Antibodies to opioids discovered in long-term users

Novel research, recently presented at the American Chemical Society Fall 2020 virtual meeting, has described the discovery of opioid antibodies produced by the immune system following chronic opioid use. The researchers suggest these antibodies may be responsible for some negative side effects seen in long-term opioid users.

“Opioid use disorder and opioid overdoses continue to be a major epidemic in this country,” says Cody Wenthur, from the University of Wisconsin–Madison. “A relatively new therapeutic approach entering clinical trials is what in shorthand we call an opioid vaccine, where the immune system generates a response against the drugs. But for this approach to be successful, we need to identify the people who would benefit from that approach.”

The first challenge the researchers faced was homing in on exactly what opioid-related molecules could trigger production of immune antibodies. Common opioids such as hydrocodone or oxycodone are too small for the immune system to recognize, so the researchers needed to look at downstream effects when these molecules enter the bloodstream.

Some molecules don’t trigger immune responses until they combine with larger carrier proteins in a process called haptenization. It is these opioid-protein conjugates the new research focused on.

The study developed a new technique to detect any immune antibodies produced in response to opioid molecules. The technique was then tested in a small cohort of 19 subjects who had taken prescription opioids for chronic back pain. In 10 of those subjects the researchers discovered anti-opioid antibodies. A clear correlation was also seen between higher doses and larger antibody responses.

"This was surprising," says Jillian Kyzer, another researchers working on the project. "We saw antibody responses in people who were taking large doses for as little as six months."

The research is not yet published in a peer-reviewed journal and much more work is needed to verify these results in larger cohorts, but the researchers do suggest this antibody discovery could help explain why long-term opioid users develop negative side effects over time.

Hyperalgesia, for example, is one of those unexplained long-term side effects occasionally seen in chronic opioid use. The condition, essentially an extremely painful sensitivity to general touch, is not well understood and the new study hypothesizes this antibody immune response relating to opioid use may be part of its cause.

Another compelling outcome from the antibody discovery is a way to better understand the efficacy of a number of opioid vaccines currently in development. For several years researchers have been working to create a vaccine that can stop the high people seek from opioids. The new research suggests subjects with high pre-existing opioid antibody loads may not respond well to prospective opioid vaccines.

"The research could also be helpful in identifying efficacy biomarkers for opioid vaccines that are entering clinical trials," says Kyzer. "If our findings hold up in subsequent research, you would expect individuals with higher levels of these antibodies to be poor candidates for anti-opioid vaccine therapy."

The video below gives a brief overview of the research.

Sources: University of Wisconsin–Madison, American Chemical Society