Effects of Novel E-cigarette Constituents on Adults TCORS 3.0

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

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.

Study Overview

• Status: Recruiting
• Conditions: Nicotine Use Disorder
• Intervention / Treatment: Other: E-liquid coolant (No WS-3) for non-menthol (1); Other: E-liquid coolant (No WS-3) for low (0.1%) menthol (1); Other: E-liquid coolant (No WS-3) for high (2.0%) menthol (1); Other: E-liquid coolant (Low [0.1%] WS-3) for non-menthol (2); Other: E-liquid coolant (Low [0.1%] WS-3) for low (0.1%) menthol (2); Other: E-liquid coolant (Low [0.1%] WS-3) for high (2.0%) menthol (2); Other: E-liquid coolant (High [2.0%] WS-3) for non-menthol (3); Other: E-liquid coolant (High [2.0%] WS-3) for low (0.1%) menthol (3); Other: E-liquid coolant (High [2.0%] WS-3) for high (2.0%) menthol (3); Other: E-liquid coolant (Low [0.1%] WS-23) for non-menthol (4); Other: E-liquid coolant (Low [0.1%] WS-23) for low (0.1%) menthol (4); Other: E-liquid coolant (Low [0.1%] WS-23) for high (2.0%) menthol (4); Other: E-liquid coolant (High [2.0%] WS-23) for non-menthol (5); Other: E-liquid coolant (High [2.0%] WS-23) for low (0.1%) menthol (5); Other: E-liquid coolant (High [2.0%] WS-23) for high (2.0%) menthol (5); Other: E-liquid coolant (4% WS-23) for non-menthol (6); Other: E-liquid coolant (4% WS-23) for low (0.1%) menthol (6); Other: E-liquid coolant (4% WS-23) for high (2.0%) menthol (6)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Danielle Davis, PhD; Phone Number: 203-974-7607; Email: danielle.davis@yale.edu
• Study Contact Backup: Name: Wei Li, PhD; Email: wei.vanness.li@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • JB Pierce Lab

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

18

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Non-menthol, nicotine 59mg/ml (1); Flavor without menthol with 59mg/ml nicotine	Other: E-liquid coolant (No WS-3) for non-menthol (1); Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.; Other Names: Flavor type
Experimental: Non-menthol, nicotine 59mg/ml (2); Flavor without menthol with 59mg/ml nicotine	Other: E-liquid coolant (Low [0.1%] WS-3) for non-menthol (2); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.; Other Names: Flavor type
Experimental: Non-menthol, nicotine 59mg/ml (3); Flavor without menthol with 59mg/ml nicotine	Other: E-liquid coolant (High [2.0%] WS-3) for non-menthol (3); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.; Other Names: Flavor type
Experimental: Non-menthol, nicotine 59mg/ml (4); Flavor without menthol with 59mg/ml nicotine	Other: E-liquid coolant (Low [0.1%] WS-23) for non-menthol (4); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-23 concentration.; Other Names: Flavor type
Experimental: Non-menthol, nicotine 59mg/ml (5); Flavor without menthol with 59mg/ml nicotine	Other: E-liquid coolant (High [2.0%] WS-23) for non-menthol (5); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-23 concentration.; Other Names: Flavor type
Experimental: Low (0.1%) menthol, nicotine 59mg/ml (1); Flavor with low menthol concentration with 59mg/ml nicotine	Other: E-liquid coolant (No WS-3) for low (0.1%) menthol (1); Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.; Other Names: Flavor type
Experimental: High (2.0%) menthol, nicotine 59mg/ml (1); Flavor with high menthol concentration with 59mg/ml nicotine	Other: E-liquid coolant (No WS-3) for high (2.0%) menthol (1); Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.; Other Names: Flavor type
Experimental: Low (0.1%) menthol, nicotine 59mg/ml (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); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.; Other Names: Flavor type
Experimental: High (2.0%) menthol, nicotine 59mg/ml (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); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.; Other Names: Flavor type
Experimental: Low (0.1%) menthol, nicotine 59mg/ml (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); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.; Other Names: Flavor type
Experimental: High (2.0%) menthol, nicotine 59mg/ml (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); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.; Other Names: Flavor type
Experimental: Low (0.1%) menthol, nicotine 59mg/ml (4); Flavor low menthol concentration with 59mg/ml nicotine	Other: E-liquid coolant (Low [0.1%] WS-23) for low (0.1%) menthol (4); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-23 concentration.; Other Names: Flavor type
Experimental: High (2.0%) menthol, nicotine 59mg/ml (4); Flavor high menthol concentration with 59mg/ml nicotine	Other: E-liquid coolant (Low [0.1%] WS-23) for high (2.0%) menthol (4); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-23 concentration.; Other Names: Flavor type
Experimental: Low (0.1%) menthol, nicotine 59mg/ml (5); Flavor low menthol concentration with 59mg/ml nicotine	Other: E-liquid coolant (High [2.0%] WS-23) for low (0.1%) menthol (5); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-23 concentration.; Other Names: Flavor type
Experimental: High (2.0%) menthol, nicotine 59mg/ml (5); Flavor high menthol concentration with 59mg/ml nicotine	Other: E-liquid coolant (High [2.0%] WS-23) for high (2.0%) menthol (5); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-23 concentration.; Other Names: Flavor type
Experimental: Non-menthol, nicotine 59mg/ml (6); Flavor without menthol with 59mg/ml nicotine	Other: E-liquid coolant (4% WS-23) for non-menthol (6); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with 4% WS-23 concentration.
Experimental: Low (0.1%) menthol, nicotine 59mg/ml (6); Flavor low menthol concentration with 59mg/ml nicotine	Other: E-liquid coolant (4% WS-23) for low (0.1%) menthol (6); Adult users of e-cigarette will be exposed to distinct e-liquid coolants with 4% WS-23 concentration.
Experimental: High (2.0%) menthol, nicotine 59mg/ml (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 with 4% WS-23 concentration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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).	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).	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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)

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Suchitra Krishnan-Sarin, PhD, Yale University

Publications and helpful links

General Publications

• Lim J, Wood A, Green BG. Derivation and evaluation of a labeled hedonic scale. Chem Senses. 2009 Nov;34(9):739-51. doi: 10.1093/chemse/bjp054.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: June 28, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): December 26, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Menthol, cooling components, cigarette, e-cigarette, vaping
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Behavior; Smoking; Tobacco Use Disorder; Vaping; Organic Chemicals; Lipids; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Alcohols; Cyclohexanols; Hexanols; Fatty Alcohols; Cyclohexane Monoterpenes; Monoterpenes; Menthol
• Other Study ID Numbers: 2000035551_b; 2U54DA036151-11 (U.S. NIH Grant/Contract: NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We may share information about the IPD and study results with other researchers in the future, but the information will be de-identified.
• IPD Sharing Time Frame: The identifiable information will be kept for 7 years. After that, the data will become anonymous.
• IPD Sharing Access Criteria: The de-identified data will be made available for research purposes by contacting the PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

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