Effects of Novel E-cigarette Constituents on Adults TCORS 3.0

This study is an examination of the influence of cooling components of WS-3 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 (a synthetic coolant) 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 receive 3 e-cigarette that contain cooling flavors and nicotine (59mg/ml nicotine salt) during the sessions. Participants will be randomized to receive one of the 3 menthol conditions (no-menthol, low menthol, high menthol) in combination three WS-3 conditions (no WS-3, low WS-3, high WS-3). All participants will be exposed to all nine conditions across 3 lab sessions.

Participants will be given a nicotine containing e-cigarette that could have various levels of cooling flavoring. Participants will not be told the nicotine concentration of the product or the type or concentration of the added coolant or what order it is presented in. Investigator and research assistant (i.e. care provider) will know the doses of nicotine and coolant, but will not know what order coolants are presented to participants.

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.

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 3 (at 70 minutes)

Reinforcing Efficacy: Score change in drug effects of each e-cigarette condition (3 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 3 (at 70 minutes)

Irritation/Harshness: Score change in irritation of harshness of each e-cigarette condition (3 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 3 (at 70 minutes)

Craving: Change in craving score for e-cigarette from baseline at each e-cigarette condition (3 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 3 (at 70 minutes)

Changes of salivary Nicotine and Cotinine Levels from baseline at each e-cigarette condition (3 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 3 (at 70 minutes)

Inclusion Criteria: 18 years or older Able to read and write Some current e-cigarette use 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

We may share information about the IPD and study results with other researchers in the future, but the information will be de-identified.

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.