# Examining Appeal and Addiction Potential of Novel e-Cigarette Constituents

> **NIH NIH U54** · YALE UNIVERSITY · 2024 · $340,555

## Abstract

Project Summary/Abstract
The appeal and addiction potential of e-cigarettes (e-cigs) is influenced by constituents like nicotine (the
primary reinforcer that produces sensory irritation) and cooling flavorants (which improve flavor and can reduce
irritation). The tobacco marketplace is constantly introducing “disruptive innovations” in e-cigs, which may
impact appeal and addiction potential. Two recent entrants into the marketplace that are widely available in e-
cigs are the synthetic coolant WS-3 and synthetic nicotine, manufactured in the lab and is not from the tobacco
plant. The FDA has regulatory authority over these constituents, but little is known about their impact. This
proposal will use established human e-cig exposure models to conduct the first studies comparing synthetic
WS-3 vs. traditional coolants (i.e. menthol) and synthetic nicotine vs. tobacco-derived among those who use e-
cigs, to get consistent and reliable reports on user experiences.
Aim 1 will characterize user experiences to nicotine e-liquids with the synthetic coolant WS-3 alone, when
combined with menthol, and in comparison to menthol alone. After pilot testing to determine optimal WS-
3/menthol concentrations, adult users of e-cigs (50% with combustible tobacco use) will be exposed to three
WS-3 concentrations (no WS-3, low, high) in combination with three menthol concentrations (no menthol, low,
high; 9 total exposures) in a nicotine containing e-cig. Addiction potential and appeal will be examined with
hypothesized similar increases in additional potential/appeal for menthol and WS-3 and additive effects when
combined. Secondary and exploratory analyses with examine interactive effects of WS-3 and menthol and
influence of predictors (e.g. age, sex, combustible tobacco use, nicotine dependence) on outcomes. Aim 2 will
characterize user experiences to nicotine e-liquids with synthetic nicotine and menthol. In separate lab
sessions, adult users of e-cigs (50% with combustible tobacco use) will be exposed to synthetic nicotine in
tobacco and menthol flavor and tobacco derived nicotine in tobacco and menthol flavor in nicotine containing
e-cigs. Addiction potential and appeal will be examined across conditions and repeated exposure to each
condition will be used to examine withdrawal effects. We hypothesize synthetic nicotine will have greater
appeal and addiction potential than tobacco-derived nicotine. Secondary and exploratory effects will examine
the flavor and nicotine form interactions and influence of predictors (e.g. age, sex, combustible tobacco use,
nicotine dependence) on outcomes. These pivotal and rigorous experiments will inform future research and
regulatory needs to balance the impact of these synthetic constituents on initiation and harm reduction.

## Key facts

- **NIH application ID:** 10934553
- **Project number:** 5U54DA036151-12
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** SUCHITRA KRISHNAN-SARIN
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $340,555
- **Award type:** 5
- **Project period:** 2013-09-30 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10934553

## Citation

> US National Institutes of Health, RePORTER application 10934553, Examining Appeal and Addiction Potential of Novel e-Cigarette Constituents (5U54DA036151-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10934553. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*