A vaccine that blocks fentanyl from entering the brain in rats – thus stopping the addictive high – could one day be used to combat the opioid crisis. Importantly, the vaccine did not block the action of other, non-fentanyl opioids, suggesting that it may not prevent pain relief for humans via other means. "We believe these findings could have a significant impact on a very serious problem plaguing society for years – opioid misuse," says University of Houston neuroscientist Colin Haile, the lead author of the study. In the study, researchers gave rats three doses of the fentanyl vaccine at three-week intervals. Another group of rats received a placebo. Researchers took blood samples at regular intervals, showing a build-up of anti-fentanyl antibody levels over time in the vaccinated rats. After the vaccination schedule was complete, the rats were given a dose of fentanyl. To measure whether the vaccine was blocking the painkiller effect of fentanyl, the researchers tested the immunized rats' pain responses by heating up the rats' tails for no more than 10 seconds and seeing how long they took to pull away. In another experiment, they exposed the rats to a hotplate and timed how long it took them to lick their hind limbs. The vaccinated rats pulled away from painful stimuli faster than the control group in both experiments, showing that the vaccine – when administered at the higher of two doses – was blocking the painkiller effect of fentanyl. A post-mortem examination revealed that the vaccine had lowered the amount of fentanyl in the brain. "Our vaccine is able to generate anti-fentanyl antibodies that bind to the consumed fentanyl and prevent it from entering the brain, allowing it to be eliminated out of the body via the kidneys," says Haile. Researchers didn't observe any adverse side effects in the immunized rats involved in lab studies, but of course, more work is needed to move the vaccine to clinical trials. The researchers are now preparing for trials on humans. They expect to see few side effects because the fentanyl vaccine was mostly made up of components that have already been approved for use in human vaccines: a small fentanyl-like molecule attached to a larger carrier protein called CRM197, which has been approved for use in human vaccines, and an adjuvant molecule called dmLT that adds an extra immune boost and has been proven safe in many clinical trials. Together, these components stimulate the immune system to recognize fentanyl as a threat and produce antibodies that prevent this 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 around 100 times more potent than morphine. Doctors have widely prescribed it for severe pain since the 1990s, leading to an 'opioid epidemic' in the United States, where more than 150 people die from fentanyl overdoses every day. It only takes around 2 milligrams of fentanyl to kill a person. Illicit drugs like heroin are often mixed with fentanyl to give them an extra kick – a problem that has led police to issue warnings about deadly illicit drugs circulating on the black market. Studies suggest that as many as 90 percent of people who seek treatment for opioid use disorder will relapse due to the addictiveness. Naloxone can be used in an emergency to prevent a fatal fentanyl overdose, and daily medications like methadone can reduce cravings and withdrawal, prevent overdose deaths, and help people stay off fentanyl – but all that depends on people adhering to treatment. However, a vaccine that works over a longer timeframe to block the effect of fentanyl could help people overcome addictions faster, potentially reducing fentanyl fatalities. Source
