Sunday, December 23, 2007

Social theory leads to trial of possible anti-cocaine tool

LITTLE ROCK, Ark. — Cocaine users often chase away the taste in their throat or level off the high with beer or liquor, so researchers at the University of Arkansas for Medical Sciences thought small doses of a drug that targets alcoholics might help.

It didn't.

"We actually found the lower doses ... will exacerbate cocaine use," said Dr. Alison Oliveto, head of the study. "It will make cocaine use worse."

Oliveto and researchers are conducting a second study to examine the drug disulfiram's effect on cocaine and habitual opiate users, convinced by prior studies that something about the 1940s alcohol treatment may work at a metabolic level. But it was cultural experience, rather than empirical research, that first led doctors to think it might work.

Disulfiram, known as Antabuse in its brand-name form, has been used to help treat chronic alcoholics since its discovery. The drug requires patients to remain utterly abstinent from alcohol, even in its common forms.

"If you ingest alcohol in any form, we're even talking about wearing perfume, it can set up a pretty nasty reaction," Oliveto said. "We're talking about vomiting, flushing, increases in blood pressure, nausea — just really kind of nasty. Obviously, it's sort of a negative reinforcement approach."

It wasn't until 50 years after the drug's discovery that doctors began looking at disulfiram as a means to wean cocaine users from their habit. Instead of attacking cocaine use itself, a doctor looked at what users did on the periphery of their cocaine use.

Oliveto said doctors determined that many drank liquor to accompany the drug, to smooth out their high while cutting back on the drug's harsh aftertaste.

"It was very indirect and really very behavioral," she said. "It's very novel."

Previous studies suggested that disulfiram, coupled with therapy, helped wean cocaine users away from the drug by increasing the unpleasant effects of the drug, including anxiety. Armed with that information, Oliveto began a clinical trial that used half or less of the drug's maximum dose on chronic cocaine and opiate abusers. Researchers drew blood from test participants, wanting to see how disulfiram affected patients' dopamine levels.

Cocaine interferes with the absorption of dopamine, building up the neurotransmitters in the brain to cause the drug's high. The idea, Oliveto said, was that maybe the disulfiram was stopping that buildup.

"It's not that we're making it up, it's sort of like we're putting the cart before the horse," she said. "Now we're trying to explain the mechanism."

But in the weakened dose, men, those with a certain lowered dopamine level and those who haven't abused alcohol in the past did more cocaine during the study, Oliveto said. She cited the fact the study included those who also abused opiates, more often than not prescription pain pills like Percodan or Hydrocodone. When she began the study in Connecticut while at Yale, most of the patients she ran into used heroin, while those in Arkansas used the pain pills.

Oliveto said a second study under way will include higher doses of the drug, as well as the potential of having just cocaine users take part. The tests will include genome typing as well to see if the different users have a genetic makeup making them more likely to respond to the disulfiram.

Despite the study's findings so far, Oliveto remains certain that disulfiram could provide chronic cocaine users a means to escape the habit.

"I think part of the issue is people seem to be very afraid of (disulfiram). I'm not sure I understand why and I'm genuinely perplexed. It's been around for 60 years," Oliveto said.

Associated Press Writer

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