Could this experimental synthetic opioid break the cycle of addiction? | McClatchy Washington Bureau

Prescription opioids help millions of Americans deal with pain, but their addictive qualities have themselves created a public health problem: rising rates of opioid dependence, addiction and overdose.

To help curb the nation’s appetite for the powerful painkillers, including OxyContin, morphine and Percocet, researchers at the University of Maryland, Baltimore, are developing a synthetic opioid that they say stops pain without causing physical dependence.

“We’ve filed a patent and we’ve been told that it’s about to come out in a couple of weeks,” said Andrew Coop, a professor at the University of Maryland School of Pharmacy who’s leading the research.

While a patent for a new molecular entity would be a huge step, Coop said the new compound, dubbed “UMB425,” is still many years and many hurdles from being available to patients. But early tests on mice have been successful.

“We designed this so that when you discontinue the drug, the patient doesn’t go into withdrawal symptoms,” said Coop, who’s also the associate dean of academic affairs. “We have shown that it doesn’t cause dependency. At the moment, we’ve shown this just in animals. The aim is to move this into clinical” tests on humans.

The experimental compound is the result of more than 10 years of research by Coop, and the drug’s co-inventor, Alex MacKerell, director of UM’s Computer-Aided Drug Design Center.

If UMB425 one day passes muster with the U.S. Food and Drug Administration, it could one day help make pain management much safer by reducing the likelihood of addiction.

“That would be a phenomenal drug to have,“ said Jon Essenburg, regional administrator with Operation PAR, a non-profit that operates the only methadone clinic in Manatee County, Florida. “If it does basically everything that a regular opioid does without causing the physical dependence, then that's definitely an improvement.”

Both Essenberg and Mark Sylvester, an addiction psychologist in the Bradenton, Florida, area, expressed skepticism about the drug, but applauded the effort.

“It’s an exciting area of research and I think there’s many more discoveries to be made,” Sylvester said. “But it might be a little bit premature to say it’s a potential solution to the problem.”

Other weren’t so diplomatic.

“I’ve never heard of a non-addictive opioid, and I’ll believe it when I see it,” said Dr. Caleb Alexander, Co-Director of Center for Drug Safety and Effectiveness at Johns Hopkins University in Baltimore.

While there’s a need and opportunity to bring safer, more effective opioids to market, Alexander said the FDA should also provide much greater scrutiny of new products.

“Now that we know just how deadly these products are, I think there’s a higher bar to (FDA approval) than there has been historically. And for good reason,” Alexander said….“For far too long we have overestimated the effectiveness of these drugs and underestimated their risks….They have been vastly overused at great detriment to the public health.”

A class of narcotic pain medications, opioids include not only prescription drugs, but also the illegal drug heroin.

Nearly two million Americans either abused prescription opioids or were dependent on them in 2014, according to federal estimates. And up to 25 percent who take prescription opioids over several months for non-cancerous pain will struggle with addiction and physical dependence.

Dr. Michael Carome, Director of Public Citizen’s Health Research Group, said that without any testing in humans, it’s just too early for optimism about UMB425 since most drugs that show promise in the animal-testing phase don’t ever make it to market.

“The promise that such a drug would have, obviously, would be great,” Carome said. “But I think we have to be skeptical that they have found the magic bullet for treating pain.”

In an e-mail, Coop said there have been many “false dawns” where drug testing success in animals hasn’t measured up in humans.

“However, there is very strong evidence for (UMB425), and past failures should not stop our search for improved pain medications.” he wrote. “Pain causes unbelievable suffering in many, many patients and we owe it to all patients to continue to push the boundaries of knowledge to reduce their suffering.”

While some prescription opioids are more addictive than others, they can all cause dependence and addiction if taken without proper supervision.

Opioids reduce the perception of pain by attaching to proteins in the brain called opioid receptors. Of the three main types of opioid receptors - mu, delta and kappa – opioids work mainly through the mu receptors to relieve pain.

For reasons that scientists have not fully explained, blocking the delta receptors stops the development of opioid dependence and the onset of withdrawal symptoms, Coop said.

UMB425 is designed to activate the mu receptors to relieve pain and simultaneously block the delta receptors, which reduces cravings for the pain-killing drug once it’s discontinued.

The drug’s unique ability to act on both receptors is the basis for the patent application, Coop said.

One potential problem, however, is that UMB425 might provide a euphoric high, which presents an opportunity for illicit usage, Coop said. “We don’t have evidence either way, but it probably would,” make users high, Coop added.

To reduce the chance for abuse, Coop said he could change the formulation of the drug, possibly by adding other ingredients or changing the way it’s administered.

While users could potentially become addicted to the drug’s euphoric high, Essenberg said “it would end up being way easier to treat the addiction without having the physical withdrawal that goes along with it. So in that regard, this would be something terrific.”

Grants from the National Institutes of Health have funded most of Coop’s research, but he’s also seeking state funding to spin off a start-up company through the university. The new company would try to secure federal small business funding designed specifically for drug development, Coop said.

The money would help fund additional safety testing for the drug, which is necessary before it can be administered and tested in humans.

Coop also wants to develop a second and third candidate drug that works the same way as UMB425, but has a different molecular structure. Doing so improves the chances for possible FDA approval, he said.

Other researchers around the country are also working to develop a less-addictive prescription opioid. None of the efforts have reached the clinical testing phase.

Coop said the friendly competition ensures that each research team applies the best science.

“Because at the end of the day, it’s about getting the compound out there for the patients,” Coop said.