As the opioid crisis continues along its destructive path, a new factor has entered the fray to make drugs more lethal: xylazine. The drug, which is also known as “tranq,” has traditionally been used in veterinary practice as a tranquilizer but is now being mixed with fentanyl, placing people who use drugs at a higher risk of adverse effects.
Joshua DeBord, PhD, senior scientist at the Center for Forensic Science Research and Education, suspects that tranq is added to fentanyl to do one of three things: “Increase the euphoria, increase the sedation, or increase the potential addiction,” he said. It’s also possible that makers of the drug believe it somehow prevents overdoses caused by fentanyl when used in combination.
The mixture of fentanyl and tranq, like other emerging novel psychoactive substances (NPS), is also created to avoid detection, said Harvey W. Kaufman, MD, medical director and head of the Health Trends research program at Quest Diagnostics. “We’re seeing a shift towards these synthetic drugs that are being developed by innovative chemists as a way to evade detection through traditional drug testing.”
A GROWING PROBLEM IN U.S. DRUG SUPPLY
In a recent report, Quest Diagnostics found xylazine in nearly 1 in 12 samples of fentanyl, making it the most popular NPS drug in the U.S., particularly in the eastern part of the country. Five percent of those samples were positive for other NPS drugs.
In addition, Quest found that 37.7% of fentanyl-positive specimens were also positive for xylazine, and that 97.7% of specimens positive for xylazine were also positive for fentanyl. “They’re so common already everywhere that no one’s immune at this point. Every part of the country has been exposed to relatively high levels of these NPS drugs,” Kaufman said.
Because xylazine is still relatively new in the drug market, it can be hard to recognize and treat — and it’s having devastating effects. Because it’s not an opioid, Narcan doesn’t work in reviving people, and thexylazine injection itself can also cause recalcitrant skin ulcers and gruesome necrotic wounds.
Xylazine has never been studied clinically in humans, so it’s still a mystery just how much of the drug is required to cause terrible consequences, said Adina Badea, PhD, DABCC, director of toxicology at Rhode Island Hospital and assistant professor of pathology and laboratory medicine at the Warren Alpert School of Medicine at Brown University. For example, “we don’t know how much xylazine it takes for someone to develop skin ulcers,” she said. People who use xylazine can also have an “almost sleep-like sedation, they can collapse in an uncomfortable position,” she said, which can lead to compartment syndrome, requiring limb amputation. “There’s a lot we don’t know.”
TESTING FOR XYLAZINE IN THE CLINICAL LAB
Although xylazine was designed to evade drug tests, clinical laboratorians have been catching up. “We’ve seen significant utilization, more than we anticipated,” Jennifer Colby, PhD, DABCC, FADLM, scientific director at Premier Biotech, said of her company’s test. Most of their customers are coming from the addiction treatment and substance use disorder space. They perform liquid chromatography-mass spectrometry to test for the presence of xylazine and related metabolites.
Like Quest, Premier Biotech found that not all fentanyl contains xylazine, but “when xylazine is present, fentanyl is almost always present,” Colby said.
That can help avoid unnecessary testing when xylazine is unlikely to be present. “In terms of testing, we get a lot of orders for xylazine on people who have no history or no recent history of fentanyl use. If the fentanyl screen is negative, the xylazine screen almost always is going to be,” Colby said.
Rhode Island Hospital offers a comprehensive drug screen for xylazine in urine and serum with liquid chromatography-high resolution mass spectrometry, said Badea. “The nice thing about an untargeted method on a high-resolution mass spectrometry platform is that you can very easily add compounds to the list that you are monitoring,” she said.
Still, it took some time for the test to catch on with emergency department physicians, and to educate clinicians about xylazine and how it might present. “Mass spec assays in general take a longer time to perform, because they have a relatively intense sample prep, so we wait to batch samples — although this assay was designed to be faster,” she said, with results taking 1−2 hours once the sample arrives at the lab.
Over time, physicians began to use the test more as they became more familiar with it, saw more people being affected by xylazine, and realized they could still deliver results to patents after they were discharged, she said.
The first adopters of their test were pediatric physicians “because kids get into everything,” she added. “A lot of the times with kids, the amounts of drug present are not high enough to trigger a positive result on a typical immunoassay drug screen, even if they are exposed to a drug the test is designed for. But the clinical impact is still profound, so this is where a mass spec test with increased sensitivity, specificity, and a more comprehensive panel can be really impactful.”
Modern clinical and toxicology labs have the equipment to test for xylazine, said DeBord. “There is nothing especially challenging about the compounds, but labs must make the financial investment to expand their testing capabilities,” he said, adding that he believes it may not be worth the investment if a lab is already testing for fentanyl and there is no established use of xylazine in the area.
WORKING IN THE PUBLIC HEALTH SECTOR TO TEST FOR XYLAZINE
While collaborating with physicians is important for xylazine testing, so is partnering with the professionals who interact the most with drug users.
“There’s an opportunity for significant interplay between the people who are doing the testing in biological samples and the people at the front lines doing harm reduction work, where they’re providing xylazine test strips so that users can test their actual drugs,” said Colby. County health departments also have a lot of information on what’s being found in drugs, which can help “to determine if it’s appropriate to offer a xylazine urine test.”
Rhode Island Hospital is part of a 2-year program called testRI that tests used equipment, such as pipes and syringes, which are donated from community members or local organizations. In the first published results, which appeared in the International Journal of Drug Policy and involved 125 samples, they found fentanyl in 67.2% of samples and xylazine in 41.6% (2023; doi: 10.1016/j.drugpo.2023.104118).
But they don’t just publish those results in medical journals. Instead, the Rhode Island Department of Public Health publishes test results for specific samples, anonymously, every 2 weeks on the Prevent Overdose RI website (https://preventoverdoseri.org/local-drug-supply/#tests).
“Some participants told us they showed their testing results to their sellers,” said Badea.This information is critical “to inform people that the drug supply is a lot more dangerous than it used to be, and they should be taking some precautions before they use, such as not using alone,” she said.
THE FUTURE OF NPS DRUGS
While the medical and laboratory community is now aware of the xylazine problem, it’s not the only NPS drug, and may not be the most common one for long. Which drugs are used most changes quickly. For example, in their report, Quest found that the rate of heroin-positive samples dropped off to 0.4% in 2022. Their data suggests that fentanyl’s superior potency and lower cost is pushing heroin out of the nation’s drug supply.
“This is going to continue to evolve,” Kaufman said. “We’re going to continue to look at other compounds that are going to be identified in the ensuing months and years, and modify our test offerings, as we’ve done over time to meet what’s actually being used.”
The harm reduction movement needs to continue to be a key player too, said Colby, since these professionals see the effects of drugs firsthand. “There’s a potential to partner with people on the front lines who know what’s going on with users, whereas we’re measuring downstream,” she said.
Clinical laboratorians should also stay on top of NPS trends in other geographic areas, which might indicate that a new drug is going to hit their market soon. Badea, for example, said she first learned about xylazine by reading news reports of what was happening in the substance use disorder community in Philadelphia. Then, she said, “with untargeted data collection on high resolution mass spec platforms you can retroactively survey your data to see if this has been present in your patient samples, but you just weren’t seeing it because you didn’t know to look for it.” If so, you can add that compound to the list of drugs you’re testing for. “I find it very useful to further keep up with how the drug supply is changing, and how fast it’s changing.”
Jen A. Miller is a freelance journalist who lives in Audubon, New Jersey. +Twitter: @byJenAMiller