Some People’s Immune Systems Produce Antibodies To Opioids, New Research Suggests

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One of the many things that can make it so difficult to kick opioids is the chronic inflammation and heightened pain sensitivity that can develop after long-term use. According to new research, these side-effects might occur because the body produces antibodies against the drugs.

Scientists at the University of Wisconsin-Madison School of Pharmacy, Scripps Research, and Scripps Clinic took blood samples from 19 patients who used opioids, either hydrocodone or oxycodone (sold under the brand name OxyContin), for chronic back pain and three control patients who used over-the-counter remedies.

They discovered that specific anti-opioid antibodies were in the blood plasma of 10 people who regularly took prescription opioids, but almost none were found in those who used non-prescribed painkillers and therapies. By no coincidence, the antibody response was larger in people who were taking larger doses. However, the team also found that taking opioids can have this effect on the immune system within just a matter of months. 

Since the body is mounting an immune response to the drugs, much like how it would to a pathogen, this could explain some of the unpleasant side-effects of long-term opioid abuse and opioid use disorder, say the researchers.

"This was surprising," Dr Jillian Kyzer from the University of Wisconsin-Madison said in a statement. "We saw antibody responses in people who were taking large doses for as little as 6 months."

The researchers presented their research at the American Chemical Society (ACS) Fall 2020 Virtual Meeting & Expo on Monday, August 17.

Scientists have known for decades that some psychoactive drugs can spark the immune system to produce antibodies, however, it was assumed that hydrocodone or oxycodone was not large enough to get the attention of the immune system. In the new research, the researchers argue the opioid can create a larger molecule in a process called haptenization, in which big proteins latch onto the drug molecules, and thereby allow the immune system to recognize it as an antigen.

Although the study was on the small side — a mere 19 patients were tested in the study — the researchers say their findings could have some big implications for the development of an anti-opioid vaccine. In a bid to tackle North America’s opioid epidemic, scientists have attempted to develop a vaccine that helps to produce antibodies capable of neutralizing the drugs. This could help reduce the pleasurable sensations of the opioid and aid people in dealing with addiction. 

This recent discovery of opioids producing antibodies actually came about through the team’s work on developing an anti-opioid vaccine. Off the back of their discovery, they believe the antibodies could be used as a biomarker to help identify the people who are likely to benefit from such a vaccine. However, as always, further research is needed.

“In order to confirm these results and help us understand who might be good vaccine candidates, we need to find a larger cohort of individuals, track their opiate use history, and figure out if this is a useful biomarker for subsequent vaccine protection against overdose and for clinical outcomes like hyperalgesia,” lead researcher Cody Wenthur, a professor in the UW–Madison School of Pharmacy, said in another statement.

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