Some people make antibodies to opioids, study finds

Preliminary research this week found that patients taking opioids for chronic pain may produce antibodies to the drugs, which may help explain some of the side effects of long-term opioid use; these antibodies may also hamper efforts to create opioid vaccines, which scientists hope could treat opioid use disorders better than existing drugs.

Researchers at the University of Wisconsin-Madison and the Scripps Research Institute in California took blood samples from 19 volunteers who were taking opioid pain relievers for chronic low back pain. They then screened these samples for antibodies to opioids, exposing the blood to proteins bound to commonly used opioids, hydrocodone and oxycodone. In 10 of these patients, they found antibodies specific to opioids. Those with a higher dose of opioid therapy had higher levels of these antibodies, while three control patients who were not taking opioids for their pain had none at very low levels.

The results were present this week at the American Chemical Society’s Fall 2020 Virtual Meeting. This means that the results are based on preliminary data that has not yet been peer reviewed. The sample size of 19 patients is also very small, so these findings are far from an established science.

But if this is true, say the authors, these antibodies could be part of the reason that people who take opioids can develop symptoms such as hyperalgesia, where a person’s sensitivity to pain becomes so extreme that even normally harmless sensations become painful. One theory that researchers are exploring is that the opioids in these drugs can bind to carbohydrates in the body, creating things called advanced glycation end products (AGEs). These EGMs have been linked to chronic inflammatory conditions like diabetes and blocked arteries, which also involve the immune system.

The authors also believe that these native immune responses may decrease the effectiveness of potential vaccines for opioid use disorders. Some scientists, including the study’s authors, are hoping to create vaccines that can induce a temporary antibody response to the opioids we get from a prescription pill or illicit drug. The antibodies would cling to the molecules of these drugs when they entered the system, preventing them from entering the brain and causing the effects associated with opioid abuse, such as addictive euphoria. These vaccines, it is theorized, would prevent urgent need symptoms better than other currently available drugs, although they can also be used in conjunction with current drug therapy.

In the study, volunteers produced IgM antibodies against opioids, which are short-term antibodies that usually last a few weeks. But the vaccines these researchers and others hope to develop attempt to produce IgG antibodies, which typically last longer than IgM antibodies. The concern is that this weaker native response will make it more difficult for the body to respond to the vaccine and to produce a more efficient army of antibodies.

Opioid vaccines are not universally seen As a good idea, some harm reduction advocates arguing that the resources needed to develop them should be used to support other measures to help people struggling with drug use, such as providing affordable housing and better access to existing treatments. But if the authors are correct, even getting to the point where an opioid abuse vaccine is effective will be more difficult than expected. Previous attempts to create nicotine and cocaine addiction vaccines have also failed, although for different reasons.

“In order to confirm these results and to help us understand who might be good vaccine candidates, we need to find a larger cohort of individuals, track their history of opioid use and determine if they are a useful biomarker for subsequent vaccine protection against overdose and for clinical outcomes like hyperalgesia, ”study author Cody Wenthur, professor at the UW-Madison School of Pharmacy, said in a statement released by the university.

By studying these antibodies now, researchers hope to gain a better understanding of how to develop their vaccines in the future.