This study is being done to find out if medicines that affect a neurotransmitter (chemical
messenger) in the brain called adenosine improve behavioral problems that are related to
drug abuse. Another purpose of the study is to find out how genes related to adenosine
change how people respond to these medicines. More information about how these medicines
change behaviors may be helpful to come up with new treatments for drug abuse.
Aim 1. To characterize the behavioral and subjective effects of acute caffeine
administration in cocaine-dependent subjects, using laboratory measures of impulse control,
drug discrimination (with d-amphetamine as the training dose), and subjective effects.
Hypotheses related to Aim 1:
1. Subjects will show decreases in impulsivity (delay to reward and response inhibition)
after acute oral doses of caffeine compared to placebo.
2. Subjects will show some stimulant-like subjective effects following acute oral doses of
caffeine, but not the euphoric effects that would predict abuse potential.
3. Following training doses of placebo and 20 mg d-amphetamine, oral doses of caffeine
will be discriminated as being different than 20 mg d-amphetamine and different from
Aim 2. To determine the effect of a 2-week trial of oral caffeine on laboratory measures of
impulsivity and cue reactivity in cocaine dependent subjects.
Hypothesis related to Aim 2:
1. Daily caffeine (600 - 900 mg) treatment will decrease impulsivity (delay to reward and
response inhibition) compared to placebo.
2. Daily caffeine (600 - 900 mg) treatment will decrease cocaine related cue reactivity
compared to placebo.
Secondary Aim 1. To examine the effect of 2-weeks of treatment with caffeine on cocaine use
in cocaine dependent subjects.
Secondary hypothesis 1: Cocaine dependent subjects treated with caffeine will show a
significant reduction in cocaine positive urine drug screens compared with cocaine dependent
subjects treated with placebo.
Secondary Aim 2. To examine the relationship between gene polymorphisms for the A2A receptor
gene and behavioral effects of caffeine Secondary hypothesis 2: Genetic variation in the
adenosine A2A receptor gene (ADORA2A) will be associated with the behavioral effects of
- Subjects who currently meet DSM-IV criteria for cocaine dependence.
- At least one cocaine positive urine during screening.
- Current regular consumption of caffeine.
- Female subjects: a negative pregnancy test.
- Current or past DSM-IV Axis I disorder other than substance abuse/ dependence
- Any significant non-psychiatric medical illness requiring ongoing medical treatment
or which would preclude treatment with d-amphetamine or caffeine
- Substance dependence other than cocaine within the last 3 months.
- Positive breath alcohol.
- Positive urine drug screen for drugs other than cocaine or THC at the time of
- For female subjects: known pregnancy or a positive pregnancy test or current breast
- Diagnosis of Adult Attention Deficit Disorder as determined by: a) meeting DSM-IV
criteria for childhood ADHD, b) currently has impairing ADHD symptoms, c) ADHD
symptoms can not have remitted at any period since childhood.
- HIV positive.
- I.Q. below 70.