We Are Addicts

By Suzanne Wu

Across USC, researchers are probing the mysteries of addiction, constructing a nuanced framework that challenges long-held conventional wisdom.

Jeffrey Hamilton/Getty ImagesJeffrey Hamilton/Getty Images

Like many researchers during their lean early years, Steven Sussman practically lived in the lab, sleeping in a chair on the nights he was too tired to make the 72-mile drive home. During one bad stretch – a grueling marathon session preparing a grant application – he was working 21 hours at a time and didn’t change his clothes for four days.

“I started to smell bad,” Sussman recalls.

He was a workaholic.

“Addicts aren’t just pathological hedonists,” Sussman explains. “Many are not particularly pathological or hedonistic.”

Now a professor of preventive medicine and psychology at the Keck School of Medicine of USC, Sussman earlier this year published an ambitious article in Evaluation & the Health Professions that sought to make sense of data from 83 studies about addiction. His conclusions were an eye-opening challenge to the idea that addicts are a rarity, the lunatic fringe. In a given year, Sussman found, 47 percent of the U.S. adult population will suffer from a severe addiction.

Almost half of us are addicts.

Sussman may even have underestimated. His study didn’t include coffee or smartphone use. It included workaholism, but, Sussman acknowledges, most addictions that don’t result in legal consequences or treatment records are difficult to track: If you are a young scientist in your 20s without a family to ignore, your problem might not be recognized, much less diagnosed. Similarly, addiction among retirees and older adults is likely underreported, according to the U.S. Department of Health and Human Services.

Of course, some addictions are more problematic than others.

“To the extent that people are harming themselves, I have less of a problem with [drug use],” says health economist Joel Hay, who studies the costs of legalizing substances such as marijuana. “But when you start to harm others, that’s when it affects the rest of us. Those are social consequences,” says the founding chair of the USC School of Pharmacy’s Titus Family Department of Clinical Pharmacy and Pharmaceutical Economics & Policy.

The repercussions of addiction are well documented – extending beyond broken relationships to accidents, lost productivity and health care costs. Alcoholism alone costs the United States an estimated $185 billion per year, according to the National Institute on Alcohol Abuse and Alcoholism.

Addiction, then, often is framed by policymakers not in terms of patterns of behavior but in terms of its aftermath – like a deeply personal form of disaster relief. How much damage was caused? Is your life in shambles?

But it’s hard to understand storm patterns by looking at the wreckage. Underlying the social harm caused by addiction is a more fundamental question: Why do so many people become addicts in the first place?

Scientists at USC are working across departments and campuses to identify the underpinnings of addiction – the piece of our inner workings that goes awry and leads us to self-destruct.

The more they discover, in conjunction with researchers across the country, the more it becomes clear that there’s no separate pathology for addiction – it’s bound up in who we are as humans. “We are all born with the systems of addiction,” says neuroscientist Antoine Bechara, professor of psychology at the USC Dornsife College of Letters, Arts and Sciences. “Addiction is a disease of decision-making and bad choices, just as there are diseases of memory. Addiction is the failure to learn from mistakes.”

What is addiction?

The American Psychiatric Association currently distinguishes between substance dependence and impulse-control disorders, such as compulsive gambling, sex or eating. In the organization’s Diagnostic and Statistical Manual of Mental Disorders (DSM), which serves as a guide for most clinical therapists and helps determine whether a treatment is likely to be covered by insurance, physical withdrawal symptoms are a key item on the addiction checklist. So, “psychological addictions” don’t count.

Alan Leshner, CEO of the American Association for the Advancement of Science and former director of the National Institute on Drug Abuse (NIDA), has long cautioned that hinging addiction on physical withdrawal is misguided and outdated, even within the category of substance dependence. It’s easy to see why. With some substances, such as alcohol, physical withdrawal symptoms are intense, even fatal; with other substances, such as marijuana, crack cocaine and methamphetamine, the addict experiences less severe physical withdrawal symptoms. Yet, these addictions are no less difficult to kick.

What do different kinds of addictions have in common? Literature has reinforced the idea that both substance and behavioral addictions tap into a core brain system: the mesolimbic pathway governing pleasure and reward. Unlike obsessive-compulsive behaviors, which are governed by anxiety, addiction is governed by nothing less than the pursuit of happiness.

As early as the 1950s, researchers at McGill University showed that lab animals receiving mild electrical stimulation directly to this part of the brain after pushing a button would thereafter push the button compulsively, ignoring water and food. Different addictions work on the brain in different ways, as biologist and USC executive vice provost Michael Quick has shown in his research on how recreational and therapeutic drugs alter the signaling properties of nerve cells. But they all appear to intersect at the mesolimbic pathway, which regulates behavior through a chemical called dopamine. Generally, dopamine binds with neuron receptors to produce feelings of pleasure, encouraging us to repeat certain behaviors again and again.

Biology and opportunity

“Addiction – the compulsive pursuit of pleasure – is, in a sense, evolutionarily adaptive. It’s not just crazy behavior,” says Adam Leventhal, director of the Health, Emotion & Addiction Laboratory at USC. “We are wired to want to feel good.”

Leventhal, assistant professor of preventive medicine and psychology at the Keck School, studies why some people become addicts after trying a substance just once, while others might have little susceptibility to certain drugs and use recreationally for years. In a sense, he studies moral luck.

“If the addictive personality is so harmful, why would it have been passed on from generation to generation?” Leventhal wonders. He points to people with impulsive tendencies, a trait that has a high correlation with addiction. Such people tend to think and act quickly, without considering long-term consequences. Impulsive personality types also tend to be extroverted and brave – the sort who are not afraid to talk to strangers. They have a gift for improvisation. They are creative. All desirable traits, in some settings.

The addictive personality, Leventhal says, “is an adaptive feature gone wrong in certain contexts.”

Just how much context matters to addiction has been the focus of Carol Prescott’s research for more than a decade. A professor of psychology at USC Dornsife, she seeks precision in the gray areas, examining how addiction is the result of both genes and opportunity – of nature and nurture.

There is plenty of conflicting data. On the one hand, Dana Goldman, director of the Leonard D. Schaeffer Center for Health Policy and Economics at USC, recently tied prescription drug addiction to rising Internet use. Goldman and a colleague at Massachusetts General Hospital found that states with the greatest expansion in high-speed Internet access from 2000 to 2007 also had the largest increase in hospital admissions for prescription drug abuse.

On the other hand, James A. Knowles, professor of research psychiatry and behavioral sciences at the Keck School’s Zilkha Neurogenetic Institute, found genetic causes for several psychiatric disorders, including addiction. Knowles was senior researcher on a 2007 study linking opiate addiction to the presence of chromosome 14q, a genetic predisposition much more prevalent among certain ethnic groups.

So which is it? Genetics or environment?

“It’s both, and that’s not a cop-out,” says Prescott, who is perhaps best known for her work studying substance abuse among twins. She has shown that in early adolescence, family and social environment is the most critical indicator of whether a child will try alcohol, cigarettes or marijuana. But once the brain has been exposed, there is more of a role for biology. By adulthood, the identical twin of a drug addict is much more likely than other siblings to be an addict as well.

Interestingly, though, the twins often are not addicted to the same thing. That could be a case of pursuing the same end by different means. “Certainly if the reason for substance abuse is self-medication, then different substances may serve similar purposes. Xanax can have similar effects to alcohol,” Prescott says.

There also may be such a thing as “addictive potential” in general – some underlying function that would put a person at risk for many addictions.

With the emergence of new research into addiction, the establishment position is starting to shift. A long-awaited revised edition of the DSM is scheduled for release in 2013. The changes under consideration for the fifth edition of the manual include grouping compulsive gambling with substance addictions. It’s a nudge toward a more inclusive idea of addiction and reflects the growing consensus that behavioral and substance addictions share common root causes in the brain.

“The more we understand about the biology of addiction, the more the lines among chemical, physical and psychological addiction begin to seem arbitrary and break down,” Leventhal says.

The NIDA already is funding studies of compulsive gambling that may pave the way for new insights into addiction. A gambler provides a model of an addicted brain, but one not affected by chronic drug intake.

At the same time, there’s a push to unify addiction research under one umbrella at the federal government level. Earlier this year, the National Institutes of Health, the primary U.S. government agency overseeing biomedical research, reviewed a recommendation that would merge disparate addiction institutes and parts of the National Institute of Mental Health to create one national entity for funding research on the causes of addiction.

“For those of us who study risk factors of addiction, this makes sense,” Prescott says. “It’s impossible to study the root causes of, say, alcoholism and not ask about depression or about other drugs. They’re too overlapping.”

Redefining addiction

A few years ago, neuroscientist Bechara, with Brain and Creativity Institute (BCI) co-founder Hanna Damasio and colleagues from the University of Iowa, found that smokers with lesions on a deep-seated, prune-sized part of the brain called the insula were able to quit smoking immediately, completely and easily. “My body forgot the urge to smoke,” one study participant said.

Nora Volkow, director of the NIDA, which funded the smoking study, called the findings “mind-boggling.” The New York Times said they were “likely to alter the course of addiction research.”

For decades, the insula, which exists in all mammals, was dismissed as a part of the brain with little to tell researchers about human consciousness – a dispatch center for primordial signals from the body’s nerve endings, alerting us to full bladders, empty stomachs and pain.

About a decade ago, a team of researchers from Newcastle University Medical School showed that people with insula damage had trouble understanding the emotional content of music. Even though their ability to hear was intact, they did not perceive music as music, only noise. Similarly, smokers with insula damage no longer wanted nicotine – smoking had lost its emotional edge.

The findings from the BCI are exciting. But think of this breakthrough another way, and it puts the challenge of kicking addiction in stark perspective: One of the most promising new directions we have for a cure is brain damage.

The growing realization that there is no separate brain pathway for addiction raises the possibility that we can’t treat harmful compulsions without affecting other behaviors we value. Would it be worth being able to easily quit smoking if the price were losing the ability to understand music?

“We happened to do the study with smokers, but we believe that the findings extrapolate to other addictions,” Bechara says.

Which brings us back to the problem of trying to cubbyhole addictions in terms of substance versus psychological dependence, ranking them by the strength of their withdrawal symptoms or prioritizing them by the damage they wreak on society. The more we know, the more the rules change.

In most psychological studies of typical human behavior, addicts have long been screened out for possible aberrant behavior. Not smokers. Simply as a practical matter, it would have been difficult a few decades ago to find enough nonsmokers to fill a study sample.

Thinking of addiction in terms of visible consequences also has played a role in separating smokers from other addicts. The immediate harm of having one more drink may be huge. The immediate harm of having one more cigarette is harder to quantify.

Over time, the scientific community has reconsidered these definitions.

“If you had asked me 40 years ago if smoking is an addiction,” Bechara says, “I would have said no. We didn’t know smoking was harmful then. But now we know it is harmful. Addiction is about persisting in a behavior despite knowledge of negative consequences.”

A disease of the will

In addition to exponentially increasing the likelihood of certain diseases through prolonged substance exposure, addiction has other long-term consequences. Volkow has shown that even after cocaine addicts are clean for a sustained period of time, there seems to be a permanent decrease in their dopamine receptors, making it more difficult for former cocaine addicts to feel pleasure.

Last year, professors Daryl Davies and Ronald Alkana of the USC School of Pharmacy identified a molecular ion “gate” in the brain that actually mutates when exposed to alcohol. Such brain changes have contributed to the compassionate characterization of addiction as a disease. Like many other diseases – skin cancer and hypertension among them – addiction is associated with voluntary choices that can, over time, interact with genetics and environmental factors, such as stress, to compromise our health.

Unlike other diseases, though, with addiction the symptoms burden the cure: Bad choices compromise our very ability to make choices. If addiction is a disease, it is a disease of self-destruction – as if people with skin cancer kept sneaking outside without sunscreen on cloudless days.

In 2009, Harvard psychologist Gene Heyman wrote Addiction: A Disorder of Choice, which challenges the idea that addiction is a disease, since it can be overcome by sheer will. Going cold turkey, and prevailing, is possible with addiction, yet inconceivable with other brain diseases, such as schizophrenia or Alzheimer’s.

It’s precisely the element of will that makes addiction such a poignant window on human behavior, says Drew Pinsky, clinical professor of psychiatry at the Keck School. Pinsky, more popularly known as Dr. Drew, started appearing on the syndicated radio show Loveline while still a medical student at USC, and now also appears on an eponymous talk show and three additional reality television shows. As the most prominent public face of addiction medicine, he has done more than anyone in the last two decades to deprive addiction of its greatest enabler: secrecy.

“Addicts are responsible for their own treatment,” Pinsky says, “but they are not responsible for the disease. I’ve never met an addict who was happy with being an addict.”

At USC’s Self-Control Neuroscience Research Lab, John Monterosso studies the denouement of the addiction narrative: how we sometimes say no, or, perhaps more accurately, no more. Just as researchers have isolated the brain’s reward mechanisms that spiral habit into addiction, Monterosso is approaching willpower as a matter of biology, not metaphysical strength.

“When people start talking about addiction as a ‘brain thing,’ they stop acting like people have control. It puts an upper bound on what humans are capable of,” says Monterosso, associate professor of psychology at USC Dornsife. But willpower, he notes, also is a “brain thing.”

Building off the large body of research into dopamine and reward systems, Monterosso examines which parts of addicts’ brains (he studies smokers and methamphetamine users) are active and which are suppressed when the addicts are trying to resist temptation. His work prompts the question of whether we will one day be able to bolster the parts of the brain that help addicts make better decisions.

“Yes, we are drawn to rewards, but we are able to control ourselves if there are consequences for seeking that reward,” says Bechara, one of the first researchers to examine the role of the prefrontal cortex in mediating decision-making. “There are areas in the brain that are in charge of this ability to self-control. It’s a new way of looking at addiction.”

Under the right circumstances, a rat will become addicted to almost any substance that humans might crave, be it sugar or nicotine. But animal models, Monterosso notes, only capture one side of the motivational struggle people experience. “Addiction is not just about seeking reward. It is about being conflicted,” he says. As humans, we have the capacity to make the big conceptual maneuver required for trading short-term pleasure for long-term goals.

Therein lies perhaps the most human aspect of addiction and the chance of weathering the storm of self-destruction. All animals have the capacity for addiction – humans included. But only humans get to participate in their own redemption narrative. We have it in ourselves to get better.

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