An interventional study of E-liquid coolant (No WS-3) for non-menthol (1) and E-liquid coolant (No WS-3) for low (0.1%) menthol (1) in Nicotine Use Disorder, sponsored by Yale University. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-16.
Sponsored by Yale University · Not applicable, Interventional, and Other
This study is an examination of the influence of cooling components of WS-3, WS-23, and menthol on the appeal and addiction potential of nicotine-containing e-liquids among adults.
The investigators will examine the influence of cooling components of WS-3, WS-23 (synthetic coolants) and menthol on the appeal and addiction potential of nicotine-containing e-liquids among adults. Participants will rate the flavor intensity, coolness, sweetness, and irritation/harshness, bitterness experienced using validated rating scales. 66 adult participants (18+ years of age) who are current e-cigarette users will participate in 3 laboratory sessions. Participants will be randomized to receive one of the 3 menthol conditions (no-menthol, low menthol, high menthol) in Lab 1 and will receive the alternative conditions in randomized order in Lab 2 and Lab 3. During each lab session the menthol condition will be paired with three WS-3 concentrations: no WS-3, low (0.1%) WS-3, or high (2.0%) WS-3 and three WS-23 concentrations: low (0.1%) WS-23, high (2.0%) WS-23, or 4% WS-23 in randomized order. All e-cigarettes will contain nicotine salt at a nicotine concentration of \~59mg/ml and all participants will be exposed to eighteen conditions across 3 lab sessions.
Exclusion Criteria:
Flavor without menthol with 59mg/ml nicotine
Other: E-liquid coolant (No WS-3) for non-menthol (1)
Flavor with low menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (No WS-3) for low (0.1%) menthol (1)
Flavor with high menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (No WS-3) for high (2.0%) menthol (1)
Flavor without menthol with 59mg/ml nicotine
Other: E-liquid coolant (Low [0.1%] WS-3) for non-menthol (2)
Flavor with low menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (Low [0.1%] WS-3) for low (0.1%) menthol (2)
Flavor with high menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (Low [0.1%] WS-3) for high (2.0%) menthol (2)
Flavor without menthol with 59mg/ml nicotine
Other: E-liquid coolant (High [2.0%] WS-3) for non-menthol (3)
Flavor with low menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (High [2.0%] WS-3) for low (0.1%) menthol (3)
Flavor with high menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (High [2.0%] WS-3) for high (2.0%) menthol (3)
Flavor without menthol with 59mg/ml nicotine
Other: E-liquid coolant (Low [0.1%] WS-23) for non-menthol (4)
Flavor low menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (Low [0.1%] WS-23) for low (0.1%) menthol (4)
Flavor high menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (Low [0.1%] WS-23) for high (2.0%) menthol (4)
Flavor without menthol with 59mg/ml nicotine
Other: E-liquid coolant (High [2.0%] WS-23) for non-menthol (5)
Flavor low menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (High [2.0%] WS-23) for low (0.1%) menthol (5)
Flavor high menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (High [2.0%] WS-23) for high (2.0%) menthol (5)
Flavor without menthol with 59mg/ml nicotine
Other: E-liquid coolant (4% WS-23) for non-menthol (6)
Flavor low menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (4% WS-23) for low (0.1%) menthol (6)
Flavor high menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (4% WS-23) for high (2.0%) menthol (6)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-23 concentration.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-23 concentration.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-23 concentration.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-23 concentration.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-23 concentration.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-23 concentration.
Also known as: Flavor type
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with 4% WS-23 concentration.
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with 4% WS-23 concentration.
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with 4% WS-23 concentration.
Liking: Score change in liking/wanting of each e-cigarette condition (5 conditions in total)
The Labeled Hedonic Scale will be used to ask about liking and wanting of the e-cigarette (one item Visual Analog Scale with ratings ranging from "most disliked sensation imaginable" to "most liked sensation imaginable" with higher values indicating greater liking).
Time frame: Following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes)...following administration of e-cigarette condition 6 (at 160 minutes)
Reinforcing Efficacy: Score change in drug effects of each e-cigarette condition (5 conditions in total)
Difference between e-cigarette effects for each e-cigarette condition as measured by the computerized version of the Drug Effects Questionnaire (DEQ). Participants will self-report their responses using a computer mouse to indicate where on the scale response falls. A modified version of the Drug Effects Questionnaire (DEQ) will be used in which participants rate acute responses to the e-cigarette on a 0-100mm scale from "not at all" (0mm) to "extremely" (100mm).
Time frame: Following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes)...following administration of e-cigarette condition 6 (at 160 minutes)
Irritation/Harshness: Score change in irritation of harshness of each e-cigarette condition (5 conditions in total)
Difference in irritation at each e-cigarette condition as measured by the computerized Generalized Labeled Magnitude Scale (gLMS). Participants will self-report their responses using a computer mouse to indicate where on the scale response falls. The Generalized Labeled Magnitude Scales (gLMS) are category ratio scales with seven semantic labels: "no sensation", "barely detectable", "weak", "moderate", "strong", "very strong", and "strongest imaginable", positioned quasi-logarithmically as per empirically determined semantic magnitudes on a 0-100 scale (strongest imaginable at the 100 end).
Time frame: Following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes)...following administration of e-cigarette condition 6 (at 160 minutes)
Craving: Change in craving score for e-cigarette from baseline at each e-cigarette condition (5 conditions in total)
Difference from baseline in craving for each e-cigarette condition will be measured by the Generalized Labeled Magnitude Scale (gLMS). Participants will self-report their craving for e cigarettes using a computer mouse to indicate where on the scale response falls. The Generalized Labeled Magnitude Scales (gLMS) are category ratio scales with seven semantic labels: "no sensation", "barely detectable", "weak", "moderate", "strong", "very strong", and "strongest imaginable", positioned quasi-logarithmically as per empirically determined semantic magnitudes on a 0-100 scale (strongest imaginable at the 100 end).
Time frame: At baseline (at 0 minute), following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes)...following administration of e-cigarette condition 6 (at 160 minutes)
Changes of salivary Nicotine and Cotinine Levels from baseline at each e-cigarette condition (6 conditions in total)
Saliva samples will be collected following each exposure to product and before each lab sessions to assess change in nicotine/cotinine levels. These levels will be used for correlational analyses with behavioral measures and will be determined using LC/MS techniques at the core laboratory of university.
Time frame: At baseline (at 0 minute), Following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes)...following administration of e-cigarette condition 6 (at 160 minutes)
Plan to share: Yes — We may share information about the IPD and study results with other researchers in the future, but the information will be de-identified.
Supporting information: Study protocol, Analytic code
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