Assess the Influence of Nicotine Flux and Nicotine Form on Subjective Effects Related to Dependency

American University of Beirut Medical Center

Status: Completed

Conditions: Nicotine Dependence; Nicotine Addiction; Nicotine Vaping

Treatments: Combination Product: e-liquid 4; Combination Product: e-liquid 6; Combination Product: e-liquid 3; Combination Product: e-liquid 7 and e-liquid 8; Combination Product: e-liquid 9 and e-liquid 10; Combination Product: e-liquid 5; Combination Product: e-liquid 2; Combination Product: e-liquid 1

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05430334

American University Of Beirut

1R01DA052565-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Electronic nicotine delivery systems (ENDS) heat and vaporize a nicotine-containing liquid to produce an aerosol that can deliver nicotine to the blood and the brain. ENDS use has increased rapidly in the last decade, especially among youth: over 20% of US high school students are current ENDS users, and there is evidence of nicotine dependence in this population. Federal legislation has been proposed that would restrict ENDS liquid nicotine concentration to make ENDS "significantly less addictive and appealing to youth." However, these and other efforts to curb addiction by limiting nicotine liquid concentration are unlikely to succeed because nicotine emissions from ENDS depend on multiple variables. To achieve the intended public health aims, regulations targeting addiction must focus on nicotine delivery, not nicotine concentration. While nicotine delivery cannot be regulated directly, the rate at which an ENDS emits nicotine, the "nicotine flux", can be regulated and, importantly, predicted based on a few device design and operating variables. However, to date there is no empirical evidence demonstrating the relationship between flux and delivery, nor between flux and the subjective effects that support nicotine dependence. Closing this gap is essential for providing an effective framework for regulating ENDS. At the American University of Beirut, the investigators will assess the relationship between nicotine flux, form, and subjective effects. Participants will use ENDS devices with varying nicotine fluxes and forms. Dependency measures, such as urge to smoke, craving, and abstinence, will be assessed. The outcome will indicate the degree to which nicotine flux/form influence subjective effects related to dependency, puffing intensity, and exposure to toxicants. In summary, this project will provide the empirical evidence needed for public health agencies to use nicotine flux as an encompassing and convenient construct to regulate nicotine delivery from ENDS.

Full description

Assess the influence of nicotine flux and nicotine form on subjective effects. At AUB, the investigators will assess subjective effects (e.g. product liking, nicotine craving) and puffing topography for 130 participants who will undergo 5 ENDS use sessions (combinations 1-5) consisting of 2 bouts (10 puffs + 60min ad libitum) with 2 fluxes (16 and 32μg/s) x 2 forms (protonated, freebase) and a 0 nicotine condition. In addition, the investigators will use a state-of-the-art device to sample in situ a fraction of the aerosol generated during each puff to verify actual nicotine flux and form, and measure exposure to pulmonary toxicants (carbonyls). The investigators hypothesize that increasing nicotine flux and protonated nicotine will result in greater reductions of nicotine craving, and lower puffing intensity and carbonyl exposure. In addition, 10 participants that completed the five use sessions will attend the lab for one additional visit with the aim of determining the influence of puff-by-puff variation of ENDS power and liquid composition on puffing behavior and sensory effects. During this visit participants will complete three directed puffing bouts (10 puffs). In each bout, participants will alternate puffs between two identical ENDS devices differing by a single design factor (combinations 6-8).

Enrollment: 130 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Must be healthy and above 18 years of age
• Must be willing to provide informed consent, attend the lab, and abstain from tobacco/nicotine as required (participants will be instructed to abstain from nicotine/tobacco and/or ENDS use for ≥12h)
• A dual ENDS and tobacco user who reports daily use of ENDS (≥ 3 mg/ml nicotine) or cigarettes (any frequency) AND someday use (≥ 3 days/week) of ENDS (≥ 3 mg/ml nicotine) or cigarettes (any frequency) for the past 3 months or longer

Exclusion criteria

• History of chronic disease or an uncontrolled psychiatric condition
• History of or active cardiovascular disease, low/high blood pressure, seizures, regular use of a prescription medication (except vitamins/birth control)
• Past month use of cocaine, opioids, benzodiazepines, or methamphetamines
• Individuals who report using marijuana >15/30 days
• Women will be excluded if they are breast-feeding or pregnant
• Participants intending to quit tobacco/nicotine use in the next 30 days and referred to cessation treatment

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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130 participants in 8 patient groups, including a placebo group

Combination One - 16μg/s protonated nicotine flux

Experimental group

Description:

The investigators will test the subjective effects of nicotine flux (16μg/s) coupled with one ratio of nicotine form (100% protonated). Following a one-hour observation period, participants will use Subox Mini C in a 10-puff directed (30sec inter-puff interval) bout. One hour after the first bout, participants will be instructed to puff on the device for 60-min ad libitum. Subjective measures (i.e., nicotine dependence, drug effects, product liking, and craving) will be administered 5 times/session: 5 min before and 5 min after onset of the directed bout and 5 min before, halfway into and 5 min after onset of the ad libitum bout.

Treatment:

Combination Product: e-liquid 1

Combination Two - 32μg/s protonated nicotine flux

Experimental group

Description:

The investigators will test the subjective effects of nicotine flux (32μg/s) coupled with one ratio of nicotine form (100% protonated). Following a one-hour observation period, participants will use Subox Mini C in a 10-puff directed (30sec inter-puff interval) bout. One hour after the first bout, participants will be instructed to puff on the device for 60-min ad libitum. Subjective measures (i.e., nicotine dependence, drug effects, product liking, and craving) will be administered 5 times/session: 5 min before and 5 min after onset of the directed bout and 5 min before, halfway into and 5 min after onset of the ad libitum bout.

Treatment:

Combination Product: e-liquid 2

Combination Three - 16μg/s free base nicotine flux

Experimental group

Description:

The investigators will test the subjective effects of nicotine flux (16μg/s) coupled with one ratio of nicotine form (100% free base). Following a one-hour observation period, participants will use Subox Mini C in a 10-puff directed (30sec inter-puff interval) bout. One hour after the first bout, participants will be instructed to puff on the device for 60-min ad libitum. Subjective measures (i.e., nicotine dependence, drug effects, product liking, and craving) will be administered 5 times/session: 5 min before and 5 min after onset of the directed bout and 5 min before, halfway into and 5 min after onset of the ad libitum bout.

Treatment:

Combination Product: e-liquid 3

Combination Four - 32μg/s free base nicotine flux

Experimental group

Description:

The investigators will test the subjective effects of nicotine flux (32μg/s) coupled with one ratio of nicotine form (100% free base). Following a one-hour observation period, participants will use Subox Mini C in a 10-puff directed (30sec inter-puff interval) bout. One hour after the first bout, participants will be instructed to puff on the device for 60-min ad libitum. Subjective measures (i.e., nicotine dependence, drug effects, product liking, and craving) will be administered 5 times/session: 5 min before and 5 min after onset of the directed bout and 5 min before, halfway into and 5 min after onset of the ad libitum bout.

Treatment:

Combination Product: e-liquid 4

Placebo - Combination Five - 0μg/s nicotine flux

Placebo Comparator group

Description:

The investigators will test the subjective effects of nicotine flux (0μg/s) placebo. Following a one-hour observation period, participants will use Subox Mini C in a 10-puff directed (30sec inter-puff interval) bout. One hour after the first bout, participants will be instructed to puff on the device for 60-min ad libitum. Subjective measures (i.e., nicotine dependence, drug effects, product liking, and craving) will be administered 5 times/session: 5 min before and 5 min after onset of the directed bout and 5 min before, halfway into and 5 min after onset of the ad libitum bout.

Treatment:

Combination Product: e-liquid 5

Combination six - 0 ug/s flux; high power/low power

Experimental group

Description:

The investigators will test the subjective effects (perceived mouthful, perceived draw effort, and throat hit) at two power levels (20W and 40 W) with no nicotine in the liquid. Participants will alternate 10 directed puffs (30sec inter-puff interval) between two Subox Mini C devices differing only by the two power levels. Subjective measures will be administered following puff pairs 1\&2, 5\&6, and 9\&10.

Treatment:

Combination Product: e-liquid 6

Combination seven - 32 ug/s flux; high power/low power

Experimental group

Description:

The investigators will test the subjective effects (perceived mouthful, perceived draw effort, and throat hit) at two power levels (20W and 40 W) and a constant nicotine flux of 32 ug/s. Participants will alternate 10 directed puffs (30sec inter-puff interval) between two Subox Mini C devices (20 W; 8mg/ml and 40 W;4 mg/ml). Subjective measures will be administered following puff pairs 1\&2, 5\&6, and 9\&10.

Treatment:

Combination Product: e-liquid 7 and e-liquid 8

Combination seven - 16 ug/s flux; high PG/VG / low PG/VG

Experimental group

Description:

The investigators will test the subjective effects (perceived mouthful, perceived draw effort, and throat hit) at two PG/VG ratios (30/70 and 70/30). Participants will alternate 10 directed puffs (30sec inter-puff interval) between two Subox Mini C devices differing only by the two PG/VG ratios. Subjective measures will be administered following puff pairs 1\&2, 5\&6, and 9\&10.

Treatment:

Combination Product: e-liquid 9 and e-liquid 10