Drug-overdose deaths now exceed the number of people dying in car crashes in the U.S. They dwarf deaths from gunshots. And for opioids—which led to some 33,000 deaths in 2015—the numbers are continuing to rise. Preliminary data for 2016 suggests there were more than 50,000 opioid overdose deaths.

The surge is renewing public focus on efforts to develop vaccines that would block the drugs’ euphoric effects and therapies that would tamp down the extreme withdrawal symptoms that can leave an addict feeling like they will die unless they get a fix. “One of the exciting things that [scientists are] actually working on is a vaccine for addiction,” Tom Price, Health and Human Services secretary said in a press conference last week. Opioid vaccine work is “incredibly exciting,” he added. But not everyone is so sanguine.

To better understand if the White House’s enthusiasm is warranted, Scientific American interviewed the lead investigators of the top three opioid vaccine candidates—and came away with some sobering news: None of those candidate vaccines have made it to human trials, which suggests it may be many years before they reach patients—if at all. Nevertheless, some potential approaches are showing initial promise.

Like other vaccines, an opioid inoculation would cue the body to generate antibodies—proteins normally associated with fighting diseases—only here they would be specifically directed against opioid molecules. Each vaccine would focus on only one type of opioid. Take heroin, for example: If someone received a heroin vaccine and then used the drug, instead of experiencing a high, the drug and its psychoactive metabolites would be quickly bound up by antibodies that would prevent them from reaching the brain. That would stop them from getting to receptors that might normally make the heroin user both feel good and also simultaneously depress breathing—the leading cause of overdose deaths. In short, an effective opioid vaccine could potentially save lives. Yet every opioid vaccine effort—dating back to the 1970s—has failed.

The most advanced opioid vaccine candidate is a heroin vaccine designed by scientists at The Scripps Research Institute. That team, headed by chemistry and immunology professor Kim Janda, recently published promising research showing the vaccine could neutralize varying doses of heroin in rhesus monkeys without any problematic side effects—making it the first opioid vaccine to get to that point. Four monkeys were given three doses of vaccine each. During the first month following vaccination the treatment helped block heroin’s effects, and it continued to provide some degree of protection for more than eight months. Notably, the vaccine only worked against heroin—not other opioids. Moreover, two of the monkeys that had also received the vaccine during an initial pilot study seven months earlier were better able to neutralize heroin’s effects after the second round of shots, which is good news—suggesting inoculations might be more effective with future booster shots. “We think we have a pretty good [drug] cocktail right now. Our confidence is bolstered by our nonhuman primate studies,” Janda says. But he notes that other vaccines, including one for cocaine, previously looked promising in animals but did not elicit high enough levels of antibodies to provide protection in humans.

Several other teams are developing candidate vaccines. Two separate drugs designed to combat prescription painkiller oxycodone and heroin have been in the works for years at the Minneapolis Medical Research Foundation (MMRF), but those vaccines are still only being tested in rodents. “For our group and others it will take years before we reach the market,” says Marco Pravetoni, who is co-leading the work at MMRF. Now his team is focused on manufacturing pharmaceutical-grade vaccines that would be eligible for U.S. Food and Drug Administration testing, and they are looking for possible industry partners to speed up the process to product development, he says.

Meanwhile, the U.S. Army also has another candidate heroin vaccine that it hopes to eventually couple with an experimental HIV vaccine it is working on—to simultaneously reduce disease and fight addiction. That vaccine, which is also in rodent testing, has been licensed to Opiant Pharmaceuticals —formerly Lightlake Therapeutics—the company that helped net FDA approval for the overdose antidote intranasal naloxone (Narcan), says Gary Matyas, chief of the Adjuvants and Formulations Section at Walter Reed Army Institute of Research and head of its opioid vaccine research.

Despite the seemingly slow progress, there have been significant improvements in opioid vaccine development in recent decades, says Ivan Montoya, acting director of the Division of Therapeutics and Medical Consequences at the National Institute on Drug Abuse (NIDA). “Newer vaccines are able to stimulate the immune system more efficiently,” he says. “So the production of antibodies is better than what it was in the past.” And historically, the holdup has not just been the technology of vaccine development, he notes. There were relatively effective medication-assisted interventions like methadone that also put opioid vaccine research on the back burner until relatively recently. “But right now the opioid crisis issue is going beyond the interventions we have,” he says, noting those medications are not always available or completely effective.

An option with more immediate promise than vaccine candidates may be introducing more options to treat withdrawal symptoms, Montoya says. The FDA is currently reviewing one treatment, lofexidine, which is already approved in the U.K. and will hopefully be approved in the U.S. “soon,” he says. The drug, which was partly supported by the NIDA, is being developed specifically for the treatment of opioid withdrawal syndrome—a troubling constellation of symptoms that can include body aches, racing heart, nausea and vomiting. Whereas medications like methadone or buprenorphine—which essentially trick the brain into thinking it is still getting the abused drug—can relieve the withdrawal symptoms and psychological cravings, if lofexidine is given a regulatory green light, “this will be the first and only medication approved by the FDA for the specific indication of treatment of opioid withdrawal,” Montoya says. (The FDA declined to comment on whether the drug was under review or its potential timing.) Right now there is also a third medication-assisted treatment called naltrexone, which can help neutralize heroin’s high but would likely not be as long-acting or cost-effective as a vaccine.

Opioid experts say they see other obvious benefits for vaccine development. “One of the advantages to a vaccine would potentially be compliance related—if the vaccine lasts several months, that person wouldn’t need to take a medication or treatment during that time,” says Stanford University anesthesiology professor David Clark, a member of the National Academies of Sciences, Engineering and Medicine committee that reviewed available opioid interventions and put out a report on how to combat the opioid crisis last month. Another benefit of inoculations, he says, might be that substance abusers may prefer them to methadone or buprenorphine—medical opioids that some people are reluctant to use because they believe they are trading one opioid addiction for another. (Unlike heroin, however, the medications are administered in a controlled setting at specific doses. They have gradual onset and produce stable levels of the drug in the brain—which NIDA says helps the cycle of drug crashes and cravings and helps reduce the desire to use opioids.)

But because the three experimental vaccine candidates from Scripps, the MMRF and the Army have not been used in humans, it is impossible to know how safe they would be and how they would operate in the real world. One major concern is if a person takes a heroin vaccine, he may turn to a different opioid for a high. That’s why, right now, there is a need to expand the use of available, proved techniques including medication-assisted treatments and counseling to help fight the opioid crisis, Clark says.

“Whether those vaccines will be truly effective—maintaining a high enough titer of antibodies against the illicit opioid to protect them from the drug—that’s quite a challenge. They may also be expensive and it seems they would require frequent revaccination and boosters,” Clark says. “I wouldn’t want to lose perspective on deploying what we have—which could be used more effectively—while just waiting on the promise of a vaccine.”