by American Chemical Society

larger the dose of opioid, the larger the antibody response. “This was surprising,” Kyzer says. “We saw antibody responses in people who were taking large doses for as little as 6 months.”

The scientists are now working on isolating the key opioid antigenic intermediates in the body that prompt the generation of antibodies. One possibility is that the intermediates are modified proteins known as advanced glycation end products (AGEs), which could form when hydrocodone or oxycodone metabolites react with a carbohydrate. AGEs have been implicated in diseases such as atherosclerosis, cancer and Alzheimer’s disease, and they might help explain chronic inflammation in long-term opioid users. The researchers have observed preliminary signals of hydrocodone-associated AGE formation under conditions relevant to those found in the human body, and they are planning to validate these results soon.

Wenthur says the findings support undertaking a broader study to determine the prevalence of antibodies in people based on race, age and sex. “The research could also be helpful in identifying efficacy biomarkers for opioid vaccines that are entering clinical trials,” Kyzer says. “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.”

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Patients taking long-term opioids produce antibodies against the drugs
More information: Investigation of the mechanism of immunologic response to chronic opioid use:
Abstract
Long-term opioid use has not been shown to be more effective than NSAIDS for chronic pain, however one study showed that 61% of patients with chronic back pain were prescribed opioids at least once in the previous year, and 31% of patients were categorized as long-term opiate users. In addition to the risk of developing opioid use disorder (OUD), long-term opioid use has been shown to cause chronic inflammation and hyperalgesia, suggesting that opioids may induce an immune response upon chronic use.
To investigate this hypothesis, plasma samples were obtained from individuals with chronic back pian who had been prescribed opioids as well as negative controls. The plasma samples were analyzed by enzyme-linked immunosorbent assay (ELISA), screening against bovine serum albumin (BSA) conjugated to either oxycodone or hydrocodone to quantify the levels of opioid-specific antibodies in the samples Varying levels of antibodies were found, and we thus investigated the potential mechanism by which these antibodies were produced. As other drugs containing secondary amines have been shown to form advanced glycation endproducts (AGEs) which can generate self-reactive antibodies, we hypothesized that norhydrocodone and noroxycodone would as well. We investigated the potential for norhydrocodone to form AGEs through monitoring in vitro formation of reactive intermediates.

Provided by American Chemical Society