Prescription opioids, medication, antibiotics with many bottles of pills in the background. Concepts of addiction, opioid crisis, overdose and doctor shopping

(© Kimberly Boyles -

MADISON, Wis. — Although opioids can be highly effective at reducing pain, long-term use can lead to addiction, disorders, and negative side-effects like increased sensitivity to pain or chronic inflammation. According to a new study by the University of Wisconsin-Madison, anti-opioid antibodies in a user’s own immune system may actually trigger certain side effects.

“Extrapolating from previous work on opioid vaccines, we started thinking that the patient’s own immune system could be responsible for some of the negative effects of long-term opioid use,” says lead researcher Cody Wenthur in a media release. “We thought the body could be mounting an immune response and making antibodies against the drugs.”

The body defends against opioids

Common prescription opioids include OxyContin, Vicodin, and fentanyl. Illegal opioids include narcotics like heroin. Although the scientists began to think that there may be some link between opioid issues and the immune system, there is one problem with that hypothesis. Common pain killers contain small molecules that the immune system is unlikely to recognize. If opioids bind to larger molecules like proteins in the bloodstream however, they can then trigger an immune response.

To test their theory, scientists collected blood samples from 19 patients who used hydrocodone or oxycodone for chronic back pain. For comparison, the study also collects blood from three patients who use non-opioid over-the-counter medications.

To detect anti-opioid antibodies, the Wisconsin team had to develop a new technique which links the two medications to a common blood protein. They then add in the patient’s blood. If the blood sample contains antibodies for hydrocodone or oxycodone, it triggers a chemical reaction that produces a colorful dye. In this way, the scientists can see whether or not anti-opioid antibodies are present depending on the color.

Using this technique, the study finds over half of the opioid users’ blood samples contain anti-opioid antibodies. Researchers add that the longer patients use opioids, the greater the immune response is. In contrast, the report does not find any anti-opioid antibodies among patients using over-the-counter pain medications.

“This was surprising,” postdoctoral researcher Jillian Kyzer says. “We saw antibody responses in people who were taking large doses for as little as 6 months.”

Who should be getting these prescriptions?

The researchers caution that more studies are needed to better characterize the prevalence of antibodies across different races, ages, and genders. They add that the findings could one day help physicians figure out who should and should not be on opioids.

“The research could also be helpful in identifying efficacy biomarkers for opioid vaccines that are entering clinical trials,” Kyzer explains. “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 Wisconsin researchers are presenting their study at the American Chemical Society Fall 2020 virtual meeting.

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