The overarching goal of this translational proposal is to determine if neuroactive flavor chemicals can enhance the addiction potential of electronic nicotine delivery systems (ENDS) by altering brain function and behavior.

For this randomized double-blind controlled trial, tobacco users will be randomized to use ENDS with an e-liquid containing a neuroactive flavor (hexyl acetate) vs. an inactive flavor (ethyl acetate) for ten days as a supplement to their typical tobacco use. Laboratory measures of ENDS reinforcement, subjective ENDS ratings, and brain reactivity to the flavor using functional magnetic resonance imaging (fMRI) will be collected at baseline and after ten days of ENDS use.

Inclusion Criteria:

1. 21 to 60 years old
2. Regular users of inhaled tobacco products (≥5 days out of the last 28)
3. Not planning to quit tobacco use within next month
4. Able to read and write in English

Exclusion Criteria:

1. Major neurological conditions or brain trauma
2. Current substance use impairing participation
3. Unstable or significant medical conditions (e.g., COPD, coronary heart disease)
4. Current use of smoking cessation medication (e.g., varenicline, patch)
5. Uncontrolled serious mental illness, suicidality, or inpatient psychiatric hospitalization in the past 6 months
6. Known allergic reaction to ENDS liquids ingredients propylene glycol or vegetable glycerin
7. Unable to use study provided ENDS ad-libitum for at least 3 hours per day
8. Pregnant or breastfeeding as indicated by self-report or urine pregnancy screen

MRI-specific exclusion criteria:

1. MRI safety contraindications (e.g., metal implants, claustrophobia)
2. Major neurological conditions or brain trauma

We do not have explicit plans to share IPD on open-access or publicly accessible repositories. However, IPD will be de-identified and formatted along with codebooks to facilitate data sharing with investigators upon request and after the completion of a Data Use Agreement.