Nicotine Reinforcement and Aversion in Young Adult Light Smokers
Condition: Nicotine Addiction
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Early Phase 1

Summary: 
      The proposed study will examine the threshold for nicotine self-administration (NSA) using
      five different nicotine doses in young adult male and female non-dependent smokers (light and
      intermittent smokers or LITS). We propose a double-blind, placebo-controlled study that will
      enroll 195 individuals, targeting a total of 72 completers (36 male and 36 females). In each
      of the five experimental sessions, smokers will be randomly assigned to one of the five doses
      of nicotine (0.0125, 0.025, 0.05, 0.1 and 0.2 mg/70 kg). The highest dose, 0.2 mg/70 kg,
      corresponds to nicotine delivered by about one or two puffs of a cigarette. At the beginning
      of each experimental session, smokers will sample the assigned both the nicotine dose for
      that experimental session, and the placebo (saline) dose, followed by the opportunity to
      choose between nicotine and placebo for a total of ten choices over a 150-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
    

Detailed description: 
      Aim #1: To assess the threshold reinforcing dose and dose-effect curve for IV NSA at low
      doses in young adult LITS.

      Hypothesis #1A: The threshold reinforcing doses for IV NSA will be between 0.0125 to 0.1
      mg/70 kg.

      Hypothesis #1B: The dose-effect curve for NSA will differ between males and females with
      relatively flat curve in female smokers.

      Aim #2: To assess the threshold and dose-effect curve for the positive and negative/aversive
      subjective effects of IV nicotine at low doses and its relationship to nicotine
      reinforcement.

      Hypothesis #2 A: The threshold for the positive effects will be between 0.0125 to 0.1 mg/70
      kg, for the negative/aversive effect it will be ≥ 0.1 mg/70 kg.

      Hypothesis #2B: Nicotine reinforcement will be positively correlated with the positive and
      negatively correlated with the negative/aversive subjective effects of IV nicotine.

      Exploratory Aims: To examine the influence of nicotine clearance rate on nicotine
      reinforcement threshold and dose-effect curve.
    

Intervention name(s): Saline; Nicotine
Intervention type(s): Drug; Drug
Intervention description(s): 5cc's of saline give at least once.; (0.0125, 0.025, 0.0.5, 0.1 and 0.2 mg/70 kg or about 0.18, 0.36, 0.7, 1.4 and 2.8 µg/kg).
Other intervention name(s): Placebo; IV nicotine
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Nicotine; smokers; vitals associated with smoking