# E-liquid flavor alters nicotine exposure, puff topography, and subjective effects under ad libitum use conditions

## TL;DR

This study found that e-liquids with tobacco flavor result in lower nicotine exposure and less liking compared to fruit or menthol flavors, which may make them less addictive.

## Contribution

The study is the first to compare abuse liability of tobacco, fruit, and menthol e-liquids under ad libitum use conditions.

## Key findings

- Tobacco-flavored e-liquids led to lower plasma nicotine levels and fewer puffs compared to other flavors.
- Zero-nicotine fruit e-liquids did not reduce withdrawal symptoms and were associated with greater puff duration.
- Tobacco flavor was rated lower on liking and may have lower abuse liability than non-tobacco flavors.

## Abstract

•Tobacco flavor had lower liking and nicotine exposure than other e-liquids.•Tobacco flavor eased withdrawal less than menthol or fruit flavor e-liquids.•A zero-nicotine fruit e-liquid did not ease withdrawal symptoms.•Tobacco flavor e-liquids may have lower abuse liability than non-tobacco flavors.•E-liquids with lower liking and nicotine exposure may substitute for cigarettes.

Tobacco flavor had lower liking and nicotine exposure than other e-liquids.

Tobacco flavor eased withdrawal less than menthol or fruit flavor e-liquids.

A zero-nicotine fruit e-liquid did not ease withdrawal symptoms.

Tobacco flavor e-liquids may have lower abuse liability than non-tobacco flavors.

E-liquids with lower liking and nicotine exposure may substitute for cigarettes.

Electronic nicotine delivery systems (ENDS) are most often used with e-liquids having fruit, and menthol or mint flavor, with tobacco flavor being least prevalent. This study evaluated the effect of a tobacco, fruit, and menthol e-liquid flavor on ENDS abuse liability.

Fifty-two regular ENDS users participated in a double-blinded, randomized, crossover-design study. Study conditions were ENDS (KangerTech CUPTI) with tobacco, menthol, or fruit flavor e-liquids with 1.2 % (all flavors) or 0 % (fruit only) freebase nicotine concentration. On separate days participants used the study products for 10 prescribed puffs and 1 h of ad libitum use. Plasma nicotine concentration, puff topography, and subjective effects were measured.

Following ad libitum use, tobacco flavor ENDS were associated with significantly lower plasma nicotine levels than other nicotine-containing ENDS. Significantly fewer puffs were taken from the tobacco flavor ENDS than other products, and the 0% nicotine fruit flavor ENDS was associated with greater puff duration and puff volumes than other products. Tobacco flavor was rated significantly lower than other flavors on product liking (e.g., “tastes good” or “pleasant”), while only the 0% nicotine fruit flavor ENDS was associated with significantly greater withdrawal symptoms (e.g., ENDS craving, or urge to use an ENDS) compared to the other flavors.

Tobacco flavor ENDS were rated lower on liking, and associated with less nicotine exposure and fewer puffs taken, but comparably attenuated withdrawal symptoms to other flavor ENDS, while the non-nicotine fruit flavor did not affect withdrawal symptoms.