Testing the Effect of ENDS Flavors on Neurotransmission (TEN)

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.

Study Overview

• Status: Completed
• Conditions: Tobacco Dependence
• Intervention / Treatment: Other: Flavor

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Actual): May 30, 2025
• Study Completion (Actual): July 31, 2025

Study Registration Dates

• First Submitted: April 18, 2023
• First Submitted That Met QC Criteria: April 18, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Smoking; Tobacco; Addiction; Nicotine
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Compulsive Behavior; Impulsive Behavior; Behavior; Tobacco Use Disorder; Behavior, Addictive; Smoking; Pharmaceutical Preparations; Chemical Actions and Uses; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Specialty Uses of Chemicals; Pharmaceutic Aids; Food Additives; Food Ingredients; Flavoring Agents
• Other Study ID Numbers: 19883; 24844; R61DA056764 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No