Unraveling the Genetic Mystery of Opioid Addiction

Twenty years ago, U.S. doctors began to treat pain more aggressively. Millions of Americans were so debilitated by chronic pain that they couldn’t eat, sleep or work and their doctors thought opioid painkillers would be a godsend. For the majority of pain sufferers, they were. But for the rest, the drugs became a nightmare.

“There were 100 million people suffering from chronic pain,” says Janet Robishaw, Ph.D., chair of the Charles E. Schmidt College of Medicine Department of Biomedical Sciences. But the opioid solution came with an undesirable side effect. “Opioids activated the reward pathway (in some people) as well as treating their pain. This made them want to use it again.”

The result has been an American tragedy — the tale of ordinary Americans who sought legal prescription pain relief but were sabotaged by their own bodies. They are likely to have genetic variations that make them targets for opioid use disorder — commonly referred to as addiction, says Robishaw. Many of these Americans make headlines when their addiction drives them to ever more powerful street opioids and they end up as overdose victims.

“Four out of five people can be put on opioids,” says Robishaw. “But one in five will develop opioid use disorder. At this time, we don’t know how to identify them in advance.”

The genes involved in this process are still unidentified, Robishaw says. But that could change. With a $4 million grant from the National Institutes of Health, Robishaw is working with a large patient cohort who are being treated for chronic pain with opioid medications. As it becomes clear who is addicted, she and her team can compare their genes with those of unaddicted subjects and hunt for genetic variations.

Eventually that knowledge could lead to genetic testing that would enable doctors to determine which patients had drawn the short straw. Doctors could then focus on alternative treatments for their pain. The research could also lead to drugs that could shut down the reward-producing pathways that make the drugs addictive.

“We want to be able to appropriately prescribe opioids to those who will receive the most benefit,” she says. “And we want to be able to avoid those who have genetic risk factors and show most risk for opioid use disorder.” But Robishaw cautions it will take considerable time to identify the genetic variants.

In the meantime, the death toll continues to rise. In Palm Beach County, opioid deaths occurred on average every 15 hours, a recent Palm Beach Post analysis found. For the full year, opioids killed 590 people, almost twice the toll of the year before. The majority of those had fentanyl in their system. Fentanyl is an opioid 100 times stronger than morphine. The newspaper’s inquiry also found that 109 had died from carfentanil, an opioid-based elephant tranquilizer 10,000 times stronger than morphine.

The research done by Robishaw’s team might someday provide a way to help avoid these losses. “This will be expensive and time consuming,” says Robishaw. “But (considering the alternative), it will be worth it.”