Could narcolepsy wake-up drug fight cocaine addiction?

WASHINGTON - The hottest topic in cocaine addiction is another drug - a medicine already sold to wake up narcoleptics.

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

In addition to blunting cocaine's notorious cravings, modafinil 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 modafinil 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 modafinil will pan out.

But for Dr. Nora Volkow, director of 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 modafinil had kept him from getting high - and several other modafinil 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," says Dr. Charles Dackis of the University of Pennsylvania, who led a pilot study that suggested modafinil more than doubled addicts' chances of going cocaine-free for at least three weeks.

That study enrolled just 62 people, but the results were significant enough for 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 modafinil really does work.

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

Addiction specialists gave it a look because even though modafinil 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 modafinil didn't make cocaine worse, some users found the once-a-day pill blocked that high. "We didn't expect that at all," Dackis says.

-Potentially more important, he says, modafinil 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 and resist another hit.

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

"The effects on cognitive processes are very subtle, and very interesting," Vocci says - and that's the reason that of half a dozen medications being studied as potential cocaine treatments, the government's biggest emphasis is on modafinil.

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

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

Addictions in general rewire the brain, says Volkow, the NIDA director. Drugs cause a feel-good rush by increasing amounts of the brain chemical dopamine. The brain reacts by tamping down regular dopamine production, making users feel lousy between hits and setting up the cycle of addiction.

At the same time, the dopamine surge also creates memory circuits that eventually establish so-called "cue-induced cravings": If an addict passes the crack house or sees friends he did drugs with, his brain literally sends a strong impulse to use again.

"One of the strategies of course, in terms of treatment ... is how can we help recover the function of the dopamine system, so the person that's addicted can become sensitive to natural stimuli," Volkow explains.

Modafinil seems to affect chemicals that in turn regulate dopamine production, a different pathway than cocaine takes in altering normal dopamine, and thus one that might counter it, adds Dackis.

"You can't assume this is going to work," he cautions. But if it pans out, a drug that could help cognition instead of just numb cravings would be "a big benefit in treatment."