Opioid Alternative Could Come from Old Osteoarthritis Drug Candidate

A drug previously studied for its potential in treating osteoarthritis pain could find new life as an alternative to opioid-based painkillers, according to researchers from Indiana University. The study – the results of which were published in the journal Molecular Pharmacology – suggests that the drug could block neuropathic pain signals while decreasing opioid dependence.

Originally developed by Eli Lilly, the CB₂ cannabinoid agonist did not meet efficacy endpoints in clinical trials of osteoarthritis pain. But according to the researchers involved in the current study, since the drug was previously shown to be safe in human patients, it could benefit from a faster pathway to approval if it shows promise in treating other types of neuropathic pain.

“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 lead investigator Dr. Andrea G. Hohmann, a Linda and Jack Gill Chair of Neuroscience and professor in the IU Bloomington College of Arts and Sciences’ Department of Psychological and Brain Sciences. “We already know this drug is safe for use in people, so moving into human trials will not require as many regulatory hurdles.”

Like other academic centers, Indiana University has recently launched a program to address the growing opioid epidemic, a crisis that claimed the lives of 64,000 Americans in 2016. The Responding to the Addictions Crisis Grand Challenge is a $50 million program aimed at preventing and reducing the incidence of opioid addictions in the state.

The researchers tested the CB₂ cannabinoid agonist along with morphine in male mice models of neuropathic pain. Much like the human response to the opioid, the research team found that the mice built up a tolerance to morphine’s painkiller effects over time, requiring them to be injected with higher doses of the drug in order to achieve the same level of pain relief.

But the addition of the CB₂ cannabinoid agonist prevented the development of opioid tolerance in the mice which was sustained even after the researchers stopped administering the experimental drug. On its own, the CB₂ cannabinoid agonist was also able to produce pain relief, suggesting it could be a viable alternative to highly-addictive opioid drugs like morphine.

Further experiments showed that the drug could help reduce opioid withdrawal symptoms when administered with the opioid overdose treatment naloxone. Reducing the severity of opioid withdrawal symptoms could help individuals make it through the detox process and help prevent relapse.