Nicotine, Non-Smokers With and Without ADHD, and Genetics Study

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.

Inclusion Criteria:

1. 18-25 years of age.

2. male or female; if female of childbearing potential, must be using an acceptable form
of contraception.

3. ADHD Diagnosis:

1. for ADHD Groups: confirmed diagnosis, any subtype as determined by the clinician
administered CAADID and clinical interview.

2. for Control Groups: NO diagnosis of ADHD as determined by clinician administered
CAADID and clinical interview.

4. ADHD Symptom Ratings:

1. for ADHD Groups: T-Score > 65 on one of the DSM-IV relevant scales (Inattentive
Symptoms, Hyperactive-Impulsive Symptoms, Total Symptoms or ADHD Index) on both
the Self-Report and Observer versions of the CAARS.

2. for Control Groups: T-Score < 60 on all of the DSM-IV relevant scales
(Inattentive Symptoms, Hyperactive-Impulsive Symptoms, Total Symptoms or ADHD
Index) on both the Self-Report and Observer versions of the CAARS.

5. never smoked an entire cigarette; no tobacco exposure in past 3 years.

6. expired air CO level < 3 ppm; plasma nicotine levels < 5 ng/mL.

7. cognitive functioning > 80 as assessed by the Kaufman Brief Intelligence test, Second
Edition(KBIT-II).

Exclusion Criteria:

1. history of chronic/significant medical condition.

2. current or past 12 month use of prescription medications for ADHD group.

3. meets criteria for any other Axis I Disorder (determined by the Structured Diagnostic
Interview for DSM; SCID) other than nicotine dependence that is significantly
impairing and would contraindicate participation in the present study.

4. meets criteria for any Axis II Disorder.

5. current substance abuse or dependence or history within the last 12 months; expired
breath alcohol level > 0.0; Positive urine drug screen for any of the following:
cannabis, amphetamines, opioids, benzodiazepines, barbiturates, cocaine.

6. inability to understand written and/or spoken English language.

7. reported uncertainty about being able to remain a nonsmoker in the coming year.