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Effects of Flavors on Nicotine Reinforcement in Smokers

Early Phase 1
Completed
Conditions
Nicotine Dependence
Interventions
Registration Number
NCT03243630
Lead Sponsor
Yale University
Brief Summary

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

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
26
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.

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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.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Menthol e-liquidIV nicotineMenthol Flavor + IV saline Menthol Flavor + IV nicotine (0.25mg/70kg) Menthol Flavor + IV nicotine (0.5mg/70kg)
green apple e-liquidIV nicotineGreen apple + IV saline Green apple + IV nicotine (0.25mg/70kg) Green apple + IV nicotine (0.5mg/70kg)
green apple and menthol e-liquidgreen apple and mentholGreen apple and menthol + IV saline Green apple and menthol + IV nicotine (0.25mg/70kg) Green apple and menthol + IV nicotine (0.5mg/70kg)
green apple e-liquidMenthol flavorGreen apple + IV saline Green apple + IV nicotine (0.25mg/70kg) Green apple + IV nicotine (0.5mg/70kg)
Menthol e-liquidgreen appleMenthol Flavor + IV saline Menthol Flavor + IV nicotine (0.25mg/70kg) Menthol Flavor + IV nicotine (0.5mg/70kg)
green apple e-liquidgreen apple and mentholGreen apple + IV saline Green apple + IV nicotine (0.25mg/70kg) Green apple + IV nicotine (0.5mg/70kg)
green apple and menthol e-liquidMenthol flavorGreen apple and menthol + IV saline Green apple and menthol + IV nicotine (0.25mg/70kg) Green apple and menthol + IV nicotine (0.5mg/70kg)
Menthol e-liquidgreen apple and mentholMenthol Flavor + IV saline Menthol Flavor + IV nicotine (0.25mg/70kg) Menthol Flavor + IV nicotine (0.5mg/70kg)
green apple and menthol e-liquidIV nicotineGreen apple and menthol + IV saline Green apple and menthol + IV nicotine (0.25mg/70kg) Green apple and menthol + IV nicotine (0.5mg/70kg)
Menthol e-liquidMenthol flavorMenthol Flavor + IV saline Menthol Flavor + IV nicotine (0.25mg/70kg) Menthol Flavor + IV nicotine (0.5mg/70kg)
green apple e-liquidgreen appleGreen apple + IV saline Green apple + IV nicotine (0.25mg/70kg) Green apple + IV nicotine (0.5mg/70kg)
green apple and menthol e-liquidgreen appleGreen apple and menthol + IV saline Green apple and menthol + IV nicotine (0.25mg/70kg) Green apple and menthol + IV nicotine (0.5mg/70kg)
Primary Outcome Measures
NameTimeMethod
The Reinforcing Drug Effects Will be Measured With the Drug Effects Questionnaire (DEQ).up to 3 hours per test session.

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).

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Veterans Affairs

🇺🇸

West Haven, Connecticut, United States

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