A vaccine to block the effects of fentanyl, including overdose, is expected to enter human trials in the coming months, possibly leading to the first-ever active treatment for opioid use disorder.
Initial trials will focus on evaluating the safety of the vaccine, which was originally developed with funding from the U.S. Department of Defense. The shot was previously tested in rats and showed promising results. The product has now been licensed from startup ARMR Sciences, which plans to begin enrolling patients in a Phase I clinical trial in the Netherlands in January or February 2026.
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How do vaccines work?
The vaccine works by keeping fentanyl away from the brain, and this is done by targeting the fentanyl molecule with the immune system.
Fentanyl is a synthetic opioid that is 50 times more potent than heroin. Opioids, also called narcotics, act broadly by binding to opioid receptors in the brain and spinal cord, causing changes in nerve cell signaling that can prevent pain and produce a feeling of euphoria.
But because these opioid receptors are also found in the parts of the brain that control breathing, fentanyl, when used in excess, can also reduce breathing to levels that can be fatal. According to the Drug Enforcement Administration (DEA), 2 milligrams of fentanyl (the equivalent of about 12 grains of salt) can be deadly.
These effects can quickly be reversed if a person who has overdosed on fentanyl is treated with naloxone (better known by its brand name Narcan). This antidote also binds to opioid receptors, thus blocking the effects of fentanyl.
The ARMR vaccine takes a different approach, with the drug acting in the circulatory system before reaching the brain.
“This may be the first treatment that has no effect on symptoms.” [opioid] receptors,” Gage told Live Science.
What’s in the vaccine?
To prevent fentanyl from reaching the brain, the immune system must first recognize the drug. However, because fentanyl is a small molecule and not a pathogen like a virus, immune cells do not naturally react to its presence.
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To boost the immune response to fentanyl, ARMR co-founder and scientific advisor Colin Hale of the University of Houston and his colleagues had to link the opioid to something else.
They chose an inactivated diphtheria toxin called CRM197. This is a compound already used in vaccines on the market. When toxins are inactivated, they lose their toxicity and instead serve to evoke an immune response. To further boost this immune response, dmlLT, a compound distilled from a toxin produced by E. coli, was also added. The modified compound itself is not toxic and has been tested in humans in clinical trials for other unlicensed vaccines.
These two ingredients are attached to the synthetic portion of the fentanyl molecule, but by themselves they cannot cause euphoria or pain relief.
When the immune system encounters this fentanyl fragment, a combination of CRM197 and dmlT, it builds antibodies that react to real fentanyl. These antibodies bind to opioids and prevent them from crossing the brain’s protective membrane, the blood-brain barrier, and being removed from the body.
In a rat study, the vaccine stopped fentanyl from entering the rodents’ brains and also stopped the drug from suppressing breathing and causing overdose.
How are vaccines tested?
So far, research on this vaccine has been conducted in rodents, but dmLT and CRM197 have each undergone some testing and are already used in other vaccines in humans. Heil told Live Science that the rat protocol calls for an initial dose of fentanyl vaccine, followed by booster doses three and six weeks after the initial dose.
“The longest period of time that animals were followed in the study was about six months, and we found that the effects of fentanyl were completely blocked six months after the first vaccination,” Heil said. How this translates into “human years” remains to be seen, but researchers believe the vaccine will be effective for a long time in humans, as lab rats have a total lifespan of several years, he noted.
The first human trial, which will begin in early 2026, will enroll 40 people and will focus on detecting safety issues with the vaccine, such as unwanted or dangerous side effects. Researchers also plan to take blood samples from participants to see if the vaccine stimulates the production of anti-fentanyl antibodies.
If these Phase 1 trials are successful, the next step will be Phase 2 trials to test the vaccine’s efficacy, or how well it blocks the effects of fentanyl. In addition to tracking antibody levels over time, these trials also give some participants safe levels of fentanyl, which is used for pain relief in medical procedures. This is done under close supervision to ensure the vaccine works in the presence of the drug.
Are there any potential downsides to vaccines?
Fentanyl has legitimate medical uses as a painkiller, especially in emergency situations. One concern about vaccines is that vaccinated people will lose this option for pain relief.
However, Heil said the antibodies produced by vaccination do not bind to other opioids or other painkillers, such as morphine, oxycodone and methadone. That means there is an alternative if vaccinated people need pain relief in the future.
This drug also does not interfere with buprenorphine, which is used to treat opioid use disorder by reducing withdrawal symptoms and cravings. Haile said he and his team are currently testing the vaccine in combination with naltrexone, a non-opioid drug also used to block the effects of opioids in the treatment of drug use.
In theory, it might be possible to ingest enough fentanyl to override the body’s supply of anti-fentanyl antibodies, Heil said. But given that the vaccine blocks fentanyl’s euphoric effects, he expects people who want to quit will be less motivated to avoid it.
“We want people to come who want to quit drugs, who don’t want to use drugs,” he says. “Then they’ll have a chance to understand that this drug won’t get them high and there’s no point in taking it anymore.”
Who can benefit from the fentanyl vaccine?
Gage suggested one market for the vaccine could be first responders concerned about accidental fentanyl exposure. (That concern has grown in recent years as misinformation about fentanyl spreads.)
To be clear, if fentanyl gets on your skin through accidental exposure, for example, if you touch an object that has been exposed to the drug, fentanyl will not be absorbed through your skin. Significant absorption through the skin requires direct contact with the drug over several hours or days. However, if an EMT or police officer puts the drug on their hands and touches their mouth or eyes, they may feel some of the drug’s pain-relieving or pain-relieving effects, Heil said.
Gage said the vaccine could also be an “additional tool in the toolset” for people with opioid use disorder. He said the combination of vaccines, “intense” cognitive behavioral therapy, a type of talk therapy, and community support “could be incredibly beneficial for people who are just looking for another lifeline to recover.”
Finally, the vaccine could be beneficial for people who use less-lethal drugs such as cocaine, stimulants, and painkillers bought on the black market. That’s because fentanyl in these drugs is being cut more and more, and people can overdose without even knowing they’re taking opioids.
“I had two close childhood friends who died from fentanyl overdoses,” Gage said. “Neither of them were looking for it.”
Preliminary data estimates that more than 48,000 people will die of opioid overdose in the United States in 2024. Perhaps because of this high death toll, early studies suggest that people with personal experience with opioid use disorder and the general public alike are positive about the possibility of an anti-fentanyl vaccine. Only time will tell how well the new vaccine performs in human trials, but if it is ultimately approved, it could be the first to prevent overdose deaths.
This article is for informational purposes only and does not provide medical advice.
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