Cover Story:

ADDICTION:

INROADS INTO ADDICTION

PBS joins IU and the State of Indiana to tackle an epidemic

Shattering lives and unraveling families and communities, addictions and substance use disorders take a deadly toll. In 2016 alone, for example, over 64,000 Americans died from drug overdoses. That’s more than the number of people who died during the nation’s worst year of gun violence, the peak year of the HIV/AIDS epidemic, or during the entire Vietnam War. Annual financial costs of this epidemic are 3.5 times the annual expenditure on diabetes and 2.8 times that of cancer.

PBS Professor Brian D’Onofrio observes, “Many people in our society are just beginning to recognize how big a problem substance use is and, frankly, has been. Substance use deaths are increasing, but we have always had substance use deaths.”

How will society begin to solve this colossal, multi-faceted problem? IU researchers from diverse fields seized the opportunity to frame an answer in response to IU President Michael McRobbie’s Grand Challenge initiative, bringing together:

A public university intent on deploying the combined knowledge of its College of Arts and Sciences, Schools of Public Health, Informatics, Law, Nursing and Medicine;
A team of world-class psychological and brain scientists in PBS gaining critical insights into the science of addiction;
Strong partnerships with the governor, the State of Indiana, its largest health and mental health care organizations, legal system and social services.

The university subsequently committed $50 million to the project: “Responding to the Addictions Crisis,” the purpose of which is to prevent, reduce and treat addictions in Indiana, and serve as a model across the U.S. and elsewhere.

Front and center to the effort is PBS. Its chair Bill Hetrick is on the steering committee. Heading one of five scientific leadership teams is PBS neuroscientist Ken Mackie. Lead investigator of a major project supported in the first round of funding is PBS clinical science professor Brian D’Onofrio. Others will participate as the initiative unfolds.

Add to that the generosity of an idealistic and entrepreneurial alumnus, David Naus (BA ’77) dead-set on tackling the long-misunderstood illness. Naus bestowed a $1.5 million major gift to establish an endowed chair in the science of addiction, which will enable the department to hire a first-class addictions researcher. ( More on this gift, here.)

“What our research is showing is that even before people are prescribed opioids, they have a lot of the problems that people are attributing to the opioids.”

-BRIAN D’ONOFRIO

Take a peek into a sample of this research, as it extends broadly across the axis of brain and behavior.

From the macroscopic perspective . . .

What are your chances of receiving a long-term prescription for opioid painkillers? You might be surprised to hear that it could depend on your mental health. As D’Onofrio and his close colleague Patrick Quinn in the School of Public Health have documented in large-scale population datasets, people with mental health problems, including substance use disorders, are more likely to receive long-term opioid prescriptions than those without these issues. As D’Onofrio explains, the conditions for which opioid painkillers are prescribed for extended periods, such as chronic pain and physical injury, are highly correlated with depression, anxiety and substance use disorders.

To alert doctors to patients most at risk for addiction, D’Onofrio and his collaborators at the University of Chicago are helping to implement an online screening tool that allows doctors to learn about their patients’ mental health problems. With the support of the Grand Challenge program, they are starting to test the new method in community settings around Indiana, from court systems to hospital emergency rooms to mental health facilities. The new project is part of a broader push to identify the characteristics of patients who are most susceptible to addiction.

. . . To the microscopic perspective . . .

At the level of neurochemical processes in the brain, neuroscientists Andrea Hohmann and Ken Mackie also investigate ways to reduce opioid addictions. They have identified neurochemical mechanisms capable of blocking the rewarding effects of opioids and have discovered a non-addictive compound that, in rodents, prevents both tolerance for and dependence on opioids. (See Taking Aim at Opiods for more on this research.) Their work also seeks “to harness the therapeutic potential of the brain’s own cannabis-like system to suppress pain without unwanted side effects of opioids,” as Hohmann explains.

. . . And everything in between

Mackie’s focus on the brain’s cannabinoid system has led him to collaborate with others seeking to discern the possible health risks of using marijuana at a time when states are debating legalization. Mackie and professors Brian O’Donnell, Sharlene Newman, Olaf Sporns, and Bill Hetrick have subsequently studied the effects of marijuana on the adolescent brain to find, for example, that adolescent users show changes in the communication pathways between brain regions.

Still other PBS researchers are making other important breakthroughs in understanding such critical features of addiction as relapse, which within four years affects 90 percent of those who undergo treatment, and the formation of substance use disorders in young adults:

For example, in one study with crucial implications for treating relapse, Professor Sharlene Newman built upon Professor emeritus George Rebec’s animal studies, to learn that the situational “cues” associated with cocaine or alcohol use, which trigger cravings, affect glutamate levels in the brains of humans addicted to alcohol, as well as rats.

It may be possible to scan people before they begin treatment to see if they’re likely to succeed.
Joshua Brown

Also addressing the problem of relapse, cognitive neuroscientist Joshua Brown has studied the brain activity of people with various forms of addiction. Based on his results, he suggests, it may be possible to identify those most susceptible to relapse before prescribing a particular treatment. “It may be possible,” he explains, “to scan people before they begin treatment to see if they’re likely to succeed. If you know who’s going to relapse, you know to take other measures, to allocate your resources differently.”

Taking on yet another critical angle on substance use disorders, clinical psychologist Peter Finn delves into the formation of these disorders in young adults, looking at “a range of people on a continuum some of whom may not have a substance abuse diagnosis, while in others it may be mild, moderate or severe.” His research explores individual decision-making with respect to alcohol or drug use and subsequently also seeks to develop and test forms of treatment that would lead to less risky decisions.

As PBS researchers make inroads into the elusive science of addiction, they are illuminating everything from entire populations to the individuals within them, from networks and systems in the brain to single molecules of which they are made. Their efforts, moreover, are propelling the larger university- and state-wide initiatives, seeing us closer to the end of our current crisis.