Dr. Richard Schottenfeld of Yale University School of Medicine in New Haven, Connecticut, has begun enrolling patients in a clinical trial that is large enough to establish more definitively than previous studies whether disulfiram reduces cocaine abuse in opiate-addicted patients being treated with buprenorphine. About 180 patients are expected to participate in the trial.
"We want to get more people abstinent from cocaine and see them stay that way while they are on the medication," Dr. Schottenfeld says. "We're also doing some genetic subtyping to see if we can get more data on whether disulfiram reduces cocaine use by blocking the enzyme called dopamine-b-hydroxylase (DBH) that metabolizes dopamine," he says. "If disulfiram is working this way, it should work best in the people who already have low DBH activity because of their genetic makeup. If such a gene-medication interaction occurs, it will give us important information about who is going to respond better to the medication or even what the proper dose should be."
Getting this additional genetic information won't prove that disulfiram is working to reduce cocaine use through DBH, Dr. Schottenfeld emphasizes. "It will help us to better understand the mechanism through which this medication works," he says. "While disulfiram is great in a lot of ways, it affects many systems and we may run into unwanted side effects with it. So, if we find more evidence that it works through this DBH mechanism, maybe ultimately we can find a medication to target that mechanism more directly."