Testing the Effect of ENDS Flavors on Neurotransmission

NCT05836051 | Completed

• 2 other identifiers: 19883; 24844R61DA056764
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tobacco Dependence

Keywords

Tobacco; Nicotine; Smoking; Addiction

Outcome Measures

Primary Outcomes (2)

• 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)

Study Arms (2)

Hexyl Acetate

EXPERIMENTAL

E-cigarette liquid containing hexyl acetate, ethyl maltol, propylene glycol, vegetable glycerin and methylbutyl acetate with nicotine salt.

Other: Flavor

Ethyl Acetate

ACTIVE COMPARATOR

E-cigarette liquid containing ethyl acetate, ethyl maltol, propylene glycol, vegetable glycerin and methylbutyl acetate with nicotine salt.

Other: Flavor

Interventions

Flavor OTHER

E-liquid flavor chemicals

Ethyl Acetate; Hexyl Acetate

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Major neurological conditions or brain trauma
• 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
• Known allergic reaction to ENDS liquids ingredients propylene glycol or vegetable glycerin
• Unable to use study provided ENDS ad-libitum for at least 3 hours per day
• Pregnant or breastfeeding as indicated by self-report or urine pregnancy screen
• MRI safety contraindications (e.g., metal implants, claustrophobia)
• Major neurological conditions or brain trauma

Sponsors & Collaborators

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

Study Sites (1)

Penn State Health

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking; Behavior, Addictive

Interventions

Flavoring Agents

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavior; Compulsive Behavior; Impulsive Behavior

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Food Additives; Food Ingredients; Specialty Uses of Chemicals; Chemical Actions and Uses; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 18, 2023
• First Posted: May 1, 2023
• Study Start: June 1, 2023
• Primary Completion: May 30, 2025
• Study Completion: July 31, 2025
• Last Updated: September 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)