e-cigarettes with nicotine may be a viable substitute for combustible
cigarettes among persistent smokers. The proposed study seeks to answer two novel questions relevant to
public health and the regulation of e-cigarette flavoring. First, do persistent smokers substitute fruit-flavored e-
cigarettes more readily than traditional-flavored e-cigarettes (tobacco or menthol) for combustible cigarettes?
Second, are fruit-flavored e-cigarettes more rewarding and reinforcing than traditional-flavored e-cigarettes, and
do these effects facilitate switching? The proposed research will fill these gaps in the evidence base by
randomizing 210 persistent cigarette smokers to a six-week regimen of fruit-flavored (FF: watermelon and
blueberry, n=70), tobacco-flavored (TF n=70) or menthol-flavored (MF n=70) e-cigarettes in a between-subjects
design. Baseline smoking rate will be established during days 1-5. After biochemically verified overnight cigarette
smoking abstinence, laboratory visits on days 6 and 7 will assess flavor-associated subjective reward and the
reinforcing value of flavored e-cigarettes relative to combustible cigarettes. Participants will then switch from
cigarette smoking to e-cigarette use for six weeks. Participants will collect spent cigarette filters daily to assess
cigarettes smoked per day (cpd) if they smoke. The primary outcome measure is the longitudinal daily count of
cigarettes from baseline to the end of the six-week switch period, with cigarettes per day at a 6-month follow-up
as a secondary endpoint. This study aligns with NCI priorities outlined in the Notice of Special Interest
(NOSI NOT-OD-22-023) for research on “how ENDS use influences smoking (e.g., quit attempts,
sustained abstinence, relapse).”

Grant Number: 5R01CA287474-03
NIH Institute/Center: NIH
Principal Investigator: JANET AUDRAIN-MCGOVERN