UNO Magazine: Crisis Mode

The following story appeared in the most recent issue of the UNO Magazine, which highlighted the efforts being made by UNO alumni, faculty, staff and students to promote health and wellness. Read the magazine online as a Flipbookor download a PDF.

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In different ways, UNO professors, instructors and graduates are working to address what some have called an epidemic rivaling the AIDS crisis of the 1980s — opioid addiction.

Numbers paint a grim picture of its use and abuse in the United States. According to the Centers for Disease Control, 72,287 people died from drug overdoses in 2017, an increase of about 10 percent from the year before. Nearly 49,000 of those deaths was caused by opioids. With prescription and illicit opioids fueling the trend, an American now is more likely to die from a drug overdose than kidney disease.

A closer look reveals the human tragedy behind the statistics. A single mother on Medicaid puts her child at risk as addiction's grip gets tighter. A police officer is trained to administer the opioid antidote Narcan to counter the growing number of calls involving a possible overdose. A doctor faces the agonizing choice of whether to treat a patient's serious pain or avoid the risk of that person getting hooked on opioids.

“There are a lot of people out there in a lot of pain, and attempts to address that issue have contributed to this opioid crisis,” says James Zadina, a professor of medicine, neuroscience and pharmacology at the Tulane University School of Medicine. “We think we need better pain medications. We need some that don't create that addiction and this problem."

Decades-Long Search

Zadina received a bachelor’s degree in psychology from UNO in 1973. He went on to get his doctorate, become a researcher at Tulane and serve as director of the Neuroscience Laboratory at the Southeast Louisiana Veterans Health Care System.

For more than two decades, he has been on the hunt for a better way to treat pain.

His first breakthrough came in 1997, when Zadina led a team that isolated a naturally occurring neurochemical that rivals morphine’s pain-killing ability — but without the addictive quality. Like morphine, the natural compound binds to what’s known as the mu receptor in nerve cells, blocking the brain’s ability to pick up the body’s pain signals.

Zadina set out trying to modify the chemical, which was named endomorphin. He wanted to develop analog versions that would be useful as medication.

“We started this before there was a lot of attention,” Zadina says. “It’s taken on more urgency now.”

Nearly 20 years later, opioids are part of a national discussion, with nearly 50 deaths a day attributed to overdose of prescription painkillers. That’s not even including heroin deaths, which increased in some areas where addicts sought cheaper alternatives to prescription drugs.

Zadina says the human toll is never far from his mind as he continues to search for a safer alternative to opium-based painkillers.

“If you watch the news every night, you see the potential impact,” Zadina says. “It's always on your mind that you want to move forward.”

He is moving forward, and might very well have a solution that could end the opioid crisis.

But more on that later.

Legal Issues

The impact of opioid abuse extends beyond the medical laboratory. UNO graduate Joe Jeanette works on an opioid task force in Nebraska that includes treatment providers, medical professionals, law enforcement and prosecutors.

Jeanette says opioid abuse is different from other types of drug use in that morphine or Vicodin, unlike meth or cocaine, has a legitimate medical use in some instances.

“What it boils down to is meth, coke, crack cocaine, right off the bat it’s illegal. That makes it easier,” says Jeanette, law enforcement coordinator for the U.S. Attorney's Office in Nebraska. “With opioids, we’re looking at a lot of people that have had surgeries that got them down that road. Are we going to lock them up? I don't think so.”

Jeanette received his bachelor’s degree in criminal justice from UNO and teaches a course on the subject at the university. He still approaches the problem from a law enforcement perspective.

“We have aggressive prosecution on the federal side,” he says. “It’s No. 2 behind guns and gun violence at the Department of Justice.”

Strong policing is necessary, he says, especially when an illegal supply of the powerful synthetic opioid fentanyl is intercepted.

But he believes the broad scope of the problem requires a solution that includes drug courts, new options for pain management and even training law enforcement officers to administer a version of the opioid antidote naloxone to restore normal breathing during an overdose.

While some have expressed concerns about addicts seeing how much of a drug they can ingest before needing an antidote, Jeanette believes the vast majority in law enforcement see EMT training as fitting with their mission.

“We’re out there to save lives, and this is part of it,” he says.

Jeanette’s push with the task force is to strengthen state law for prescription drug monitoring. He wants to allow law enforcement limited access to a database to see who might be doctor shopping for prescriptions, though this has drawn opposition on privacy grounds.

Jeanette and other supporters of this proposal fear that Nebraska could become attractive for all the wrong reasons without closer monitoring of prescription drug purchases.

“Our concern is once these other states start cracking down, we're open game here,” he says.

'All Hands on Deck'

One of the worst states for opioid abuse was Florida, where UNO professor Tara Richards conducted research into the drug treatment needs of the Medicaid population of that state.

Her research, conducted from 2009 to 2012 while she was pursuing her doctorate, came about just as Florida became known for its “pill mills” and opioid addiction was becoming a national problem.

She is now an assistant professor in UNO’s School of Criminology and Criminal Justice. She says UNO is positioned to make an impact on this issue because of the university's focus on public service in both urban and rural areas.

“Opioid addiction touches every aspect of one’s life,” she says. “It impacts their ability to parent. It impacts their ability to work. It impacts their health care usage. It’s is not just a problem that is interesting to psychiatrists and medical professionals. This is an all-hands-on-deck issue.”

Richards says her research found that the low-income Medicaid population faces obstacles to affordable substance abuse treatment. Sometimes, she says, basic transportation can be a problem, with methadone clinics open at inconvenient hours and some located as far as 100 miles away for people living in rural areas.

“Broadly speaking, individuals on Medicaid have more complex physical and mental health issues,” she says. “If you are someone with limited means, you have limited access to health care, including substance abuse treatment.”

Opioid addiction strikes all income levels, but Richards says the low-income population would benefit if the problem was viewed more as a sickness than a weakness.

“Individuals with opioid addiction are filling our courts. They are getting arrested,” she says. “We have to make a concerted effort to reduce the stigma of seeking treatment.”

She also says low-income Medicaid patients have fewer options for non-opioid pain relief, which increases the possibility of addiction down the road. Solving the problem of opioid addiction, she says, includes better access to other types of pain relief, from exercise to acupuncture.

“There are very few options for individuals seeking services through Medicaid for non-medicinal treatment,” she says. “Those things are not available to a low-income population.”

Jeanette says the benefits of alternative pain management aren't lost on the task force examining opioid abuse in Nebraska. “We're doing a good job of educating our medical students and pharmacists on the alternative to pain medications,” he says.

Zadina's Morphine Alternative

The best alternative could be medication that stops pain without causing addiction in the first place. In his laboratory in New Orleans, Zadina is getting closer to a major development.

In 2016, Zadina published a paper describing an analog of endomorphin that treats pain as effectively as morphine, but with reduced side effects such as addiction liability, tolerance and respiratory depression.

With today's prescription opioids, a patient sometimes takes higher doses as the body develops tolerance. This increases the risk of addiction, while respiratory failure is what ultimately can lead to death from overdose.

In the study, rats were given a chance to press a lever that administers more morphine. Much like a human addict, they pressed and pressed, illustrating the addictive nature of that drug.

Zadina's new drug? It didn’t generate the same lever-pushing response — but it still relieved the pain.

“That’s kind of exciting,” Zadina says.

The next big steps will involve clinical trials in humans. Zadina found a commercial partner to oversee studies for FDA consideration.

The process could take up to seven years as studies assess the drug’s effectiveness in humans while looking for possible drawbacks, such as harm to the kidney or liver. The upsides are huge, with MIT's Technology Review magazine describing Zadina's discovery as having the potential to produce “the painkillers that could end the opioid crisis.”

“We have to see what it can do in humans,” Zadina says. “You never know. A lot of drugs do well until the very end. The first thing you have to do is make sure it doesn’t hurt anybody.”

In some ways, painkilling drugs have changed little since World War I. The active ingredient in Vicodin, now the most prescribed drug in the country, was developed 100 years ago. The same goes for oxycodone and hyrdocodone.

“We keep doing the same things and expecting different results,” Zadina says of past approaches to pain management.

On the trail of this new drug for more than 20 years, Zadina believes significant change is coming, It just might seem painfully slow at times, given everything that is happening with opioid abuse.

“Twenty years is a long time,” he says, “then I think of how long people have been trying to do this. No one has come up with anything better. We thought it might be worth a whole new approach.”