Nicotine Delivery Rate and Its Abuse Potential: Impact of Menthol

Study Overview
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Brief Summary
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A placebo-controlled study to enroll male and female tobacco smokers who will participate in five experimental sessions. subjects will be given an IV infusion of either saline or 1 mg nicotine at rapid, moderate or slow infusion rates (nicotine at 0.24,0.096, 0.048 and 0.024, mcg per kg body weight per sec).

Detailed Description
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A placebo-controlled study that will enroll male and female tobacco smokers' menthol to participate in five experimental sessions. During the experimental session, subjects will be given an IV infusion of either saline or 1 mg nicotine at rapid, moderate or slow infusion rates (nicotine at 0.24,0.096, 0.048 and 0.024, mcg per kg body weight per sec). The infusion conditions for each experimental session will be determined in random order. Aim 1 is to establish a dose-effect curve for positive subjective effects (drug liking and good drug effects) and alleviation of smoking urges, as a function of nicotine delivery rate in menthol and non-menthol cigarette preferring smokers Aim 2 is to establish a dose-effect curve positive subjective effects and alleviation of smoking urges as a function of nicotine delivery rate. Aim 3 is to establish a dose-effect curve for nicotine's effect to alleviate symptoms of nicotine withdrawal in abstinent smokers as a function of nicotine delivery rate. Aim 4 is to establish a dose-effect curve for nicotine's acute cardiovascular health effects. Data from this project will help to establish benchmark values for nicotine's threshold effects that will guide policies on the nicotine yield of tobacco products. Presented is the time frame at which the peak change was strongest by treatment arm. The possible peak numbers could be 1, 3, 5, 7 and 10 minutes.

Official Title
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Nicotine Delivery Rate and Its Abuse Potential: Impact of Menthol

Conditions
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Nicotine Dependence

Intervention / Treatment
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* Drug: Nicotine saline infusion 0.00mcg/kg/s
* Drug: Nicotine infusion 0.24mcg/kg/s
* Drug: Nicotine infusion 0.096mcg/kg/s
* Drug: Nicotine infusion 0.048 mcg/kg/s
* Drug: Nicotine infusion 0.024mcg/kg/s


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Female and male smokers, aged 18 to 35 years, who have been smoking tobacco cigarettes for at least a year Smoke ≥ 5 and less than 20 cigarettes per day; Urine cotinine levels > 100 ng/mL consistent with nicotine intake of an active smoker (23) Not seeking treatment at the time of the study for nicotine dependence; 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 or psychiatric disorders that the physician investigator deems as contraindicated for the subject to be in the study Regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics) Current alcohol or substance dependence for any other recreational or prescription drugs other than nicotine Use of e-cigarettes more than 10 days in the past 30 days Urine drug screening indicating recent illicit drugs use (with the exception of marijuana).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Single blind, placebo-controlled, mixed-design with nicotine delivery as a within-subjects factor.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nicotine saline infusion 0.00mcg/kg/s<br>0.00 mcg/kg/s The day order will be randomized per day | Drug: Nicotine saline infusion 0.00mcg/kg/s<br>* saline 0.00mcg/kg/s<br>* Other names: nicotine infusion;|
| Experimental: nicotine infusion 0.24mcg/kg/s<br>0.24mcg/kg/s The day order will be randomized per day | Drug: Nicotine infusion 0.24mcg/kg/s<br>* nicotine 0.24mcg/kg/s<br>* Other names: nicotine infusion;|
| Experimental: nicotine infusion 0.096mcg/kg/s<br>0.096mcg/kg/s The day order will be randomized per day | Drug: Nicotine infusion 0.096mcg/kg/s<br>* nicotine 0.096mcg/kg/s<br>* Other names: nicotine infusion;|
| Experimental: nicotine infusion 0.048mcg/kg/s<br>0.048mcg/kg/s The day order will be randomized per day | Drug: Nicotine infusion 0.048 mcg/kg/s<br>* nicotine 0.048mcg/kg/s<br>* Other names: nicotine infusion;|
| Experimental: nicotine infusion 0.024mcg/kg/s<br>0.048mcg/kg/s The day order will be randomized per day | Drug: Nicotine infusion 0.024mcg/kg/s<br>* nicotine 0.024mcg/kg/s<br>* Other names: nicotine infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Stimulatory Effects | The peak change in the intensity of subjective effects as measured by the DEQ: Drug stimulatory effects questionnaire; Eleven questions with a minimum score of 0 to a maximum score of 100. Presented is the DEQ score at which the peak change was strongest by treatment arm. Each session took approximately 60 minutes, however the measures were only collected up to 10 minutes post infusion. This correction to the outcome time frame was made when the results were entered. Data were collected at 1, 3, 5, 7 and 10 minute intervals. The outcome measure title DEQ Stimulatory Effects measure was also updated. | up to 10 minutes | 
| Peak Changes on Items of the Drug Effects Questionnaire (DEQ) - Pleasurable Effects | The peak change in the intensity of subjective effects as measured by the DEQ: Drug pleasurable effects questionnaire; Eleven questions with a minimum score of 0 to a maximum score of 100. Presented is the DEQ score at which the peak change was strongest by treatment arm. Each session took approximately 60 minutes, however the measures were only collected up to 10 minutes post infusion. This correction to the outcome time frame was made when the results were entered. Data were collected at 1, 3, 5, 7 and 10 minute intervals. The outcome measure title DEQ Stimulatory Effects measure was also updated. | up to 10 minutes post infusion |