Subjects participating in this protocol will participate in three phases: 1) pre-admission,
2) inpatient admission, and 3) follow-up. Pre-admission involves screening (detailed in
inclusion/exclusion criteria section) and one week of outpatient sleep and activity
monitoring. Inpatient admission is 16 consecutive nights on the Clinical Neuroscience
Research Unit and involves subjective and objective tests of sleep, sleepiness, attention,
and learning. During inpatient admission subjects will take modafinil or placebo. For
follow-up, subjects will return to the CNRU for one night and again participate in objective
tests of sleep, sleepiness, attention, and learning. We hypothesize that modafinil will
decrease subject and objective measures of sleepiness and will promote attention and
learning in cocaine dependent persons.
A relatively new treatment for the excessive daytime sleepiness (EDS) associated with
inadequate sleep is the drug modafinil. Modafinil decreases subjective reports and objective
measures of daytime sleepiness under conditions of sleep restriction, while enhancing
cognitive performance. At the same time, sleep quality does not appear to be affected
significantly. Interestingly, recent clinical trials in cocaine-dependent populations
suggest that modafinil reduces the relapse to cocaine use, by unknown mechanisms.
We propose to employ both subjective and objective measures of nocturnal sleep and daytime
sleepiness, as well as measures of general cognitive performance and sleep-dependent memory
consolidation, to explore potential mechanistic relationships between cocaine abstinence,
EDS, and modafinil's efficacy in preventing cocaine relapse.
The following specific aims are proposed:
Specific Aim 1: To establish whether objective measures of poor nocturnal sleep (e.g.,
reduced total sleep time and sleep efficiency) that progressively characterize periods of
sustained cocaine abstinence are also associated with objective evidence of excessive
daytime sleepiness (EDS).
Specific Aim 2: To establish the ability of modafinil to reverse the excessive daytime
sleepiness (EDS) and deficits in cognitive performance that characterize cocaine abstinence.
Specific Aim 3: To conduct a pilot study to determine whether the observed abnormalities in
objective sleep, EDS, and/or cognitive function predict relapse to cocaine use and/or
whether successful abstinence from cocaine is associated with normalization of the same.
- Male or female individuals, ages 18-65, meeting current DSM-IV criteria for cocaine
dependence. Documented positive urine toxicology screen for cocaine at intake and
regular 3 times more weekly use of cocaine.
- Subject has voluntarily given informed consent and signed the informed consent
- Able to read English and complete study evaluations.
- Use of prescription medication in the past 6 months indicating a medical or
psychiatric condition that in the opinion of the PI would interfere with study
participation (e.g. hypertension, severe renal or hepatic disease, HIV, primary
psychotic disorder, primary mood disorder, primary sleep disorder).
- Meeting DSM-IV criteria for dependence on any substance other than cocaine and
- Significant underlying medical or psychiatric conditions or hypersensitivity to
modafinil that in the opinion of the PI would interfere with study participation.
- Abstinence from cocaine for more than one week prior to inpatient admission.
- Positive urine or serum pregnancy test.
- Women who are pregnant or lactating, or not using a reliable method of birth control.
- (For subjects completing the fMRI portion of the study) Presence of or history
indicative of ferromagnetic metal in their bodies.
Peter T Morgan, MD, PhD
Peter Morgan, MD, PhD