Taking Aim at Opioids

As the annual rate of overdose deaths from opioid painkillers rises, alongside deaths from other drugs, PBS researchers are finding solutions to the crisis in which so many communities find themselves.

Neuroscientists Andrea Hohmann, Ken Mackie and collaborators in their labs recently discovered a compound that, when administered with opioids used to treat chemotherapy-induced pain, prevents both tolerance and physical dependence on opioids in rodents. The drug could reduce the likelihood that chemotherapy patients become addicted to their pain management prescriptions. It also has the capacity to reduce pain in its own right, whether or not additional opiates are prescribed. And for those in treatment for overdose or addiction, this drug could lessen withdrawal symptoms.

The drug has yet another major advantage: It has already been proven safe for human consumption. Formerly tested in a clinical trial as a treatment for osteoarthritis knee pain, it was shown to be an ineffective treatment for this condition, yet nonetheless safe for people.

“The potential to quickly begin using this compound in combination with opioid-based medication to treat pain and reduce addiction makes this discovery very significant,” said Hohmann. “We already know this drug is safe for people, so moving into human trials will not require as many regulatory hurdles.”

To test the potential of the experimental drug to treat pain and reduce addiction symptoms, IU scientists administered the compound and the opioid morphine to male mice with chemotherapy-induced nerve pain. While morphine initially reduced the pain, the mice, like people, quickly developed tolerance to morphine’s effectiveness, requiring higher doses of opioids over time to achieve relief.

However, when a low dose of the experimental drug was combined with morphine, the mice no longer became tolerant to morphine. Even when they were no longer receiving the experimental drug, mice remained responsive to lower doses of opioids over time. They did not become tolerant. The researchers also found that higher doses of the experimental drug could produce sustained pain relief on its own without added morphine, when it was given at higher doses. Thus, the drug could prevent patients from building tolerance to opiate drugs or could replace the opiates altogether.

In another experiment, mice were given either morphine alone or in combination with the experimental drug. They were then treated with naloxone, which blocks the effect of opioids and induces opioid withdrawal symptoms. Remarkably, Hohmann said, the experimental drug also decreased the severity of the withdrawal symptoms, which suggests that the drug could be used as a means to wean individuals off opioids.

The study appeared in the journal Molecular Pharmacology. Its first author is Xiaoyan Lin, a postdoctoral research associate in the Hohmann Lab. Additional authors are Amey S. Dhopeshwarkar, an assistant scientist; and Megan Huibregtse, an undergraduate at the time of the study.