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OpenTrials
Completed

NCT Number: NCT05836051

Testing the Effect of ENDS Flavors on Neurotransmission

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.

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Key information

Age range

21 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Penn State Health

Hershey, Pennsylvania, 17033, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 21 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

Exclusion criteria

  • 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-specific exclusion criteria:

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

Treatment and study plan

Flavor

Other

E-liquid flavor chemicals

Primary outcomes

  1. Brain reward reactivity

    Time frame: Pre to post-intervention (approximately 10 days)

    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

  2. Absolute reinforcement

    Time frame: Pre to post-intervention (approximately 10 days)

    Absolute reinforcement will be calculated as the change in the average number of puffs per day during a 10-day use period

Sponsors and collaborators

Lead sponsor

Milton S. Hershey Medical Center

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)

Registry information

Acronym: TEN

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
May 1, 2023
Registry last updated
Sep 25, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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