Intravenous (IV) Nicotine Self Administration: Dose Ranging and Sex Differences in Smokers
Trial Purpose and Description
The proposed study will examine the threshold for nicotine self-administration using four different nicotine doses in young adult male and female smokers without nicotine dependence (light and intermittent smokers or LITS). We propose a double-blind, placebo-controlled study that will enroll 195 individuals with 36 male and 36 female smokers and a total of 72 completers. Smokers will participate in five Lab sessions: one adaptation and four experimental sessions. In each of the four experimental sessions, smokers will be randomly assigned to one of the four doses of nicotine (1.5, 3.0, 4.5, and 6.0 mcg/kg, or about 0.1, 0.2, 0.3, and 0.4 mg/70 kg). At the beginning of each experimental session, smokers will sample the assigned nicotine dose for that experimental session, and placebo (saline), and then have the opportunity to choose between nicotine and placebo for a total of ten choices over a 180-minute period. The main outcomes will be threshold dose (the minimum dose of nicotine that is self-administered more than placebo) and the slope of dose-response for nicotine self-administration (changes in nicotine self-administration per unit change in nicotine dose). We will also collect measures of nicotine intake (cotinine), nicotine clearance (3-hydroxycotinine (3-HC) / cotinine), and self-report drug effects. Changes in smoking behavior and the use of other tobacco products will be assessed during follow-up visits at 3, 6 and 12 months. Urine cotinine and self-report measures of tobacco use will be collected.
Aim #1: To characterize the reinforcing threshold and dose-response function for nicotine reinforcement in young adult LITS. Hypothesis #1A: The reinforcing threshold for IV nicotine will range from 1.5 to 6.0 µg/kg. Hypothesis #1B: The dose-response curve for NSA will be increasing steeply above the reinforcement threshold and will be relatively flat in higher doses of nicotine.
Aim #2: To characterize the threshold and dose-response function for the subjective-rewarding effects of nicotine in young adult LITS. This outcome will be determined by the "good effects" and "drug liking" items of the Drug Effects Questionnaire. Hypothesis #2: The threshold for the subjective-reinforcing effects of IV nicotine will range from 1.5 to 6.0 µg/kg.
Aim #1: To examine gender differences for Specific Aims #1 and #2. Aim #2: To explore if higher reinforcement threshold predicts increases in nicotine intake at 3, 6 and 12-month follow-up.
Aim #3: To examine the association between baseline 3-HC / cotinine ratio and nicotine reinforcement threshold.
Aim #4: To compare daily light to intermittent smokers for threshold and dose response-function for nicotine reinforcement.
- 18 Years - 25 Years
Inclusion criteria: 1) Female and male smokers, aged 18 to 25 years, who have been smoking
for at least a year, and a life-time consumption of at least 100 cigarettes; 2) smoke
more frequently than once a week and =5 cpd; 3) FTND score <3 indicating no or minimal
evidence for nicotine dependence and not meeting DSM-IV criteria for nicotine
dependence;3) ; 4) not seeking treatment at the time of the study for nicotine dependence;
5) in good health as verified by medical history, screening examination, and screening
laboratory tests; 6) for women, not pregnant as determined by pregnancy screening, nor
breast feeding, and using acceptable birth control methods.
Exclusion criteria: 1) history of major medical illnesses that the physician investigator
deems as contraindicated for the subject to be in the study; 2) requirement of any form of
regular psychotropic medication (antidepressants, antipsychotics, or anxiolytics) or
psychiatric diagnosis and treatment for psychiatric disorders including major depression,
bipolar disorder, schizophrenia in the past 6 months; and 3) current dependence to alcohol
or any other recreational or prescription drugs and; 4) daily use of smokeless tobacco
products or exclusive daily use of e-cigarettes (non-daily users will be included).
- Yale University
- October 2011
- Last Updated:
- March 17, 2014
- Study HIC#:
Clinicaltrials.gov ID: NCT01495819