Initial studies by our laboratories suggest that nocturnal sleep regulation is abnormal in chronic cocaine users, and worsens further during periods of drug abstinence. To our surprise, these objective measures of initial poor sleep and subsequent deterioration during abstinence do not appear to be accompanied by any subjective perception of inadequate sleep or poor sleep quality (in fact, cocaine users perceive their sleep to be improved). Despite this perception of adequate sleep, subjects show deterioration in cognitive functioning across the two weeks of abstinence, similar to what would be predicted based on their deteriorating sleep. These findings become more important in light of Dackis and O'Brien's findings that the wakefulness promoting drug, modafinil, appears to be effective in greatly reducing drug relapse among abstinent cocaine users. Given modafinil's well-established efficacy in the treatment of excessive daytime sleepiness (EDS), as well as an emerging literature on cognitive enhancement (especially during states of sleep deprivation), we hypothesize that modafinil's clinical efficacy in the treatment cocaine dependence may result from the amelioration of """"""""occult"""""""" EDS that is associated with abstinence from the drug. The goal of the studies proposed here is to clarify the relationships between cocaine users' poor nocturnal sleep, poor daytime cognitive function, and modafinil's yet to be explained efficacy in reducing relapse to cocaine use. Despite their subjective sense of adequate sleep, we hypothesize that chronic cocaine users will demonstrate objective evidence of EDS (as measured by the multiple sleep latency test), and that modafinil treatment will result in improvements in objective measures of EDS and cognitive performance. Finally, in a pilot specific aim, we will test whether deficits in sleep and cognitive function predict the relapse to cocaine use during 3 months of follow-up (as well as whether potentially predictive symptoms are the same as those improved by modafinil). ? ? ?
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