Effects of Flavors on Nicotine Reinforcement in Smokers

Study Overview
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Brief Summary
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To examine the acute reinforcing effects of menthol, a fruit flavor (green apple) or a fruit flavor plus menthol, alone or in combination with nicotine in smokers. Flavors will be administered by inhalation via electronic cigarettes (e-cigarettes) and nicotine will be administered intravenously. The reinforcing drug effects will be measured with the drug effects questionnaire (DEQ).

Detailed Description
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This is a proposed double-blind, crossover study that enrolls young adult smokers who prefer menthol cigarettes. The study will consist of an adaptation session and three test sessions. In the adaptation session, participants will practice using the e-cigarette by sampling the flavors to be used in the test sessions. The test sessions will be performed following overnight abstinence from tobacco. Across the three test sessions, participants will be assigned to a random sequence of the three different e-cigarette conditions: menthol, green apple or menthol plus green apple, a different flavor condition for each test session. In each test session, just after the assigned flavor is delivered via the e-cigarette, participants will receive a random order of one intravenous delivery of saline, and two intravenous deliveries of nicotine (3.6 mcg/kg and 7 mcg/kg or 0.25 mg/70 kg and 0.5 mg/70kg), one hour apart. The test sessions will be performed at least 24 hours apart to minimize carryover nicotine effects. The main outcome measure will be subjective drug effects as measured with the Drug Effects Questionnaire (DEQ). Other outcomes include cardiovascular measures, cognitive performance, and self-report measures of nicotine withdrawal and craving. Cardiovascular measures include heart rate, systolic and diastolic blood pressure. Cognitive performance will be assessed with the Stroop test, mathematical processing test (MPT), and continuous performance test (CPT). Nicotine withdrawal measures will be measured with the Minnesota Nicotine Withdrawal Symptom Checklist (M-NWSC) and the Brief Questionnaire on Smoking Urges (BQSU).

Official Title
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Effects of Flavors on Nicotine Reinforcement in Smokers

Conditions
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Nicotine Dependence

Intervention / Treatment
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* Drug: IV nicotine
* Drug: Menthol flavor
* Drug: green apple
* Drug: green apple and menthol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and male mentholated cigarette smokers, aged 18 to 30 years; history of smoking for the past 12 months, at least one cigarette per day; smoking status is verified with urinary cotinine levels above 10 ng/ml; not seeking treatment for nicotine dependence at the time of study entry in good health as verified by medical history, screening examination, and screening laboratory tests; for women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods. Exclusion Criteria: History of major medical illnesses that the physician investigator deems as contraindicated for the patient to be in the study; regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics); psychiatric diagnosis and / or treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia or panic disorder in the past month; abuse of alcohol or any other recreational or prescription drugs in the past 30 days; any allergy to propylene glycol or menthol; and 6) aversion to green apple flavor.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Mixed-effects models will be used to test the study hypotheses. These models allow for different numbers of observations per subject, use all available data on each subject, and are unaffected by randomly missing data.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Menthol e-liquid<br>Menthol Flavor + IV saline Menthol Flavor + IV nicotine (0.25mg/70kg) Menthol Flavor + IV nicotine (0.5mg/70kg) | Drug: IV nicotine<br>* Subjects in each arm will receive three infusions in a random order one hour apart. The infusions will be saline, 0.25mg/70kg and 0.5mg/70kg<br>* Other names: nicotine, e-liquid;Drug: Menthol flavor<br>* American e-liquids' menthol flavor used in e-cigarettes will be used as the placebo comparator<br>* Other names: menthol American e-liquids;Drug: green apple<br>* green apple will be added to the menthol flavor<br>* Other names: green apple American e-liquids;Drug: green apple and menthol<br>* menthol and green apple will be the active intervention<br>* Other names: green apple and menthol flavor American e-liquids;|
| Active Comparator: green apple e-liquid<br>Green apple + IV saline Green apple + IV nicotine (0.25mg/70kg) Green apple + IV nicotine (0.5mg/70kg) | Drug: IV nicotine<br>* Subjects in each arm will receive three infusions in a random order one hour apart. The infusions will be saline, 0.25mg/70kg and 0.5mg/70kg<br>* Other names: nicotine, e-liquid;Drug: Menthol flavor<br>* American e-liquids' menthol flavor used in e-cigarettes will be used as the placebo comparator<br>* Other names: menthol American e-liquids;Drug: green apple<br>* green apple will be added to the menthol flavor<br>* Other names: green apple American e-liquids;Drug: green apple and menthol<br>* menthol and green apple will be the active intervention<br>* Other names: green apple and menthol flavor American e-liquids;|
| Active Comparator: green apple and menthol e-liquid<br>Green apple and menthol + IV saline Green apple and menthol + IV nicotine (0.25mg/70kg) Green apple and menthol + IV nicotine (0.5mg/70kg) | Drug: IV nicotine<br>* Subjects in each arm will receive three infusions in a random order one hour apart. The infusions will be saline, 0.25mg/70kg and 0.5mg/70kg<br>* Other names: nicotine, e-liquid;Drug: Menthol flavor<br>* American e-liquids' menthol flavor used in e-cigarettes will be used as the placebo comparator<br>* Other names: menthol American e-liquids;Drug: green apple<br>* green apple will be added to the menthol flavor<br>* Other names: green apple American e-liquids;Drug: green apple and menthol<br>* menthol and green apple will be the active intervention<br>* Other names: green apple and menthol flavor American e-liquids;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ). | The (DEQ) Drug Effects Questionnaire has eleven questions with a minimum score of 0 to a maximum score of 100. Peak values from each time points were calculated for the change in the intensity of positive subjective effects as measured with these peak values for like and want more were averaged to obtain a summary score to represent the feel good drug effects composite factor. Higher scores for each DEQ represent greater endorsement of that subjective effect (e.g., on the like drug scale a response of 90 represents greater liking than a response of 50). | up to 3 hours per test session. |