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The Science of Addiction

A multidisciplinary team of researchers at UB tackles substance abuse from all sides

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Story by Sonya Collins | Illustrations by James O’Brien

Why is food so good?

Why do we enjoy sex?

Our brains are hard-wired to reward us for doing the things that keep us alive and thus help continue our species. The reward? The release of a feel-good chemical called dopamine, which contributes to the pleasure that life-sustaining activities like eating and sex bring. Even the smell of a newborn baby stimulates the release of dopamine—at least in women’s brains it does—a reward that could motivate them to love and care for the baby, sustaining its life as well.

Dopamine neurons release dopamine into the synapses—the space between neurons. The pleasure-giving elixir then attaches to receptors on the receiving neurons. You feel pleasure, then other cells clear the dopamine away. You’ll have to perform one of those activities again to get another reward. That’s why you keep nourishing yourself, keep reproducing and keep taking care of those kids.

So what happens when that innate reward system doesn’t work the way it should?

It could be fertile ground for addiction, say scientists at UB’s Research Institute on Addictions (RIA). Research scientists at RIA, founded in 1970 as a part of the New York State Division of Research of the Department of Mental Hygiene, have contributed to scientific understanding of addiction for 46 years and counting. Since joining the university in 1999, the institute has received more than 150 grants totaling more than $140 million. Researchers brought in more than $5 million in grant money from the National Institutes of Health just this summer.

A national leader in substance-abuse research, RIA brings together some 30 research scientists in psychology, sociology, neurology and numerous subspecialties thereof. Multidisciplinary collaboration is the driving force behind RIA’s work. “It’s unique to have that expertise all in one place, where you can utilize all these skills leading to strong collaborations, rather than be limited to one area of expertise,” says Peter Thanos, a neuroscientist at the institute. “Having that capability is very helpful, fruitful and ultimately critical for research.” That research spans the psychosocial, neurobiological and genetic mechanisms of addiction, whether it’s addiction to substances like alcohol and drugs or to behaviors like gambling.

Pooling their diverse expertise, the scientists examine all types of addiction from initiation to recovery—from what makes a person prone to becoming addicted to whether it can be prevented and whether treatment works.

A broken reward system—why some people get hooked and others don’t

RIA director Kenneth Leonard

RIA director Kenneth Leonard

Your reward system—formally known as the dopaminergic system—gives you the drive to eat, reproduce and care for your children. And it makes you feel good for doing so. But just like a congenital heart problem or other birth defect, a person can be born with a faulty reward system.

One reason this could happen is a specific gene mutation that causes a shortage of properly functioning dopamine receptors. As a result, those typical pleasure-giving activities don’t bring as much pleasure. This can drive you to seek that pleasure fix through other activities. Research has shown that people who have this gene mutation have a higher risk than others for alcoholism; cocaine, heroin and marijuana abuse; smoking; and gambling and sex addiction.

What’s more, drugs themselves can interfere with the reward process. Cocaine, for example, latches onto dopamine receptors and blocks them, preventing that crucial clearing away of dopamine. That means the chemical then builds up in the brain and causes a high. Add a drug that amps up the brain’s reward system to an already faulty system, and addiction is even more likely to develop.

“Any drug that makes it into the brain is going to cause a reaction,” says RIA director Kenneth Leonard. “Over time, the brain itself and the way it works change.”

You can be born with a faulty reward system even if it wasn’t written in your genes—by being exposed to alcohol or drugs before birth. Research conducted by Roh-Yu Shen, a neuroscientist at RIA, has found that the brains of rats exposed to alcohol in the womb are similar to the brains of rats that use a lot of drugs but did not have any prenatal exposure. The similarities lie in the reward circuitry. “The brain-reward circuitry of the prenatal-alcohol-exposed animals has already changed to a state that’s similar to that in rats with repeated use of drugs,” Shen explains. “They’re already susceptible to drug addiction. All you need is the availability of drugs.”

Putting that theory to the test, Shen and her research team made amphetamines—think speed, uppers, crank—available to rats. Sure enough, the ones that were exposed to alcohol in the womb worked harder to get the amphetamines than their rat peers without alcohol exposure. And they also took more of the drug than the rats that weren’t exposed to alcohol in the womb.

But a mother who does not drink alcohol during pregnancy may still have a child with a brain wired for increased substance-abuse risk. Shen’s research shows that exposure to chronic stress in the womb can have the same effect on the brain as exposure to alcohol or drugs. “It could be any adverse life event during pregnancy,” she says. “Even a stressful or high-risk pregnancy could cause these brain changes in the womb.”

The first hit

Rina Eiden, RIA Developmental Psychologist

Rina Eiden, RIA developmental psychologist

While a genetic mutation or brain circuitry might lay the groundwork for addiction, you still have to take that first drink or that first hit. Some people are never tempted to touch an addictive substance and thus never learn whether their brains were wired to get hooked. Yet others might experiment with alcohol or drugs the first time they’re offered.

But why? What’s the difference?

One risk factor for becoming a substance abuser, research suggests, is having an alcoholic father. In fact, children of alcoholic fathers are at increased risk for violence, victimization, depression, anxiety and a host of other problems, too.

Rina Eiden, a developmental psychologist at RIA, wanted to find out what was happening in the lives of these children that pushed them to underage drinking or drug use—or didn’t. She tracked a group of more than 200 children for about 20 years, from the time they were 12 months old through high school. About 120 of the kids had an alcoholic father while the other 100 did not.

Across the cohort of kids, parenting at key stages of development played a crucial role in what became of the children, whether or not their fathers were alcoholics.

First, children who received ample warmth and sensitivity from their mothers, particularly when they were toddlers, were less likely to go on to abuse drugs and alcohol. “However, mothers whose partners were alcoholics were less likely to show that warmth and sensitivity toward their children during play interactions,” Eiden says. This led to higher rates of drug use and underage drinking among the children of alcoholic fathers.

Kids in both groups were also less likely to use alcohol or drugs when their parents monitored their activities. These were the parents who asked their kids things like, “Where are you going? Who are you going with? Are any parents going to be there?” Again, the difference was that parents were less likely to do that sort of monitoring in families where the father was an alcoholic.

“It’s not ‘Do you know where your teens are?’ like we see in the media. It’s ‘Do you know where your child is?’”
Rina Eiden, RIA Developmental Psychologist

Interestingly, Eiden found that it was important to start monitoring earlier than one might think, in late elementary and early middle school. “It’s not ‘Do you know where your teens are?’ like we see in the media. It’s ‘Do you know where your child is?’” Eiden says. “When parents didn’t monitor activities in the pre-adolescent period, children were more likely to hang out with delinquent and substance-using peers in early adolescence, and they were more likely to use alcohol as adolescents.”

Kids whose fathers were both alcoholics and depressed were also more likely to follow a path to substance abuse. “These kids had more behavioral problems, so they tended to seek out peer groups with similar problems, and this led to substance abuse,” says Eiden.

For about 17 years the psychologist has been following another group of children—now teenagers—whose mothers used cocaine during pregnancy. Here again, parenting quality and a stable, supportive family environment mitigated many of the behavioral effects of prenatal exposure.

About 30 to 40 percent of the kids ended up in foster or kin care by the time they were in kindergarten. Biologically speaking, these kids were the ones who would have been most vulnerable to the consequences of prenatal cocaine exposure because they had been exposed to the greatest quantity. But Eiden found that the kids raised in foster or kin care—and therefore not by a mother who used cocaine—had similar levels of attention-, aggression- and conduct-disorder problems as kids who were not exposed to cocaine.

This isn’t to say that more children should be taken from their mothers and put into foster or kin care. “It means pregnant, substance-using women really need help, both during pregnancy and after their children are born,” Eiden says.

Eiden’s work also suggests that while gene defects and faulty wiring could form the foundation for substance abuse, parenting can build a pretty strong foundation against it. No one, says Eiden, is predestined at birth to a life of addiction. “What happens to them after they are born is critically, critically important.”

The results of Eiden’s studies could help researchers, policymakers and public health professionals design more effective alcohol- and drug-abuse prevention programs. And, says Leonard, delaying substance abuse for even a few years can make all the difference. “Sometimes all prevention does is forestall [substance use],” he explains. “But if we can forestall it until people get older, drugs and alcohol may have less of an impact. People may engage in heavy alcohol use once they’re in college, but if they start then, they’re more likely to stop. That’s very different from starting to drink in middle school.”

Fighting a biological craving

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Still, prevention won’t work for everyone. More than 22 million people over age 12 needed treatment for alcohol or drug abuse in 2014. Among those who get treatment for alcoholism, only about one in four manage to quit drinking completely. This points to a need for more effective treatment.

Treatment programs like the ones we see in the movies involve locking a person away for some time and thus eliminating any access to substances. But simply confining the substance abuser for a short period of time in a sterile rehabilitation environment is not a cure for addiction, says neuroscientist Thanos. Addiction is a chronic relapsing brain disease. His work suggests that some people, when treated for one type of addiction, may simply swap it for another because the underlying causes of addiction have not been addressed.

The scientist took notice when bariatric surgeons began reporting that some of their patients were starting to show classic signs of substance abuse after gastric bypass surgery. That’s a weight loss surgery that reduces the size of your stomach in order to limit food intake. Bariatric surgery typically takes place in middle age, whereas, Thanos says, “peak incidence of alcohol and drug abuse occurs in the teenage years or younger adulthood.” So why were people suddenly getting hooked on alcohol, drugs, shopping, gambling and sex after bariatric surgery?

“One hypothesis,” says Thanos, “is that when people have what we refer to as reward deficiency syndrome, and you take away their ability to experience reward from food, some of those people may switch after surgery to another type of reward.”

He tested that hypothesis in his research on obese rats. Earlier research had shown that some rats and people drank more alcohol after this surgery. But in those studies it wasn’t clear why. Was alcohol suddenly more rewarding to the brain? Or did stomach malabsorption caused by the surgery mean people and rats had to drink more to get the same effect they used to get from less alcohol?

To rule out absorption as a factor, Thanos and his colleagues set up an experiment in which obese rats had to work to earn alcohol that was delivered by IV, bypassing the stomach altogether. In the experiment, rats who had gastric bypass surgery worked more for alcohol than their obese peers who had not had the surgery. As Thanos suspected, absorption wasn’t the problem.

In his current and future research, Thanos will investigate the possible neurological causes of the phenomenon. Using state-of-the-art neuroimaging methods, he is looking at mapping the brain’s response to food and alcohol cues in these subjects to determine if there is a difference in brain function when presented with sensory cues of alcohol and high-calorie foods. Regardless of the cerebral underpinnings, Thanos’ work underscores the importance of treatment that addresses the biological cravings and the triggers that might drive a person to relapse or abuse a new substance.

Retraining the mind

“The more we can do to provide our clients with coping skills, the better their prospects for recovery.”
Gerard Connors, RIA Clinical Psychologist

“One of the strongest factors associated with not relapsing is having coping skills,” says Gerard Connors, a clinical psychologist at RIA.

Connors researches treatment for alcoholism and prevention of relapse. Coping skills, he explains, include learning to handle both the internal and the external triggers that might drive you to drink, use drugs or engage in another compulsive behavior. Internal triggers are emotions like anger, frustration and sadness. External triggers might be the friends you used to drink with or the situations in which you usually drank. Both types of triggers can lead to relapse.

Looking at all of those triggers under the larger umbrella of stress, Connors is exploring whether mindfulness-based stress reduction (MBSR) might help. MBSR, developed by Jon Kabat-Zinn, professor emeritus at University of Massachusetts Medical School, is a meditation- and yoga-based practice intended to help practitioners cope with stress, pain and illness. In scientific research, MBSR has brought benefits to people with cognitive disabilities, chronic pain and chronic conditions from depression to diabetes, as well as to survivors of a number of cancers.

“MBSR gives people space to better cope with their world, whether it involves discomfort, stress, interpersonal conflict or addiction,” Connors says.

Connors’ research, still in progress, examines the benefits of adding MBSR to standard treatment for alcoholism, which typically includes counseling and a 12-step program, such as Alcoholics Anonymous. Participants in Connors’ study, in addition to receiving standard treatment, attended either a series of health and lifestyle lectures or a series of MBSR training sessions. Those who attended a greater number of MBSR sessions spent more days abstinent from alcohol in the following year than their peers who attended a comparable number of the lifestyle lectures.

“When people become more mindful,” Connors explains, “they’re more aware of situations that potentially pose a risk for a return to drinking. In the past, they might have quickly reacted by drinking. Now they can put some space between the [triggering] event and the reaction, and instead act upon it in a way that doesn’t involve drinking.”

His research, he adds, is “yet another indication that the more we can do to provide our clients with coping skills, the better their prospects for recovery.”

Looking ahead

In its 46 years in operation, RIA has contributed substantially to what we know about addiction. But many more questions remain. For example, we know that addiction to any substance or behavior is driven by compulsive behavior and the way that behavior changes the brain when it’s repeated again and again, but what if the person goes through an extended period of sobriety? “Does the brain go back, or is it always different?” asks Leonard.

Complicating matters, Leonard adds, is the fact that “the specific nature of that brain change differs from one drug to the next.” That means that alcohol causes one type of change, cocaine another, and opioids like heroin and prescription pain killers yet another.

With addiction to the latter reaching epidemic levels, RIA is currently expanding its research into that area—a new focus that will surely answer many questions, give rise to new questions, and fuel many more years of investigation.

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Sonya Collins is an Atlanta, Ga.-based independent journalist who covers health, medicine and scientific research.