Freeman tackling risks of opioid use

Opioid misuse has become a public health crisis. According to the U.S. Department of Health and Human Services (HHS), more than two million Americans live with an opioid use disorder, and overdose deaths have quadrupled since 2002.
A problem of this magnitude will require a multi-faceted effort, including one Jackson scientist who is developing new approaches to curb the risks associated with opioid use.
Dr. Kevin Freeman, an associate professor in the Department of Psychiatry and Human Behavior at the University of Mississippi Medical Center, spoke at the Rotary Club of North Jackson recently about the causes and countermeasures for the opioid crisis, including his own research.
Freeman said converging factors in the 1990s led to the current opioid crisis. First, physician and hospital groups started to consider pain as a vital sign, a condition that must be managed. Next, pharmaceutical companies made claims that prescription opioids were non-addictive, based on limited evidence.
When providers and researchers realized the medication’s high-abuse potential, they tightened prescription access and monitored use more closely. This resulted in what Freeman calls a “pharmaceutical industry-driven, prescription-supported” situation where people who had developed opioid use disorders have difficulty getting prescriptions for oxycodone or other opioids.
“A huge problem with prescription opioid abuse is that people who become dependent exhaust their doctor-shopping options, and then they start buying them on the streets where an oxycodone pill could cost $30,” he said. “If they’re unable to afford it, they may transition to heroin because it’s a much cheaper alternative, and the illicit market has capitalized on this increased demand with greater availability of heroin.”
According to HHS data, overdose deaths associated with prescription opioids leveled off around 2010, while heroin overdose rates grew exponentially. The same trend occurred with synthetic opioids such as fentanyl, which are much more potent.

Systemic countermeasures at the state and national level include prescription drug monitoring and medication assisted therapies, such as methadone and buprenorphine. At UMMC, Freeman is studying ways to innovate the opioid medications themselves.
Through the aid of a five-year, $2 million grant from the National Institutes of Health, Freeman’s lab is testing ways to create abuse-deterrent formulations of prescription opioids.
Their primary project involves compounding oxycodone with nalfurafine. This anti-itch medication approved for sale in Japan can cause nausea and other negative side effects, which could deter people from using the drug in higher doses than prescribed. Finding the right balance of the two compounds is a Goldilocks scenario.
“Too heavy-handed an approach can have negative consequences,” Freeman said. If the side effects are too severe, people may not take the medication and their pain will persist. “So, we’re trying to add enough so that the patients only experience the negative effects when the medication is taken more frequently or at higher doses than prescribed.”
His most recent results suggest that the drug combination is more resistant to overuse. Furthermore, nalfurafine is also a mild analgesic. This means that adding it to oxycodone can increase the pain-killing power of the formulation. It’s possible that one day people may be able to use abuse-deterrent formulations like this that contain lower doses of oxycodone or other prescription opioids.
The lab is also beginning to study other compounds that can be added to opioid medications to reduce the risk of addiction. Freeman’s lab is also collaborating with the University of Mississippi’s National Center for Natural Products Research on a separate NIH-funded project studying an opioid-cannabinoid compound.
“The long-term goal of these research projects is to provide physicians with a new opioid pain medication that can be used to treat pain without having the risk of abuse liability in their patients,” Freeman said.


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