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 male and female smokers with or without nicotine dependence (light and intermittent smokers). The investigators propose a double-blind, placebo-controlled study that will enroll 150 individuals with 32 male and 32 female smokers with a total of 64 completers, (16 of each group will be dependent and 16 will be non-dependent). Smokers will participate in four sessions: four test sessions. In each of the four test 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 test session, smokers will sample the assigned nicotine dose and placebo (saline) and then have the opportunity to choose between nicotine and placebo for a total of five choices over a 90-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).
Aim #1: To further characterize the reinforcing threshold and dose-response curve for IV nicotine self-administration in male and female smokers with or without nicotine dependence. The reinforcing effects of nicotine will be determined by the number of IV nicotine self-administrations.
Hypothesis 1a) female smokers, compared to males, will have a lower threshold and a steeper slope for nicotine reinforcement, indicating greater sensitivity to nicotine.
Hypothesis 1b) non-dependent smokers, compared to dependent smokers, will have a lower threshold and a steeper slope for nicotine reinforcement.
Aim#2: To further characterize the threshold and dose-response curve for the subjective-rewarding effects of self-administered IV nicotine in male and female smokers with or without nicotine dependence. The subjective-rewarding effects of nicotine will be determined by the "good effects" and "drug liking" items of the Drug Effects Questionnaire.
Hypothesis 2a) female smokers, compared to males, will have a lower threshold and a steeper slope for the subjective-rewarding effects of nicotine.
Hypothesis 2b) non-dependent smokers, compared to dependent smokers, will have a lower threshold and a steeper slope for the subjective-rewarding effects of nicotine, indicating greater sensitivity to nicotine.
- 18 Years - 50 Years
- Female and male smokers, aged 18 to 50 years, who have been smoking for at least a
- for non-dependent smokers, urine cotinine levels < 200 ng/mL and not-fulfill DSM-IV
criteria for nicotine dependence;
- for dependent smokers, urine cotinine levels = 200 ng/mL and fulfill DSM-IV criteria
for nicotine dependence;
- not seeking treatment at the time of the study for nicotine dependence;
- in good health as verified by medical history, screening examination, and screening
- for women, not pregnant as determined by pregnancy screening, nor breast feeding, and
using acceptable birth control methods.
- history of major medical illnesses that the physician investigator deems as
contraindicated for the subject to be in the study;
- regular use of psychotropic medication (antidepressants, antipsychotics, or
anxiolytics) and recent psychiatric diagnosis and treatment for Axis I disorders
including major depression, bipolar affective disorder, schizophrenia or panic
- abuse of alcohol or any other recreational or prescription drugs.
- Yale University
- October 2011
- Last Updated:
- December 15, 2011
- Study HIC#:
Clinicaltrials.gov ID: NCT01495819