Fighting a Deadly Foe

College researchers pursue the opioid epidemic on multiple fronts

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Last year was a peak year for drug overdoses in southern Indiana — particularly along Bloomington's iconic Kirkwood Avenue. “It was the worst year I've seen in my 31-year career in the police department,” recalls Bloomington Police Department Chief Michael Diekhoff (B.A. ’89, Criminal Justice). While those overdoses weren't solely the result of opioid use, dependence on the painkillers has become increasingly common.

What's happening in Monroe County mirrors a larger trend. A 2016 IUPUI report suggests that, since 1999, Indiana's rate of fatal drug overdoses has increased by 500 percent. Put another way, overdose deaths now supersede automobile accident fatalities. What's more, Hoosier deaths from opioid use were up by 111 percent between 2015 and 2016, according to State of Indiana Management Performance Hub statistical reports. And deaths due to synthetic opioids were up by 134 percent within the same period.

The scope and urgency of the problem call for a response that's both sweeping and concerted. Enter IU's “Responding to the Addictions Crisis” Grand Challenge initiative — and College of Arts and Sciences researchers singularly positioned to make a difference.

“We have the scientists who work on studying addictions all the way from the molecular level to the social-psychological level,” College of Arts and Sciences Executive Dean Larry Singell says. “If you look at the Department of Psychological and Brain Sciences, which is likely to be a major contributor to the grand challenge, they have faculty who look at models of addiction, how it works and what its impact is, and how you can address it at the cellular level.”

Opioid alternatives

Andrea Hohmann is a Linda and Jack Gill Chair of Neuroscience and a professor in the Department of Psychological and Brain Sciences. “With the current opioid epidemic," she says, "it's really become clear that there's an urgent need to find better treatments for chronic pain that are non-addicting and that are safe and effective.”

To that end, Hohmann and her colleagues have picked up where others have left off by testing new therapeutic indications for existing molecules. Hohmann and her team recently reported on such a drug, and her lab showed that this compound “was able to fully reverse established neuropathic pain in mice. Moreover, when we gave the drug repeatedly to animals, we did not see the development of tolerance,” Hohmann explains.

A billboard advertising treatment for opiate addiction stands on Highway 37 between Martinsville, Ind., and Indianapolis.

In a separate experiment, Hohmann’s laboratory noted reduced levels of opioid-induced tolerance and physical dependence in neuropathic animals that had been treated with the new drug. In other words? Animals treated with a combination of morphine and the new drug did not demonstrate a need for increased levels of morphine and showed lower levels of opioid withdrawal symptoms.

In collaboration with fellow Linda and Jack Gill Chair of Neuroscience Ken Mackie, Hohmann is working to identify individual pathways inside cells that are recruited in pain suppression. Identifying these signaling pathways could offer clues to this new drug's mechanics. Research associate Xiaoyan Lin, who performed the rodent studies, and assistant research scientist Amey Dhopeshwarkar, who performed the signaling studies, were key collaborators on this work.

“I think there's a lot more research that we would need to do before it could be evaluated in opioid users, but we think it's an exciting target,” Hohmann says. “We're hoping that this means that we may have a real opportunity to accelerate solutions to the current opioid epidemic.”

Identifying 'doctor-shoppers'

In lieu of working on the molecular level, still other College disciplines are looking at the addicted individual as a whole.

“They ask, 'What is the consequence of addiction?'” Singell says. “And they look at addiction at the psychological level. 'Clinically, what have you observed? What are the types of outcomes that happen when people are addicted?'”

To better understand the varied responses to mass opioid addiction, it helps to consider some of the epidemic's underlying causes. In part, the overzealous prescription of highly addictive opioid pain medications is to blame. The U.S. Centers for Disease Control and Prevention notes that, since 1999, painkiller prescriptions and sales have quadrupled, and by 2014, nearly two million Americans were either abusing or were already hooked on opioids.

“The government cracked down, because doctors had been prescribing them so freely,” Diekhoff explains. “So, they cut people off who probably had legitimate pain issues. And then they didn't have anywhere to turn, so they turned to illegal drugs like heroin. Also, the prices of drugs have come down, so it was just this aligning of everything that led to this.”

"We believe that who a patient targets for prescriptions may be more telling than how many prescribers are targeted," says Brea Perry, a professor in the College’s Department of Sociology.

The resulting drop in the number of physicians prescribing opioids swelled the ranks of “doctor-shopping” patients — those who visit multiple physicians in hopes of obtaining several opioid prescriptions simultaneously. Brea Perry, a professor in the College’s Department of Sociology, uses social network analysis of prescription claims data to detect doctor-shopping behavior.

“Doctor-shopping is a sign of escalating abuse and risk for overdose,” she says. “To date, doctor-shopping has been classified using crude thresholds calculated using the number of different opioid prescribers and pharmacies where opioid prescriptions were filled. These measures are prone to error, because low and moderate levels of abuse are undetectable.”

To complicate matters even further, Perry adds that terminally and chronically ill patients may be mischaracterized as doctor-shoppers.

“We believe that who a patient targets for prescriptions may be more telling than how many prescribers are targeted,” Perry says. “For example, a patient who systematically seeks opioids from three physicians who overwhelmingly prescribe to heavy opioid users is probably more likely to be a true doctor-shopper than a similar patient who seeks opioids from three random physicians.”

To determine how “active” a person is within the prescription network, Perry’s research team analyzes physician-and-patient prescription ties.

“Preliminary unpublished findings indicate that people who simultaneously meet traditional criteria for doctor-shopping and a network-based indicator of doctor-shopping are over 30 times more likely to overdose than those who meet neither criteria,” Perry says.

What's next? She and her colleagues will use machine-learning methods to determine whether their network-based indicators can successfully classify drug-seeking behavior.

“We hope network methods will be used more widely in the research and clinical communities to prevent or intervene in opioid abuse trajectories,” Perry says.

Harm reduction

Well-crafted policy is another weapon in the arsenal. And, although researchers continue to add to the body of evidence supporting best practices for mitigating opioid addiction, Indiana Recovery Alliance Director Christopher Abert says those findings don't always seem to inform Indiana statute.

“[The legislative] response has been mixed,” he says. “Some of them have been evidence-based and, in some sense, proactive measures [have been introduced]. And then we have punitive measures that are typically pushed by prosecutorial interests.”

“A 2016 IUPUI report suggests that, since 1999, Indiana's rate of fatal drug overdoses has increased by 500 percent.”
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Abert has seen proactive measures like needle-exchange and harm-reduction programs work first-hand. Established in 2014, Indiana Recovery Alliance is staffed by current and former drug users and is intended to empower drug users to make positive life changes.

“If someone is seeking abstinence, we'll bend over backwards to help them achieve that,” Abert says. “If they want medication-assisted therapy or if they just want to not die and not transmit disease — or avoid having diseases transmitted to them — then we will bend over backwards for that.”

In addition to providing sterile needles and connecting clients to various social service agencies as needed, the Bloomington-based nonprofit also offers doses of the overdose-reversal drug, Naloxone. “One thing we’ve already noticed is we've given out well over 20,000 doses of Naloxone — and we’ve had over 2,000 reversals reported back to us,” Abert says.

Of Indiana's 15 largest counties, the percentage of fatal overdoses has increased by about 45 percent on average, Abert notes.

“Except for two — Monroe County and Clark County,” he says. “Both of those counties have syringe service programs, which give out Naloxone directly to people who use drugs.”

Prevention, intervention

Ideally, caregivers would be able to identify individuals at high risk for opioid-addiction long before they develop intractable habits. A professor and director of clinical training for the Department of Psychological and Brain Sciences, Brian D'Onofrio is collaborating with computer-adaptive testing developers to help community partners better assess at-risk individuals.

“You have to have the appropriate interventions for people with substance use problems — or the appropriate preventative services,” he says. “But you can't intervene if you don't know who needs it or who needs it most. We know that there are a lot of psychological factors that predict people having later substance use problems.”

Among them? Attention-deficit/hyperactivity disorder (ADHD), depression, anxiety, and suicidal ideation to name a few. More accurate intelligence-gathering on these and other risk factors could help emergency departments, behavioral health centers, and others to provide individuals with the care they need.

“This is leveraging advances in statistics and measurements and computer software and technology to help numerous disciplines,” D’Onofrio says, “everything from general practitioners to psychiatrists to social workers to the criminal justice system. It is truly collaborative and interdisciplinary. We're taking the best advances that we have in science and trying to implement them to best serve the population of Indiana, the country, and, ultimately, the world.”

Susan M. Brackney

Susan M. Brackney holds a B.A. in English from Indiana University. A professional writer since 1995, she has written for Boy Scouts, stoners, interventional radiologists, would-be beekeepers, depressives, the one percent, and many other walks of life. Her work has appeared in The New York Times, Discover, Organic Gardening, Hobby Farms, and Indianapolis Monthly Magazine, among others. Brackney is also a member of the American Society of Journalists and Authors and has published four nonfiction books, including Plan Bee: Everything You Ever Wanted to Know About the Hardest-Working Creatures on the Planet. Reach her at writer@susanbrackney.com.