Smoking by IV Pulsed Nicotine

Study Overview
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Brief Summary
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To establish a dose-effect curve for nicotine's abuse potential as a function of nicotine dose and delivery rate. Pulsed IV nicotine administration will be used as it closely matches nicotine delivery by inhaled tobacco use.

Detailed Description
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Both sub-studies will enroll male and female tobacco cigarette smokers. This study will examine the feasibility of the proposed study parameters in a total of 10 completers. In a crossover design, participants will be tested under 5 conditions: 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries). The main outcome measures will be self-report drug effects and urges to smoke cigarettes. The investigators hypothesize that the abuse potential and alleviation of smoking urges are produced by nicotine as a function of nicotine dose and delivery rate. This study is complete with 13 enrolled and 10 completers

Official Title
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Modeling Tobacco Smoking by IV Pulsed Nicotine in Smokers

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: Nicotine 0.2mcg/kg/s and 1.0mcg/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 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; and 6) 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: placebo-controlled, mixed-design with nicotine dose as a between-subject and nicotine delivery rate as a within-subject factor.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nicotine infusion 0.2mg<br>nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) The day order will be randomized over 5 days. | Drug: Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s<br>* Nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).<br>* Other names: nicotine infusion;|
| Experimental: nicotine infusion 2.0mg<br>0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), | Drug: Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s<br>* Nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).<br>* Other names: nicotine infusion;|
| Experimental: nicotine infusion 1.0mg<br>1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) | Drug: Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s<br>* Nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).<br>* Other names: nicotine infusion;|
| Experimental: nicotine infuison 1.0mg<br>1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries). | Drug: Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s<br>* Nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).<br>* Other names: nicotine infusion;|
| Placebo Comparator: Saline<br>saline delivered over 2minutes ,2.5minutes,10 minutes | Drug: Nicotine 0.2mcg/kg/s and 1.0mcg/kg/s<br>* Nicotine infusion 0.2 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries), 0.2mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries), 1.0 mg nicotine delivered over 2.5 minutes (5 pulsed-nicotine deliveries) and 1.0 mg nicotine delivered over 10 min (20 pulsed-nicotine deliveries).<br>* Other names: nicotine infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate will be used to see the dose effect | the dose-effect curves of nicotine dose and delivery rate in heart rate | During nicotine infusion max of ten minutes |