With overdoses at record highs, a veterinary tranquilizer spreading through the U.S. drug supply poses new threats

It was in the mid-2010s, the researchers heard, when “tranq dope” took off in Philadelphia.

They knew that “tranq dope” — opioids that contained the veterinary tranquilizer xylazine — was already a fixture in the drug supply in Puerto Rico and had sporadically turned up in overdose reports in Philadelphia as far back as 2006. But now, people who used drugs and sold drugs told the researchers that xylazine had become a sought-after substance, and it had become a much more prevalent element of the local drug supply.

The reports from Philadelphia and clues that xylazine was cropping up in other parts of the country inspired the researchers and colleagues to try to track the expansion of the drug across the continental United States. And in a paper published this month, they reported a steep jump in just a few years: In the 10 places studied, xylazine was found in 0.36% of overdose deaths in 2015. By 2020, it was 6.7%. In some places, it was appearing in 1 in 5 overdose deaths.

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“It’s been a structural shift, and it’s caught on,” said anthropologist Philippe Bourgois of UCLA, one of the authors of the paper and a member of the team who did the work in Philadelphia, which involved living for stretches in local neighborhoods to study drug markets, poverty, and violence.

Notably, the study found the powerful synthetic opioid fentanyl, which has come to dominate regional drug supplies, in nearly every xylazine-involved death as well, indicating it wasn’t just the tranquilizer that was causing these overdoses. Experts are still trying to understand the risks of xylazine, but they’re worried the drug — which is not an opioid but acts as a sedative — can increase the chances of a fatal overdose when combined with drugs like fentanyl because it can exacerbate the respiratory depression that opioids cause. It might also make it harder to reverse those overdoses with naloxone, which is designed to work on opioids.

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The study underscores several facets of the worsening U.S. overdose crisis, which is now killing more than 100,000 people a year. It highlights how adulterated — and in turn, increasingly dangerous — the drug supply has become. For example, fentanyl, once largely found in the supply of opioids like heroin, is now more frequently polluting stimulants like cocaine and methamphetamine. It also shows the lengths to which researchers have to go to keep up with the evolving drug supply, at a time when federal data can be outdated by the time they’re released.

“The drug supply is really a mess right now,” said Joseph Friedman, an addiction researcher at UCLA and the first author of the paper. “The number of contaminants is just spiraling out of control, and it’s really hard to keep track of. People are not buying what they think they’re buying, or they don’t know what they’re buying.”

Friedman said his instinct was generally not to be alarmist about emerging drug trends, given the hysteria that has historically accompanied drug use. But even as much more needs to be learned about xylazine, Friedman said early signs suggest it’s an “especially noxious contaminant that is spreading through the drug supply.”

The new study provides a more sweeping and contemporary look than past reports at what’s happening with xylazine in the continental United States. Many places don’t screen for it regularly, and federal drug and overdose data — whether from the Centers for Disease Control and Prevention or the Drug Enforcement Administration — are at best months old when released.

Last year, for example, the CDC published a short report about xylazine that mentioned how it had been found in overdose deaths in some two dozen states. But it looked only at 2019. Media reports and some state data also indicated that xylazine’s growth accelerated after that.

Without routine testing for xylazine, the researchers say, it’s proven difficult to get a handle on how significant the trend might be. To get a clearer picture, they both analyzed death records and incorporated ethnographic research, which involves embedding in communities over years and interviewing residents.

“This paper really shows the value of interrogating what’s going on,” said Magdalena Cerdá, the director of the NYU Center for Opioid Epidemiology and Policy, who was not involved in the new study. “It’s going to give you a much richer picture” of what’s happening with the drug supply, particularly for products that are just starting to take off, she said.

It’s crucial to know what’s in the local drug supply for public health agencies and harm reduction groups to respond with appropriate strategies. With xylazine, health officials might look at the data and warn people who use drugs and providers that overdose victims might need more than just a dose of naloxone. As Connecticut health officials wrote last year, “xylazine intoxication might require additional interventions and appropriate supportive measures, which include blood pressure support with intravenous fluids, atropine, and extended hospital observation because of cardiac effects.”

“Knowing what’s in the drug supply sooner would let us act faster,” said Chelsea Shover, an epidemiologist at UCLA and an author of the paper.

For the new study, the researchers compiled information from 10 medical examiners’ and coroners’ offices — from San Diego and Phoenix to Milwaukee and New Hampshire — that make public their data at a faster clip than the federal government. They found that while xylazine became more prevalent nationally from 2015 to 2020, there was regional variation, with much higher rates in the Northeast versus the West. Most recently, xylazine appeared in 10.2% of overdose deaths in Connecticut, 19.3% in Maryland, and 25.8% in Philadelphia.

The study also provides clues to why xylazine is spreading throughout the country. Fentanyl produces a powerful high, but the euphoric feelings are shorter-lived than those offered by other opioids like heroin. That means that people have to inject more frequently, which can be expensive, inconvenient, and risky. Adding xylazine, however, seems to give the fentanyl “legs,” meaning it extends the high. As one person quoted in the study said, xylazine “gives the dope more of a heroin effect, it’s a good rush.”

If that’s the case, then perhaps dealers are simply offering a product that their customers will like.

“This short duration of fentanyl creates demand for cuts that extend its action,” Friedman said.

It’s not just the increased overdose risk and the fact that xylazine-involved overdoses might resist naloxone that are alarming the research team. People who used drugs with xylazine seem to be more susceptible to wounds and infections on their skin and in other tissues. It’s not clear why, but it was noted by people in the community.

“I got some friends out here that got really torn up by it, you know they got holes in them, abscesses, basically it’s like the body is rotting,” one person told the research team. Or, as one harm reductionist interviewed for the study said, the arrival of xylazine is “when we started to see way more people coming in with necrotizing skin and soft tissue issues. The amount of medical complaints related to xylazine was pretty astounding and terrifying. Xylazine wounds are a whole other kind of …just horror.”

The team’s data also point to how U.S. overdoses have shifted over the past two decades. The culprits went from prescription opioids, to heroin, to fentanyl and other synthetic opioids, to now what’s called “polysubstance” use — meaning it’s not just opioids, but also drugs including stimulants and benzodiazepines, often used in combination. While fentanyl appeared in nearly all the xylazine-involved overdoses the team studied, there was also cocaine present in 45.4% of them, benzodiazepines in 28.4%, heroin in 23.3%, and alcohol in 19.7%.

Experts stress the term “opioid crisis” doesn’t reflect what’s happening in the country — at this point, it’s a far broader overdose crisis.

In their paper, the researchers warn that xylazine’s “growth is likely to have epidemiological significance in the coming years, following the trajectory of fentanyl’s spread across the country.” And since the study was published, there are already new signs of the drug’s presence. Last week, an overdose cluster in Austin killed two people and hospitalized roughly a dozen others. Local officials have said they suspect xylazine played a role. 

This story is part of a series on addiction in 2022, supported by a grant from the National Institute of Health Care Management. 

Source: STAT