# Beyond characterizing flavors: Effects of odorless constituents (sensory additives, solvents, and synthetic nicotine) on tobacco product use behaviors from adolescence to adulthood

> **NIH NIH U54** · YALE UNIVERSITY · 2024 · $648,571

## Abstract

Project Summary/Abstract:
Characterizing flavors in tobacco products are associated with increased tobacco use initiation, reinforcement,
and difficulty quitting. In addition to characterizing flavors, tobacco products contain odorless sensory additives
such as sweeteners and synthetic cooling agents found in e-cigarettes and smokeless tobacco products.
Because these chemicals are odorless, they may not be considered characterizing flavors under current FDA
definitions and may continue to be added to tobacco products even when characterizing flavors are banned.
Solvent/humectant composition of e-cigarettes and smokeless tobacco, with different combinations of propylene
glycol and glycerol, and different levels of irritancy and sweetness, may also affect product perceptions.
Moreover, certain forms of recently introduced synthetic nicotine may also affect the sensory properties of
tobacco products and alter nicotine use behaviors. The effects of these odorless constituents (sweeteners,
synthetic cooling agents, solvents, and synthetic nicotine) on youth and adult tobacco product use, especially in
the critical context of transition from intermittent adolescent use to persistent adult tobacco use, remain poorly
understood. We propose to determine how these odorless constituents alter the sensory and addictive
properties of nicotine at different ages, and how early intermittent exposure to products containing these
constituents alters nicotine use behaviors in adulthood. Specifically, we will assess the effects of odorless
constituents on sensory and addictive properties of nicotine in adolescent and adult rodents (Aim 1). We will use
rodent taste reactivity and respiratory exposure assays to determine whether sweeteners, cooling agents, and
solvents modulate oral and respiratory sensory responses to tobacco-derived and synthetic nicotine
stereoisomers. We will also examine the effects of synthetic cooling agents on nicotine use behaviors (initiation,
maintenance, withdrawal, reinstatement) and nicotine-induced dopamine release in brain (brain reward system).
We will evaluate interactive effects of cooling agents, solvent ratios, and nicotine enantiomers on nicotine use
behaviors using operant vapor self-administration. In addition, we will examine how intermittent exposure to
odorless constituents in vapor or oral nicotine in adolescent rodents affects nicotine use behaviors in adulthood
(Aim 2). We will use a mixed vapor passive exposure and self-administration model as well as choice drinking
assays to evaluate and compare the effects of intermittent exposure and preconditioning to sweetener and
synthetic coolants or characterizing flavors during adolescence. We will determine whether exposure to these
additives alters adult nicotine seeking, dependence, reward-related behaviors, and brain dopamine release later
in life. Our findings will also evaluate the role of sex and age in the effects of odorless constituents on tobacco
use. Project outcome...

## Key facts

- **NIH application ID:** 10934549
- **Project number:** 5U54DA036151-12
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Nii A Addy
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $648,571
- **Award type:** 5
- **Project period:** 2013-09-30 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10934549

## Citation

> US National Institutes of Health, RePORTER application 10934549, Beyond characterizing flavors: Effects of odorless constituents (sensory additives, solvents, and synthetic nicotine) on tobacco product use behaviors from adolescence to adulthood (5U54DA036151-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10934549. Licensed CC0.

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