How cooling ingredients and menthol change the feel of nicotine e-liquids for adult vapers

Examining Appeal and Addiction Potential of Novel E-cigarette Constituents Among Adults

Not applicable Interventional Yale University · NCT05932745

This project will test whether cooling chemicals (WS-3, WS-23) and menthol make nicotine e-liquids more appealing or habit-forming for adults who use e-cigarettes.

Quick facts

PhaseNot applicable
Study typeInterventional
Enrollment66 (estimated)
Ages18 Years and up
SexAll
SponsorYale University Academic / other
Locations1 site (New Haven, Connecticut)
Trial IDNCT05932745 on ClinicalTrials.gov

What this trial studies

Sixty-six adults who currently use e-cigarettes will attend three in-person lab sessions and be exposed to a total of 18 different e-liquid conditions containing nicotine salt (~59 mg/ml). Participants are randomized to one of three menthol conditions across sessions (no menthol, low, high) and, within each session, sample combinations of WS-3 and WS-23 at varying concentrations in randomized order. During each exposure, participants will rate flavor intensity, coolness, sweetness, irritation/harshness, and bitterness using validated scales. The study uses strict eligibility (e.g., urine cotinine ≥200 ng/ml) and brief pre-session abstinence to ensure participants are current e-cigarette users.

Who should consider this trial

Good fit: Ideal candidates are adults (18+) who are current e-cigarette users with urine cotinine ≥200 ng/ml, willing to abstain from nicotine for two hours and to attend three lab visits in New Haven, CT.

Not a fit: People who do not vape, are pregnant or breastfeeding, have uncontrolled asthma, allergies to propylene glycol or flavorants, current nonprescription substance use (aside from allowed substances), or who dislike menthol are excluded and unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could help regulators and clinicians understand which cooling agents increase appeal or addiction risk and guide policies or advice to reduce harm.

How similar studies have performed: Prior work shows menthol can increase appeal and alter sensory perception linked to dependence, while synthetic coolants like WS-3 and WS-23 are less well-studied, so this study is partly confirmatory and partly novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* 18 years or older
* Able to read and write
* Some current e-cigarette use
* Urine cotinine ≥200ng/ml
* Willing to abstain from tobacco/nicotine use 2 hours prior to sessions

Exclusion Criteria:

* Current use of non-prescription substances besides nicotine, marijuana, alcohol
* Any significant current medical or psychiatric condition
* Known hypersensitivity to propylene glycol
* Pregnant or lactating females
* Uncontrolled asthma
* Nut/e-liquid flavorant allergy
* Current marijuana (tetrahydrocannabinol) vaping + E-cigarette or vaping use Associated Lung Injury (EVALI) symptoms
* Dislike of menthol flavor

Where this trial is running

New Haven, Connecticut

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Nicotine Use DisorderMenthol, cooling components, cigarette, e-cigarette, vaping
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.