USC Researchers Work to Unravel the Riddle of Problem Drinking

DON’T PLAN ON just dropping by the new bar opening at the USC Health Sciences Campus next year. It will look, feel and sound like a real pub — complete with bar stools, genuine alcohol and TVs blaring sports— but it’s better described as a bar lab. Entry will require enrolling in a scientific study, and a visit will end not with last call but a blood draw at the clinic next door.

This scientific watering hole is part of the big plans from the new USC Institute for Addiction Science which brings together experts from across the university including the Keck School of Medicine, the USC Suzanne Dworak-Peck School of Social Work, the USC School of Pharmacy and other affiliated clinical centers to study and treat substance dependence.

Studying addiction and alcohol abuse has taken on increased importance: Data show a sharp increase in alcohol consumption during the COVID-19 pandemic, and habits have yet to return to pre-pandemic levels.

As public spaces reopen, researchers can start examining the short- and long-term consequences of this wave of increased drinking. Experience gives them a good idea of what to expect: Not everyone will respond the same way to excess drinking, but many will be susceptible to addiction, liver diseases or other problems.

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Support groups, rehab and medical treatments are available, but relapse rates can be high and medicines often have limited benefits. When it comes to liver transplants for the sickest patients, there aren’t enough donors for everyone who who needs those organs. Fortunately, USC researchers are working together on innovative approaches to better understand how people respond to alcohol and what medicines might be more beneficial to curb its harmful effects.

Alcohol Use Spiked During COVID-19 — But It Was Already High

Reaching for the bottle is a common response to a crisis; the same happened in New Orleans after Hurricane Katrina in 2005, for example. But people respond in different ways. John Clapp, a professor and executive vice dean at the USC Suzanne Dworak-Peck School of Social Work, says he drank a bit more during early lockdown when Zoom happy hours proliferated, but he soon returned to his regular habits.

“The novelty wore off,” he says. But for others, “it was basically like an endless weekend for a year and a half.” Some went the other direction: He notes that social drinkers often don’t enjoy drinking alone, and others worried (rightly so) that alcohol would suppress their immune system and make them more susceptible to COVID-19.

USC researchers reported in the Annals of Internal Medicine that on average, total alcohol sales increased by more than a third in the U.S. between April and June 2020. They also found that certain populations were especially likely to drink more, including parents of school-age children and members of minority groups. The former may have been suffering from a lack of childcare and the pressures of online school; the latter could have been stressed because they are more likely to have had to work outside the home, exposing them to contagion.

The effects are already apparent: Since June 2020, liver transplants for alcohol-associated liver failure have increased by more than 50% compared to pre-pandemic levels.

Now that pandemic restrictions have loosened slightly, some people may have returned to pre-pandemic drinking habits while others haven’t, says Jennifer Dodge, an assistant professor of research medicine and public health sciences at the Keck School of Medicine of USC. Further research on who’s at greatest risk for ongoing problems will be important for clinicians and policymakers, she adds.

In 2019, before the pandemic, nearly 15 million people in the U.S. had alcohol use disorder (formerly known as alcoholism). For people who aren’t dependent, occasional heavy drinking can still cause problems: The more alcohol we drink, the greater the effect on our brains. Over time, we need more booze to get the same buzz.

Some people can drink but will suffer few long-term consequences; others can’t. Genetics and environmental factors — peer pressure, availability of alcohol — can influence a person’s outcomes.

Daryl Davies, associate dean of undergraduate education and professor at the USC School of Pharmacy, knows firsthand about the scattershot nature of alcohol’s most damaging effects. As a teenager, he binged with friends. “I got lucky,” he says. “I outgrew it.” But some of his friends didn’t — and some have died because of alcohol or other substance use disorders.

The demographics of drinking are also changing. For women younger than 35, liver failure rooted in alcohol abuse has become an epidemic, says Brian P. Lee, a liver transplant physician and research scientist at the Keck School of Medicine. He points to anxiety and the stresses of family life as culprits for the spike.

Four cracked bottles set against a red background with sticker labels of a human body diagram.

The Science Behind Alcohol’s Effects on Your Body

As soon as you take a sip of wine or down a shot, alcohol gets to work. Its more immediate effects include facial flush, increased heart rate and blood pressure, reduced inhibitions, impaired perception in the brain and lower body temperature. Over the long term, it can increase risk for organ damage and cancer. Severe acute intoxication after binging can suppress brain, respiratory and cardiovascular functions, causing death.

Excessive alcohol consumption hits the liver hard, causing fat accumulation and inflammation, which can disrupt normal function. This can be exacerbated by a single binge (four to five drinks in two hours), says Hidekazu Tsukamoto, a professor of pathology at USC.

With repeated episodes of binge drinking, the liver may eventually build up scar tissue — known as cirrhosis — that prevents it from doing its job of detoxifying the blood. And signs of liver damage can be silent: “You don’t feel anything until you get really bad,” Tsukamoto says.

Alcohol causes similar damage to the pancreas, says Stephen Pandol, an associate director of the Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis. This organ, which creates enzymes needed to digest food and regulate blood sugar, suffers damage and scarring, leading to excruciating pain, malnutrition, diabetes and death.

Pandol oversees pancreas research at Cedars-Sinai Medical Center and is developing medications to prevent inflammation or reverse the damage. But both the liver and pancreas, he says, can reach a “point of no return” in which the disease progresses even if the person never drinks again.

Increased Alcohol Use Increases the Need for New Treatments

The first line of treatment for organ damage is to stop drinking, though physicians know that’s hard to do.

To break addictive behaviors, treatment options include counseling or support groups such as Alcoholics Anonymous. According to the National Institute on Alcohol Abuse and Alcoholism, about one-third of people who undertake some form of treatment are free of symptoms of alcohol dependence within a year; many others are able to reduce their drinking. AA and other 12-step programs are among the most effective approaches, according to a recent report in the Cochrane Library, a repository of systematic health reviews.

But cravings and withdrawal complicate recovery; about 90% of people relapse within four years of completing treatment, according to the National Institute on Alcohol Abuse and Alcoholism. “A 12-step program and a faith-based program are not for everybody,” adds Brian Lee.

What happens when AA or rehab isn’t enough? With chronic alcohol exposure, brain chemistry changes permanently, says Liana Asatryan, a research assistant professor at the USC School of Pharmacy. “Then the person actually needs to be treated with chemical means.”

Although a few medications exist, they are neither popular nor especially effective. Only 4% of people with alcohol use disorder use medication, and 70% of those patients relapse within a year.

For liver damage, there are further treatment options, but not great ones. Steroids may reduce inflammation, but they don’t work for everyone. The last shot is a liver transplant, but twice as many people are waiting for a liver as there are available organs, Lee says. There’s a huge unmet need for better treatments.

USC Seeks Better Treatments for Liver Damage

The first step toward better medicines is to understand, in greater detail, the effects of alcohol in the body. USC researchers in disciplines across the campus are collaborating to open these new paths of discovery.

Two USC centers are on the case. Since 1999, the Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis has directed funding to researchers around the region. It now supports nearly 60 labs, says Tsukamoto, the center’s director.

The center’s work includes supporting the research of Bernd Schnabl, a gastroenterologist at UC San Diego and associate director of the center. His team found a clue to alcohol-induced liver damage in the gut.

They discovered that when the gut contains too much of a certain kind of bacterium, a version of Enterococcus faecalis, a toxin is produced that enhances liver disease. If this bacterium and its toxin are present, a patient’s prognosis is more dire.

The solution may seem obvious — kill the bacteria — but it’s not that simple. When Liana Asatryan treated mice with antibiotics in her pharmacy lab, they had fewer bacteria in the gut, but drank more alcohol. She suspects that the antibiotics also decimated beneficial bacteria.

Schnabl is taking a more nuanced approach, experimenting with a virus that infects the problematic bacteria. This virus, otherwise harmless to animals, prevented liver damage in mice.

A New USC Center Studies Alcohol Dependence

The newest center is the USC Institute for Addiction Science, started in 2018 under John Clapp, Daryl Davies and Adam Leventhal, its director and a professor of population and public health sciences at the Keck School of Medicine. The goal, Clapp says, is to unite diverse faculty to study addiction in the lab but also in terms of human behavior — or as he describes it, “from cells to society.”

Already, the institute has more than 75 members across seven USC schools. Members treat patients with alcohol-induced problems, study how public policies influence substance use, and teach in USC’s addiction science minor. A master’s program is forthcoming.

Davies also has some ideas for medicines to prevent drinking or remedy its effects. One involves a family of drugs, including ivermectin, that have a long history as antiparasitic agents for conditions such as malaria. Studies show these molecules also reduce alcohol intake in mice.

Unfortunately, ivermectin doesn’t easily reach the brain, where it needs to be to squelch cravings. So Davies has found another compound to help. Dihydromyricetin, or DHM, has been used in China for centuries to treat liver ailments. It comes from the seeds and fruit of a buckthorn variety known as the raisin tree. DHM enhances the effects of ivermectin, but that’s not all. It also changes fat metabolism and boosts the breakdown of ethanol as it reduces inflammation, protecting the liver. The pair, or a similar combo, might find use as a hangover remedy, Davies says. But he’s more eager to use them to reach people with dangerously unhealthy drinking patterns, with the goal of reducing their urge to drink and thus protecting their livers.

After testing in his lab, Davies connected with Lee, the liver transplant physician, to run a small clinical trial of DHM in patients with liver damage from alcohol. They hope the treatment will diminish organ inflammation and damage.

Collaborating to Understand Alcohol Abuse

This kind of partnership is an example of the interdisciplinary nature of the USC Institute for Addiction Science. “That never would have happened without the institute pulling us together, people from different disciplines,” Davies says.

Other Institute projects, including the bar lab, will provide more opportunities for collaboration. While the bar lab exists only as a set of blueprints for now, Davies plans to test DHM’s effects on drinking behaviors there, too. It will be an important tool to bring the research out of a sterile lab and into a more realistic setting with the sights, sounds, smells and feel of a real bar.

Leventhal and Clapp also have plans for the bar lab. For example, if no beers on the menu exceed 5% alcohol by volume, do patrons’ preferences change? How do noise or light levels influence drinking? It’s possible to investigate these questions in real drinking establishments, Clapp says, but the bar lab will give the scientists greater control while saving on study costs.

These interconnected avenues of alcohol-related research at USC hold the promise of a better future for many people. And despite dire statistics about drinking and health, it’s not all gloom and doom, Leventhal says. “You can have full recovery,” he says, “and have a totally great life.”

Some of the studies featured in this article were supported by the National Institutes of Health (1RO1 AA022448-4, P50AA011999, P50AA011999, R01 AA024464, W81XWH1910888/PR182623)

When Should You Be Worried About Your Drinking Habits?

There’s nothing wrong with moderate drinking, which the CDC defines as up to one drink per day for women, two drinks for men.

Any more creates a greater risk of liver damage. Consider getting a screening for liver problems if you’ve ever been a heavy drinker.

If you or someone you know might have problems with drinking, reaching out to your primary care doctor is a good first step.

Other sources of information and help include:

This article was originally published in the Trojan Family Magazine.