The ongoing opioid crisis in the U.S. has shortened life expectancy and caused untold suffering. The synthetic drug fentanyl has been particularly devastating, because it’s so potent compared to other opioids. New research in rats may offer a glimmer of hope, however: Scientists found that an experimental vaccine can prevent the behavioural and physiological effects of fentanyl, by producing antibodies that bind to the drug in the bloodstream. The work is detailed in a study published in late October in the journal Pharmaceutics.
This isn’t the first research to demonstrate a successful opioid-blocking vaccine in animals. And in fact, at least one oxycodone vaccine has made it to the initial stages of human clinical trials at Columbia University. But the October study adds support to this new approach to the opioid crisis — one that truly embraces the medical nature of addiction.
What is fentanyl and what’s the problem?
Fentanyl is a synthetic opioid, 50 to 100 times stronger than heroin. It was originally developed as a pharmaceutical and is now often used recreationally. Only a small amount is needed to produce a high (though not so small that first responders are at risk from merely touching it). Because of its potency, the drug is cheaper to source than others and has become a common adulterant in other drugs, like heroin, MDMA, and cocaine, either via intentional mixing or accidental contamination. Fentanyl use carries a high risk of overdose.
Opioid overdoses accounted for 75% of all drug overdose deaths in 2020, according to the CDC. More than 80% of those deaths involved a synthetic opioid like fentanyl. In almost every state, overdose deaths have been increasing, reaching their highest-ever numbers in 2020 and then again in 2021, when fentanyl killed more than 71,000 people. Opioid addiction is a health disaster in the U.S., and the prevalence of fentanyl is making it worse. Moreover, it’s a crisis that we’re currently ill-equipped to manage.
Fentanyl “use and overdose is a particular treatment challenge that is not adequately addressed with current medications,” wrote the the authors of the new study, who are primarily based in Houston, Texas. Current addiction treatments like methadone often require showing up at a clinic to take a dose every day. And most people, even with support, end up relapsing. Plus, naxolone, the treatment of choice for opioid overdose, often requires multiple doses to work and has been in short supply recently. A longer-lasting vaccine, on the other hand, could be a much more convenient and effective option.
How would a fentanyl vaccine work?
Similar to a flu shot, a fentanyl vaccine aims to work by prompting an immune system response. In the new study, researchers made their vaccine using a deactivated diphtheria protein already used in multiple FDA-approved shots, a molecule similar to fentanyl, a molecular bridge to link the two together, and a compound known to boost immune response in other vaccines The idea is to train the body to recognise fentanyl as a threat and create antibodies against the drug.
These antibodies bind with fentanyl in the bloodstream before the synthetic opioid can enter the brain. Then, instead of the drug triggering all its standard effects, it can be filtered out of the body and eliminated in an inert form by the kidneys (i.e., you just pee it out).
Past research suggests that some people’s immune systems make antibodies against opioids on their own, after repeat drug exposure. An effective vaccine could jumpstart that process.
How did the researchers test their vaccine?
To test their treatment, the scientists assessed whether or not the vaccine produced antibodies and reduced fentanyl brain levels in 60 rats. They also used smaller sample sizes of 32 and 28 rats for follow-up experiments testing the drug’s effects, post-vaccination.
Researchers ran a number of control and baseline tests on the rats, to assess their normal behaviour and physiology and to determine their responses while on fentanyl and an array of other opioids. In one of the tests, the scientists measured how quickly rats moved their tails away from a painful heat source. In another, they timed how long it took for trained rats to pull a lever for a food reward. They also collected physical data like heart rate and oxygen levels. Once the baseline was established, the researchers administered an initial vaccine dose to each rat, followed by two boosters at three-week intervals. Beginning six weeks from the initial dose, the study authors collected blood samples to check for fentanyl antibodies. And at 10 weeks, they started to re-test the rats behaviour and fentanyl response.
Across all of their tests, the researchers found that their vaccine worked. The rats produced the correct anti-fentanyl antibodies, their behavioural responses when given fentanyl became quicker after vaccination, their physiological responses to fentanyl lessened post-vax, and the levels of fentanyl in their brains were lower at the end of the experiment compared with a control. Plus, the researchers found the antibodies were specific to fentanyl and didn’t bind to other opioids like morphine, meaning vaccinated people could still receive pain medication if needed. They also noted some sex-specific findings, like that male rats seemed to produce more antibodies than females at certain time points in the study — which is important to note, as women are often underrepresented in drug trials. Finally, the researchers didn’t observe any negative side effects of vaccination in the rats.
What does it mean for people?
Often, experiments that yield successful outcomes in rodents don’t pan out in humans. Any approved vaccine resulting from this work would be, at minimum, years away. However, the research could be useful in developing future treatments and contributes to our understanding of opioids, addiction, and overdose.
“We believe these findings could have a significant impact on a very serious problem plaguing society,” said Colin Haile, an addiction researcher at the University of Houston’s Drug Discovery Institute in Texas and the lead study author, in a press release. And even though that significant impact won’t come immediately, it is a welcome glimmer of hope amid a dark and worsening trend.