Testing the Effect of ENDS Flavors on Neurotransmission

Study Overview
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Brief Summary
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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.

Detailed Description
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For this randomized double-blind controlled trial, tobacco users will be randomized to use ENDS with an e-liquid containing a neuroactive green-apple flavor (hexyl acetate) vs. an inactive green-apple 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.

Official Title
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Testing the Effect of ENDS Flavors on Neurotransmission

Conditions
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Tobacco Dependence

Intervention / Treatment
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* Other: Flavor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 21 years old or older Weekly user of inhaled tobacco products, including inhaled ENDS, nicotine vapes, cigarettes, regular and little cigars for at least last three months Not planning to quit tobacco use within next month Able to read and write in English Exclusion Criteria: Current substance use impairing participation Unstable or significant medical conditions (e.g., COPD, coronary heart disease) Current use of smoking cessation medication (e.g., varenicline, patch) Uncontrolled serious mental illness, suicidality, or inpatient psychiatric hospitalization in the past 6 months Unable or unwilling to abstain from nicotine products for 14 hours prior to the scheduled visit, self-reported. MRI-specific exclusion criteria: MRI safety contraindications (e.g., metal implants, claustrophobia) Major neurological conditions or brain trauma

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hexyl Acetate<br>E-cigarette liquid containing hexyl acetate, propylene glycol, vegetable glycerin and methylbutyl acetate with nicotine salt. | Other: Flavor<br>* E-liquid flavor chemicals<br>|
| Active Comparator: Ethyl Acetate<br>E-cigarette liquid containing ethyl acetate, propylene glycol, vegetable glycerin and methylbutyl acetate with nicotine salt. | Other: Flavor<br>* E-liquid flavor chemicals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain reward reactivity | Brain reward reactivity will be calculated as the percent change in average blood oxygen-level dependent (BOLD) signal in a pre-defined ventral tegmental area (VTA) region of interest during ENDS inhalation | Pre to post-intervention (approximately 10 days) | 
| Absolute reinforcement | Absolute reinforcement will be calculated as the change in the average number of puffs per day during a 10-day use period | Pre to post-intervention (approximately 10 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tobacco, Nicotine, Smoking, Addiction