July 1, 2009 — Historically, the United States has shown itself to be as poorly equipped to deal with the consequences of alcoholism as some individuals are to deal with the effects of alcohol itself.

Temperance advocates saw alcohol dependence as a moral failure, urging alcoholics to sign pledges to reform. The 18th Amendment to the Constitution made alcohol illegal, prohibiting its sale, manufacture and transportation, only to be repealed 13 years later. More recently, society has viewed alcohol abuse as a behavioral disorder to be treated with therapy and 12-step programs.

In each case, there has been only limited success in reducing the social costs and preventing the personal tragedies caused by alcohol dependency. Today, there are still approximately 14 million people in the United States who abuse alcohol, and the financial repercussions of alcohol abuse – ranging from medical costs and lost productivity to harm to others – have been estimated to be $185 billion annually.

"Most people assume that addiction reflects a lack of moral willpower," said Dr. Bankole Johnson, Alumni Professor and chairman of the University of Virginia's Department of Psychiatry and Neurobehavioral Sciences. "However, there is a biological component of alcoholism – just as there is with diabetes or high blood pressure. Alcoholism is a disease of the brain."

While the idea of alcoholism as a disease gained currency in recent years, it was a metaphor in search of a factual basis. Johnson was instrumental in changing that. He is a world leader in researching the biological mechanisms of addiction and testing treatments that might interrupt them.

For his achievements, Johnson was honored with the Distinguished Psychiatrist Award, one of the highest honors bestowed by the American Psychiatric Association. He founded ADial Pharmaceuticals to translate his discoveries into treatments that are effective in helping people with alcohol dependence.

Alcoholism is now understood as an abnormality in the regulation of certain brain chemicals, especially dopamine. Dopamine is modulated by more than 100 neurotransmitters – and Johnson and colleagues Dr. Nassima Ait-Daoud and Ming D. Li have focused on the role of one of them: serotonin.

They have discovered that people with a particular variant of the serotonin transporter gene have a propensity for heavy drinking, and that ondansetron, a drug used to prevent chemotherapy-induced nausea and vomiting, is particularly helpful in treating these people.

For Michael Torok, chief operating officer of ADial, this combination of discoveries is particularly exciting.

"People have talked about the promise of personalized medicine," he said. "ADial has the means to deliver it."

ADial is seeking FDA approval for using ondansetron to treat alcoholism and is developing an inexpensive test to identify individuals who would particularly benefit from it.

ADial is also pursuing the introduction of a series of combination medications using ondansetron and two other drugs used to treat alcohol dependency, topiramate and naltrexone. Along with Ait-Daoud, Johnson conducted a series of pioneering studies that showed that topiramate – a drug currently used to treat seizures and migraine headaches – was highly effective in curbing alcohol consumption.

ADial's first dual medication, which combines topiramate with ondansetron, is expected to enter Phase III clinical trials in 2010, at which point it will be tested against standard treatments.

The treatments that Johnson and his colleagues have developed are not merely more effective than existing treatments; they are more likely to be adopted by heavy drinkers.

"One of the chief advantages of the treatments that ADial is developing is that individuals don't have to stop drinking to use them, as they do with current medications," Torok said. "Our treatments can help people stop or manage their drinking more effectively, not just keep them from drinking once they've stopped."

ADial's goal is to provide people with other choices besides complete abstinence or complete failure, improving their ability to function in society.

"One of the reasons I conduct my research is that as a physician and a scientist, I want to reduce suffering," Johnson said. "ADial is part of that vision."