In a new study, researchers have discovered that a majority of back-pain patients they tested who were taking opioid painkillers produced anti-opioid antibodies.
These antibodies may contribute to some of the negative side effects of long-term opioid use.
Existing antibodies may also limit the benefit a patient receives from an anti-opioid vaccine, the production of which is the ultimate goal of this line of work.
A vaccine stimulating an immune response against opioids could reduce the harm of opioid abuse, but researchers must identify the population of patients that will respond well to that treatment.
The research was conducted by a team at the University of Wisconsin-Madison and elsewhere.
In the study, the team discovered antibodies against protein-bound opioids in 10 of 19 patients who took opioids to treat chronic lower back pain.
Those who took higher doses of opioids had a stronger antibody response. A control group of three patients who did not take opioids for their back pain had only very low levels of anti-opioid antibodies.
For this initial study, the team could only identify three patients with chronic pain who had not previously taken opioids, even after a months-long radio and print recruiting campaign.
This challenge was an indication of the ubiquity of these drugs, despite evidence that they are riskier options than non-opioid painkillers for treating chronic pain.
The team says opioid use disorder and opioid overdoses continue to be a major epidemic in this country.
A relatively new treatment is an opioid vaccine, where the immune system generates a response against the drugs.
But for this approach to be successful, doctors need to identify the people who would benefit from that approach.
For decades, researchers have understood that the immune system can produce antibodies against psychoactive drugs under the right conditions.
While the chemicals themselves are too small for the immune system to recognize, they can permanently bind to large proteins in the blood, which can then trigger an immune response.
If a vaccine can produce antibodies capable of neutralizing the drugs, it could help people combat addiction by reducing the pleasurable feelings the drugs produce in the brain.
Past trials of vaccines against nicotine or cocaine have had limited success, in part because of individual differences in how the immune system produces antibodies.
To test that idea, the team looked for antibodies against the drugs in people who took opioids.
They linked the common opioid hydrocodone and oxycodone to a ubiquitous blood protein in the hopes that these drug-protein conjugates would bind to any opioid antibodies in patients’ blood.
Counterintuitively, the patients who already produce a measurable antibody response to opioids may be the least likely to benefit from a potential anti-opioid vaccine.
That’s because they produce a relatively weak type of antibody, known as IgM, which may reduce their ability to generate stronger, neutralizing IgG antibodies against the same drug target in the future.
As researchers advance toward a potential opioid vaccine, tests like this one might help identify the patients who are likely to benefit.
One author of the study is Cody Wenthur, a professor in the UW-Madison School of Pharmacy.
The study was presented at the American Chemical Society Fall 2020 virtual meeting.
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