A vaccine that blocks fentanyl from entering the brains of rats – thereby stopping the addictive high – could one day be used to fight the opioid crisis.
Importantly, the vaccine did not block the action of other, non-fentanyl opioids, suggesting that it may not prevent pain relief in humans by other means.
“We believe these findings could have a significant impact on a very serious problem that has plagued society for years – opioid abuse,” says University of Houston neuroscientist Colin Hale, the study’s lead author.
In the study, researchers gave rats three doses of the fentanyl vaccine three weeks apart. Another group of rats received a placebo.
The researchers took blood samples at regular intervals, showing an accumulation of anti-fentanyl antibody levels over time in the vaccinated rats.
After completion of the vaccination schedule, the rats were given a dose of fentanyl.
To measure whether the vaccine blocked the pain-relieving effect of fentanyl, the researchers tested the pain responses of the immunized rats by heating the rats’ tails for no more than 10 seconds and seeing how long it took them to withdraw.
In another experiment, they exposed rats to a fire pit and measured how long it took them to lick their rear ends.
The vaccinated rats moved away from the painful stimuli faster than the control group in both experiments, showing that the vaccine – when given in higher than two doses – blocked the pain-relieving effect of fentanyl.
A post-mortem examination revealed that the vaccine had reduced the amount of fentanyl in the brain.
“Our vaccine is able to produce anti-fentanyl antibodies that bind to ingested fentanyl and prevent it from entering the brain, allowing it to be eliminated from the body through the kidneys,” says Haile.
Researchers they didn’t notice any unwanted side effects in the immunized rats that participated in the lab studies, but of course more work is needed to move the vaccine into clinical trials.
Researchers are now preparing for human trials.
They expected to see few side effects because the fentanyl vaccine consisted mostly of ingredients already approved for use in human vaccines: a small fentanyl-like molecule attached to a larger carrier protein called CRM197, which is approved for use in human vaccines, and an adjuvant molecule called dmLT that adds an extra immune boost and has been shown to be safe in many clinical trials.
Together, these ingredients stimulate the immune system to recognize fentanyl as a threat and produce antibodies that prevent the chemical from reaching the brain, similar to how a flu shot trains the immune system to recognize a specific target.
The synthetic opioid fentanyl is about 100 times more powerful than morphine. Doctors have been widely prescribing it for severe pain since the 1990s, leading to an “opioid epidemic” in the United States, where more than 150 people die of fentanyl overdoses every day.
It only takes about 2 milligrams of fentanyl to kill a person. Illegal drugs such as heroin are often mixed with fentanyl to give them an extra kick – a problem that has led police to issue warnings about deadly illegal drugs circulating on the black market.
Studies show that up to 90 percent of people who seek treatment for opioid use disorder will relapse due to addiction.
Naloxone can be used in an emergency to prevent a fatal fentanyl overdose, and everyday medications like methadone can reduce cravings and withdrawal, prevent overdose deaths, and help people stay off fentanyl – but it all depends on the people who follow the treatment.
However, a vaccine that works over a longer period of time to block fentanyl’s effect could help people overcome addictions more quickly, potentially reducing fentanyl deaths.
The study was published in Pharmaceutical.