In The Drinkers, painted by Vincent van Gogh in 1890, three men and a child huddle around a table as they glug down whatever’s in the pitcher in front of them. Their faces are focused, stern. Standing together, they still seem lonely, lost in the blues and greens the Dutch artist used to color them.
“They’re drinking because they’re unhappy,” says Adron Harris, the director of the Waggoner Center for Alcohol and Addiction Research at the University of Texas at Austin. Perhaps they’ve crossed over to what he and other neuroscientists call “the dark side,” a reference to how chronic alcohol-abuse changes the circuitry of the brain. The more a person drinks, the more their brain rewires itself to crave alcohol. Eventually, the brain may only pay attention to alcohol, even as relationships, jobs, and health fall by the wayside.
“It’s no longer facilitating human interactions. It’s no longer giving pleasures,” Harris says. “It’s simply trying to get back toward normal.”
Alcohol addiction is as destructive today as it was in van Gogh’s time, but Harris believes there now might be an ideal way to overcome it—one that we’ve created without even realizing it. New prescription drugs that could help addicts wean themselves off alcohol might already exist, he says; it’s just that they’re used to treat other conditions. Because the brain cells of an alcoholic have different genes turned on than the brain cells in a non-alcoholic, Harris wants to find prescriptions drugs that can be repurposed to turn off the problem genes in an alcoholic’s brain, effectively wiping it of withdrawal symptoms.
He wants a pill to stop alcohol cravings, and one that’s already available at Walgreen’s.
The Broad Institute of the Massachusetts Institute of Technology and Harvard University, where scientists research the genetic basis of disease, has created a library that catalogues the ways thousands of drugs change gene expression in the body. By looking at how these drugs affect genes in the brain, Harris has identified a couple that were promising in studies on animals. Within the year he hopes to start human trials. And, ideally, a new drug could be approved to treat alcoholism in several years.
There are already three prescription drugs that the Food and Drug Administration has approved to treat alcohol addiction, but just like a variety of factors can lead someone to abuse alcohol—genetic predisposition and access to liquor, for example—different drugs work well for different people. Harris wants the drugs he’s studying to provide alcoholics with more options. “We haven’t been successful in treating complex diseases because we try to target one thing. Really, we need to change the network of genes,” he says. “So rather than getting drugs that are very selective and do one little thing, in fact we need to look at drugs that have multiple effects in the brain.”
Developing a new drug can cost about $1 billion and take about 10 years, says Harris, so repurposing one that’s already on the market allows researchers to leapfrog over some checkpoints on the way to approval. Plus, he says, between cancer and other complex diseases, there’s not enough national interest in finding a cure for addiction right now, so the money to create a new drug to treat alcoholism just isn’t there.
That’s not to say alcohol-use disorder, the medical diagnosis for severe problem drinking, isn’t an enormous issue in the United States. “It dwarfs all other drugs, including illegal drugs,” says George Koob, the director of the National Institute on Alcohol Abuse and Alcoholism, one of the National Institutes of Health. According to Koob, excessive drinking costs the country about $250 billion a year. About 16 million people meet the criteria for moderate to several alcohol-use disorder, and about 90,000 people are killed every year as a result of alcohol, including fatal drunk-driving collisions and overdoses. Prescription-opiate addiction is an epidemic in the United States, but the number of people who die from prescription opioid overdoses is a sixth the number who die from alcoholism, according to Koob.
The first drug approved by the FDA in 1949 to treat alcohol-use disorder was Disulfiram, which increases the concentration of a toxic byproduct that occurs when alcohol is broken down in the body and causes nausea, which in turn can help some people avoid drinking. Two others, Naltrexone and Acamprosate, were approved in 1994 and 2004, respectively. But less than 20 percent of alcoholics get any treatment, and less than 10 percent get a prescription. Why?
“Presumably because they don’t know about it,” Koob says. Then there’s the stigma of alcoholism as a moral failing, and a lack of education in the medical community that prescription drugs are available. Even more may be soon. Several clinical trials are recruiting for Gabapentin, for example, a medication that’s currently used for a variety of disorders including neuropathic pain. The results will likely come out later this year, Koob says.
Still, a medication that works for one person might not work for another, he points out. That’s why scientists’ approach of harnessing a variety of pharmaceuticals to treat alcoholism is promising, says Barbara Mason, the director of the Pearson Center for Alcoholism and Addiction Research at the Scripps Research Institute: The more scientists understand about the neurobiology of the brain, the more possible targets there are to stymie the stress symptoms that come from chronic drinking. “I think there’s a lot of hope in the new strategies that are being developed,” she says.
Harris and his team think that at least part of the transition to the so-called “dark side” involves an inflammation of the immune system. If they can correct the inflammatory problems, maybe they can quiet cravings and reduce alcohol consumption, he says. But echoing Koob, he notes that effectively treating alcoholism could take a battery of prescriptions, plus some therapy. There’s just no silver bullet. He pointed to Alzheimer’s drug research as a cautionary tale. Unlike addiction, “a huge amount of money” has been poured into finding a cure. So far, the effort has failed dramatically.
“They’re beginning to ask if maybe because they were trying to target one thing with a very selected drug, they may need to have several drugs combined to work in Alzheimer’s patients,” Harris says.
He thinks the same is true of alcoholism.