Hundreds of cocaine users are testing whether that legal pill, called Provigil, could help them kick the addiction, and there’s early evidence that it may.

In addition to blunting cocaine’s notorious cravings, Provigil might also counter the damage that cocaine wreaks on users’ brain circuits — damage that, in turn, fuels the cycle of addiction.

The prospect of that double-whammy has the National Institutes of Health spending $10.8 million researching Provigil as a potential cocaine treatment.

Results from the first of three key clinical trials could arrive by year’s end.

Scientists are cautious.

In a hunt spanning two decades, no one has found a medication to help treat cocaine addiction, and there’s no guarantee that Provigil will pan out.

But for Dr. Nora Volkow, director of the NIH’s National Institute on Drug Abuse, the narcolepsy medicine tops the list of promising potential therapies.

It may help restore proper function of a crucial brain chemical, dopamine, that addiction hijacks.

And in describing why he’s hopeful, one leading researcher recounts the man who accused his drug dealer of selling bad coke before realizing Provigil had kept him from getting high — and several other Provigil testers who told of flushing cocaine down the toilet.

”I’ve been treating cocaine-addicted patients for something like 25 years, more, and I’ve never heard of anybody throwing away cocaine,” said Dr. Charles Dackis, of the University of Pennsylvania.

He led a pilot study that suggested Provigil more than doubled cocaine addicts’ chances of going cocaine-free for a period of at least three weeks.

That study enrolled just 62 people, but the results were significant enough for the NIH to fund new research — at Pennsylvania, the University of Texas in Houston, Boston University and other sites — enrolling about 650 cocaine users to see if Provigil really does work.

The main side effect so far: insomnia, not surprising as Provigil is sold today to help narcolepsy patients fend off that neurological disease’s sudden sleep attacks.

Addiction specialists gave it a look because even though Provigil isn’t a classic stimulant, it triggered something in the brain to also improve patients’ mood, energy levels and ability to concentrate — effects that might counter cocaine withdrawal. Then came the surprises:

Cocaine intensely stimulates the brain’s pleasure centers, producing not just a ”buzz” or a ”rush,” but outright euphoria. In a small safety study to ensure that Provigil didn’t make cocaine worse, some users found the pill blocked that high.

Provigil seems to increase activity in the prefrontal cortex, the brain’s decision-making command center and the spot that allows reasoning to override impulse or emotion. Cocaine reduces activity in that key brain region, making it even harder for would-be quitters to ignore cravings.

Provigil also increases the ability to think strategically, a means of weighing variables and risks to make decisions, says Frank Vocci, NIDA’s pharmacotherapy chief.

Cocaine is highly addictive: About 16 percent of people who try it become hooked.

In the latest data, from 2003, the government estimated that more than 1.5 million Americans were dependent on or abusing cocaine, and more reported recently experimenting with it.

Obstructive sleep apnea/hypopnea syndrome (OSA/HS) is a serious and chronic disorder characterized by repeated episodes of complete or partial collapse of the upper airway during sleep. The resulting disruption (or fragmentation) of sleep leads to excessive daytime sleepiness.

A relatively common condition, OSA/HS is estimated to affect 2 to 4% of middle-aged adults. Because the disorder has been associated with impairments in neurophysiologic, respiratory, cardiovascular, and cerebrovascular function, patients with OSA/ HS may experience significant morbidity and there is suggestive evidence of increased mortality.

Results from the Sleep Heart Health Study indicate that sleep-disordered breathing is associated with an increased risk for systemic hypertension, and prospective data from the Wisconsin Sleep Cohort Study demonstrate a dose-response association between sleep-disordered breathing at baseline and the presence of hypertension 4 yr later. Other studies have suggested that the incidence rates of occupational accidents and automobile accidents are increased in patients with untreated OSA/HS.

The use of Provigil for other conditions in which there is hypersomnolence has raised interest in its use for the treatment of residual EDS in patients who are receiving effective treatments for OSA/HS. To date, Provigil has been studied in two small pilot trials in patients with OSA/HS, albeit with different doses and designs from those of the present study. Both studies showed that Provigil improved daytime wakefulness but had no significant effect on sleep-disordered breathing or resting blood pressure monitored during the day. Neither study, however, assessed the efficacy and safety of Provigil in patients receiving nCPAP treatment. The present study was undertaken to evaluate the efficacy and safety of Provigil in the treatment of residual EDS in a large population of patients with OSA/HS who were effectively treated with, and regular users of, nCPAP therapy.

The results of the present study only support the use of Provigil as an adjunct treatment for residual daytime sleepiness in patients with OSA/HS who are effectively treated with nCPAP. In this trial, considerable attention was paid to patient selection and the monitoring of nCPAP effectiveness to ensure that the primary pathology of sleep-disordered breathing was appropriately treated. In contrast to the effective use of nCPAP in the prevention of OSA/HS disease progression and the resulting adverse cardiovascular sequelae, Provigil should never be used as a primary treatment of OSA/HS as it has no such anticipated beneficial effects.

In summary, the results of this trial suggest that 400 mg of Provigil taken once daily is an effective and well-tolerated adjunct treatment for residual EDS in patients with OSA/HS who are regular users of nCPAP therapy. The results further suggest that Provigil has no clinically significant effect on RDI, cardiovascular parameters, or nCPAP use.