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

Nicotine Flux, a Potentially Powerful Tool for Regulating Nicotine Delivery From Electronic Cigarettes: Significance of Nicotine Flux to the Rate of Nicotine Delivery and Subjective Effect

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.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence; Nicotine Vaping; Nicotine Addiction
• Intervention / Treatment: Combination product: e-liquid 2; Combination product: e-liquid 3; Combination product: e-liquid 4; Combination product: e-liquid 5; Combination product: e-liquid 6; Combination product: e-liquid 7 and e-liquid 8; Combination product: e-liquid 9 and e-liquid 10; Combination product: e-liquid 1

Detailed 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 (15 and 35μg/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. 10 of the participants that completed AIM 2 will be asked to attend our lab at AUB for one additional visit, where they will be assigned either a high flow or low flow ENDS. During the visit, participants will undertake three smoking bouts consisting of 10 puffs each, where they will be presented with alternating puffs of the assigned device in which a specific ENDS design variable is systematically varied between puffs. Puff topography, inhalation behavior, and subjective effects related to sensory feedback will be recorded. We hypothesize that power and liquid composition variations will result in immediate and reversible changes in puffing/inhalation behavior.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Lebanon
  • Beirut
    • Beirut, Beirut, Lebanon, 11-0236
      • American University of Beirut

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo - Combination Five - 0μg/s nicotine flux; 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.	Combination product: e-liquid 5; 30/70 PG/VG ratio with nicotine concentration 0mg/ml (placebo)
Experimental: Combination One - 15μg/s protonated nicotine flux; The investigators will test the subjective effects of nicotine flux (15μg/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.	Combination product: e-liquid 1; 30/70 propylene glycol/vegetable glycerin ratio with nicotine concentration 4mg/ml protonated
Experimental: Combination Two - 35μg/s protonated nicotine flux; The investigators will test the subjective effects of nicotine flux (35μg/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.	Combination product: e-liquid 2; 30/70 PG/VG ratio with nicotine concentration 10mg/ml protonated
Experimental: Combination Three - 15μg/s free base nicotine flux; The investigators will test the subjective effects of nicotine flux (15μg/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.	Combination product: e-liquid 3; 30/70 PG/VG ratio with nicotine concentration 4mg/ml free base
Experimental: Combination Four - 35μg/s free base nicotine flux; The investigators will test the subjective effects of nicotine flux (35μg/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.	Combination product: e-liquid 4; 30/70 PG/VG ratio with nicotine concentration 10mg/ml freebase
Experimental: Combination six - 0μg/s flux; high power/low power; 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.	Combination product: e-liquid 6; 30/70 PG/VG ratio with nicotine concentration 0mg/ml
Experimental: Combination seven - 35μg/s flux; high power/low power; 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 35 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.	Combination product: e-liquid 7 and e-liquid 8; e-liquid 7: 30/70 PG/VG ratio with nicotine concentration 4mg/ml protonated e-liquid 8: 30/70 PG/VG ratio with nicotine concentration 8mg/ml protonated
Experimental: Combination eight - 15μg/s flux; high PG(propylene glycol)/VG(vegetable glycerin) / low PG/VG; The investigators will test the subjective effects (perceived mouthful, perceived draw effort, and throat hit) at two propylene glycol/vegetable glycerin 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.	Combination product: e-liquid 9 and e-liquid 10; e-liquid 9: 30/70 PG/VG ratio with nicotine concentration 4mg/ml protonated e-liquid 10: 70/30 PG/VG ratio with nicotine concentration 4mg/ml protonated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective Effects - Strong Flavor (Combinations 1-5)	Strong flavor will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled magnitude scale (gLMS) on a subjective scale (0-10, No sensation - Strongest Imaginable), with higher scores indicating a stronger perceived flavor.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Harshness/Irritancy (Combinations 1-5)	Harshness/irritancy will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled magnitude scale (gLMS) on a subjective scale (0-10, No sensation - Strongest Imaginable), with higher scores indicating harsher/more irritating effects.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Throat Hit (Combinations 1-5)	Throat hit will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled magnitude scale (gLMS) on a subjective scale (0-10, No sensation - Strongest Imaginable), with higher scores indicating a stronger throat hit.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Overall Like: Flavor (Combinations 1-5)	Overall like: flavor will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled hedonic scale (LHS) on a subjective scale (0-10, most disliked - most liked), with higher scores indicating the flavor was liked more.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Overall Like: Harshness (Combinations 1-5)	Overall like: harshness will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled hedonic scale (LHS) on a subjective scale (0-10, most disliked - most liked), with higher scores indicating the harshness was liked more.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Overall Like: Throat Hit (Combinations 1-5)	Overall like: throat hit will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled hedonic scale (LHS) on a subjective scale (0-10, most disliked - most liked), with higher scores indicating the throat hit was liked more.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Overall Like: Warmth (Combinations 1-5)	Overall like: warmth will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled hedonic scale (LHS) on a subjective scale (0-10, most disliked - most liked), with higher scores indicating the warmth was liked more.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Satisfying (Combinations 1-5)	Satisfying will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating greater satisfaction.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Pleasant (Combinations 1-5)	Pleasant will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating greater pleasantness.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Taste Good (Combinations 1-5)	Taste good will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating better taste.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Calm (Combinations 1-5)	Calm will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating feeling calmer.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Concentrate (Combinations 1-5)	Concentrate will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating better ability to concentrate.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Awake (Combinations 1-5)	Awake will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating feeling more awake/alert.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Reduce Hunger (Combinations 1-5)	Reduce hunger will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating greater reduction in hunger.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Dizzy (Combinations 1-5)	Dizzy will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating greater dizziness.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Feeling Sick (Combinations 1-5)	Feeling sick will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating feeling more sick.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Want it Right Now (Combinations 1-5)	Want it right now will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating a stronger immediate desire for the product.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Smell (Combinations 1-5)	Smell will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating a stronger perceived smell. This item is drawn from the Electronic Cigarette Specific Effects Questionnaire, a modified/expanded version of the modified Cigarette Evaluation Questionnaire (mCEQ; Cappelleri et al., 2007) developed for ENDS. Participants rate the item on a 0-10 scale immediately following each bout. Item wording: 'Did the e-cig produce a smell?' (0 = not at all, 10 = extremely).	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Visible Vapor (Combinations 1-5)	Visible vapor will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating more visible vapor.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Importance Vapor (Combinations 1-5)	Importance vapor will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating vapor visibility mattered more to the participant. This item is drawn from the Electronic Cigarette Specific Effects Questionnaire, a modified/expanded version of the modified Cigarette Evaluation Questionnaire (mCEQ; Cappelleri et al., 2007) developed for ENDS. Participants rate the item on a 0-10 scale immediately following each bout. Item wording: 'Is the vapor/cloud of the e-cig important to you?' (0 = not at all, 10 = extremely).	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Subjective Effects - Puffs Similar (Combinations 1-5)	Puffs similar will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating the puffs were perceived as more similar to the participant's usual product.	Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.
Smoking Urges - Brief Factor 1 (Intention/Desire)	Brief Factor 1 (Intention/Desire) will be assessed by the Questionnaire of Smoking Urges-Brief (QSU-Brief; Tiffany & Drobes, 1991; Toll et al., 2006). Factor 1 is the sum of 6 items, each rated on a 0-10 scale (0=strongly disagree, 10=strongly agree), yielding a total score range of 0-60, with higher scores indicating stronger urges.	Assessed before and after the directed bout (Bout 1), and before, midway through, and after the ad libitum bout (Bout 2).
Smoking Urges - Brief Factor 2 (Relief of Neg. Affect)	Brief Factor 2 (Relief of Neg. Affect) will be assessed by the Questionnaire of Smoking Urges-Brief (QSU-Brief; Tiffany & Drobes, 1991; Toll et al., 2006). Factor 2 is the sum of 4 items, each rated on a 0-10 scale (0=strongly disagree, 10=strongly agree), yielding a total score range of 0-40, with higher scores indicating stronger urges.	Assessed before and after the directed bout (Bout 1), and before, midway through, and after the ad libitum bout (Bout 2).
Withdrawal Symptoms - Minnesota Nicotine Withdrawal Scale (MNWS; Based on Hughes and Hatsukami, 1986)	The Minnesota Nicotine Withdrawal Scale (MNWS; based on Hughes and Hatsukami, 1986 questionnaire) was measured using composite mean of MNWS items (irritability, anxiety, difficulty concentrating, restlessness, hunger/appetite, Impatient, depression, desire for sweets and craving) on a 0-10 scale (Not at all - Extremely), with higher scores indicating greater withdrawal severity.	Assessed before and after the directed bout (Bout 1), and before, midway through, and after the ad libitum bout (Bout 2).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Puff Duration	Puff duration combination 1,2,3,4 & 5	Will be measured during the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout
Number of Puffs	Measured topography Total Number of Puffs (puffs).	Will be measured during the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout
Puffing Time	Measured topography Average Puffing time (sec).	Will be measured during the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout
Inter Puff Interval	Measured topography Average Inter Puff Interval (sec).	Will be measured during the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout
Flow Rate	Measured topography Average Flow rate (Liters per minute: LPM).	Will be measured during the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout
Mouth-level PM	Mouth-level PM (Particulate matter) dose estimated using the REALTIME real-time in-situ sampling device, which collects 5% of the aerosol at the mouthpiece during each puff; values are reported as the total session dose (5% fraction × 20), in mg.	Will be measured after the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout
Mouth-level Nicotine	Mouth-level nicotine dose estimated using the REALTIME real-time in-situ sampling device, which collects 5% of the aerosol at the mouthpiece during each puff; values are reported as the total session dose (5% fraction × 20), in mg.	Will be measured after the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout
Puff Duration - Combination 6,7 & 8	Measured topography Average Puff Duration (sec) - using Subox mini C. Puffs were administered in alternating order using block randomization; for Combination Six, odd puffs were delivered at 20W and even puffs at 40W; for Combination Seven, odd puffs were delivered at 20W/8mg/mL and even puffs at 40W/4mg/mL; for Combination Eight, odd puffs were delivered at 30/70 PG/VG and even puffs at 70/30 PG/VG.	Will be measured during the approximately 5-minute, 10-puff use bout
Sensory Feedback - Perceived Mouthful - Using Kangertech Subox Mini C (Sub-ohm Device)	The perceived mouthful will be assessed using the following question: "How would you rate the amount of smoke filling your mouth during the puff you just smoked?". A subjective visual analog scale will be used (1-5, barely any smoke- a lot of smoke) with higher scores indicating higher mouthful. Puffs were administered in alternating order using block randomization; for Combination Six, odd puffs were delivered at 20W and even puffs at 40W; for Combination Seven, odd puffs were delivered at 20W/8mg/mL and even puffs at 40W/4mg/mL; for Combination Eight, odd puffs were delivered at 30/70 PG/VG and even puffs at 70/30 PG/VG.	Will be measured during the approximately 5-minute, 10-puff use bout
Sensory Feedback - Perceived Draw Effort - Using Kangertech Subox Mini C (Sub-ohm Device)	The perceived draw effort will be assessed using the following question: " How would you rate the effort needed to draw the puff you just smoked?". A subjective visual analog scale will be used (1-5, easy- hard) with higher scores indicating harder draw effort. Puffs were administered in alternating order using block randomization; for Combination Six, odd puffs were delivered at 20W and even puffs at 40W; for Combination Seven, odd puffs were delivered at 20W/8mg/mL and even puffs at 40W/4mg/mL; for Combination Eight, odd puffs were delivered at 30/70 PG/VG and even puffs at 70/30 PG/VG.	Will be measured during the approximately 5-minute, 10-puff use bout
Sensory Feedback - Throat Hit - Using Kangertech Subox Mini C (Sub-ohm Device)	The perceived Throat hit will be assessed using the following question: "How would you describe the throat hit of the device you just used" (0-100 General Labeled Magnitude Scale; anchors: "barely detectable" to "strongest imaginable"). Puffs were administered in alternating order using block randomization; for Combination Six, odd puffs were delivered at 20W and even puffs at 40W; for Combination Seven, odd puffs were delivered at 20W/8mg/mL and even puffs at 40W/4mg/mL; for Combination Eight, odd puffs were delivered at 30/70 PG/VG and even puffs at 70/30 PG/VG.	Will be measured during the approximately 5-minute, 10-puff use bout

Collaborators and Investigators

• Sponsor: American University of Beirut Medical Center
• Collaborators: National Institute on Drug Abuse (NIDA); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Soha Talih, PhD, American University of Beirut Medical Center

Publications and helpful links

General Publications

• El-Hellani A, Hanna E, Sharma M, Blohowiak R, Joseph P, Eid T, Nadim H, El-Hage R, Salman R, Karaoghlanian N, Adeniji A, Salam S, Talih F, Elbejjani M, Breland A, Eissenberg T, Shihadeh A, Baldassarri SR, Talih S. Nicotine flux as a powerful tool for regulating nicotine delivery from e-cigarettes: Protocol of two complimentary randomized crossover clinical trials. PLoS One. 2023 Sep 21;18(9):e0291786. doi: 10.1371/journal.pone.0291786. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2022
• Primary Completion (Actual): July 11, 2025
• Study Completion (Actual): July 11, 2025

Study Registration Dates

• First Submitted: June 8, 2022
• First Submitted That Met QC Criteria: June 20, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Actual): September 18, 2026
• Last Update Submitted That Met QC Criteria: August 24, 2026
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Nicotine; ENDS; Vaping; Aerosol; Nicotine Flux; Combustible
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Behavior; Smoking; Tobacco Use Disorder; Vaping
• Other Study ID Numbers: American University Of Beirut; 1R01DA052565-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Participants data will not be available to other researchers

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