Some People Produce Antibodies to Opioid Drugs, Study Finds

Tablets believed to be laced with fentanyl are displayed at the Drug Enforcement Administration Northeast Regional Laboratory on October 8, 2019 in New York.
Tablets believed to be laced with fentanyl are displayed at the Drug Enforcement Administration Northeast Regional Laboratory on October 8, 2019 in New York.
Photo: Don Emmert (Getty Images)

Preliminary research out this week found that patients taking opioids for chronic pain can produce antibodies to the drugs, which could 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 disorder better than existing medications.


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

The findings were presented this week at the American Chemical Society Fall 2020 Virtual Meeting. That means the results are based on preliminary data that hasn’t yet gone through peer review. The sample size of 19 patients is also very small, so these conclusions are far from settled science.

But if true, the authors say, these antibodies could be part of the reason why 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 became painful. One theory that the researchers are exploring is that the metabolic byproducts that come from taking opioid drugs can bond to carbohydrates in the body, creating things called advanced glycation end products (AGEs). These AGEs have been linked to chronic inflammatory conditions such as diabetes and clogged arteries, which also involve the immune system.

“We think that the antibodies may be produced in response to the opioids modifying some proteins that are already normally part of the body. So while the antibodies can recognize opioids, in some cases they may also recognize elements of ‘self’, causing inflammation and further pain,” study author Cody Wenthur, a professor in the UW-Madison School of Pharmacy, said in an email. “We are very interested in following up on this concept through direct identification and structural determination of the modified proteins.”

The authors also speculate that these native immune responses may decrease the effectiveness of potential vaccines for opioid use disorder. Some scientists, including the authors of the study, 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 from these drugs when they enter the system, blocking them from getting into the brain and causing the effects associated with opioid abuse, such as an addictive euphoria. These vaccines, it’s theorized, would prevent craving symptoms better than other drugs now available, though they could be also used in conjunction with current medication-assisted therapy.

In the study, the volunteers produced IgM antibodies to opioids, which are short-term antibodies that usually last for a few weeks. But the vaccines these researchers and others are hoping to develop are trying to produce IgG antibodies, which typically last longer than IgM ones. The worry is that having this weaker native response will make it harder for the body to respond to the vaccine and produce a more effective antibody army.


Opioid vaccines aren’t universally seen as a good idea, with some harm reduction advocates arguing that the resources needed to develop them should be used to support other measures for helping people struggling with drug use, such as providing affordable housing and greater access to existing treatments. But if the authors are right, then even getting to the point where a vaccine for opioid abuse is effective will be harder than expected. Previous attempts to create vaccines for nicotine and cocaine dependence have also failed, though for different reasons.

Wenthur and his team don’t think these findings will sink the idea of an opioid vaccine, however. And by studying these antibodies more closely now, the researchers hope to better understand the effects of long-term opioid use as well as how to develop a successful vaccine moving forward.


“The possibility of generating an effective opioid vaccine is still very much alive. These results highlight a possible challenge and future opportunity; the concentration of anti-opioid antibodies in a person’s bloodstream prior to vaccination could help predict their relative sensitivity to vaccine efficacy and perhaps even help to inform the vaccine dose that they receive,” he said.

Wentur added that a research paper related to this work has been accepted by a peer-reviewed journal and should be published in a matter of weeks. They also plan to continue studying more people, including those with no history of opioid use, to validate their findings.


This article has been updated with comments from one of the study’s authors.

Science writer at Gizmodo and pug aficionado elsewhere



So if these things are modifying proteins, are they maybe creating those evil prions?  Plaques?  Alzheimer’s?