Nicotine, Non-Smokers With and Without ADHD, and Genetics Study
Condition: Non-smoker; ADHD
MeSH terms: Attention Deficit Disorder with Hyperactivity
Study type: Interventional
Phase: Phase 1

Summary: 
      The overall goal of the proposed research is to evaluate the behavioral and genetic
      mechanisms of smoking risk in non-smoking young adults (aged 18-25 years of age) with and
      without ADHD using a novel laboratory-based model of intranasal nicotine administration.

      Study Hypotheses:

        1. that nicotine will produce greater positive and fewer negative/aversive subjective
           effects in individuals with ADHD. The study team also hypothesizes that nicotine will
           improve performance to a greater degree in those with ADHD.

        2. that individuals in the ADHD group will exhibit an increase in choices for nicotine vs.
           placebo in both conditions (i.e., main effect) and that this effect will be more
           pronounced in the High Demand vs. Low Demand conditions (i.e. Group x Condition
           interaction). Also that greater performance enhancing effects of nicotine will be
           associated with greater nicotine choice during the high demand cognitive condition.

        3. that the main effects of ADHD status on nicotine reinforcement will be heightened in the
           presence of certain genotypes. Also that the main effects of ADHD status on nicotine
           reinforcement will be heightened in the presence of certain genotypes. Finally that
           exposure to nicotine will alter epigenetic patterns in DNA
    

Detailed description: 
      Individuals with Attention Deficit Hyperactivity Disorder (ADHD) are more likely to smoke
      cigarettes than the general population, start smoking at a younger age, progress to regular
      use and dependence more quickly, and have a harder time quitting. The specific factors that
      confer risk for smoking-related outcomes among those with ADHD have not been thoroughly
      evaluated, though a range of possibilities exist. The overall goal of the proposed research
      is to evaluate the behavioral and genetic mechanisms of smoking risk in non-smoking young
      adults (aged 18-25 years of age) with and without ADHD using a novel laboratory-based model
      of intranasal nicotine administration. Target completion population of the study is 150 (75
      ADHD, 75 CTRL), although the population potentially screened will be 200. The investigators
      will systematically assess the effects of two doses of intranasally administered nicotine
      versus placebo. In addition, nicotine self-administration will be evaluated under conditions
      that are likely to be more cognitively challenging among individuals with ADHD. If the
      subject passes screen and their status as never smoking up to 1 cigarette in their lifetime,
      they will be scheduled for a the first of five experimental sessions: 3 fixed dose sessions,
      followed by 2 choice sessions. Each of the 3 fixed dose sessions will be identical except for
      the dose of nicotine evaluated. During choice sessions, the nicotine reinforcement procedures
      will be implemented. Finally to assess the moderating effects of genotype on the reinforcing
      effects of nicotine in non-smokers analyses will focus primarily with hierarchical regression
      models that covary gender and population substructure to assess effects of genotype on
      nicotine sensitivity outcomes. Further epigenetics analysis will be conducted, related to the
      initial nicotine exposure at the Fixed Dose Sessions.
    

Intervention name(s): Nicotine nasal spray; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): This study will use nicotine nasal spray to safely and effectively model the effects of initial smoking experiences in nonsmokers. Neither the safety nor the effectiveness of this drug will be assessed. The overall goal of the proposed research is to evaluate the behavioral and genetic mechanisms of smoking risk in non-smoking young adults (aged 18-25 years of age) with and without ADHD using a novel laboratory-based model of intranasal nicotine administration. The effects of two doses of intranasally administered nicotine versus placebo will be assessed. In addition, nicotine self-administration will be evaluated under conditions that are likely to be more cognitively challenging among individuals with ADHD.
Other intervention name(s): Sterile normal saline.
Intervention MeSH terms: Nicotine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Nonsmoker; ADHD; Nicotine; Nicotine Nasal Spray; Nicotine Reinforcement