By Matthew Perrone
AP Health Writer
WASHINGTON 鈥� A powerful animal sedative in the illicit drug supply is complicating the U.S. response to the opioid crisis, scrambling longstanding methods for reversing overdoses and treating addiction.
Xylazine can cause severe skin wounds, but whether it is leading to more deaths 鈥� as suggested by officials in Washington 鈥� is not yet clear, according to health and law enforcement professionals on the front lines of efforts in New Jersey, New York and Pennsylvania. In fact, early data suggests the drug may inadvertently be diluting the effects of fentanyl, the synthetic opioid behind most overdose deaths.
There is broad agreement, however, that much more information is needed to understand xylazine鈥檚 impact, and to develop medicines to reverse its effects.
鈥淲e don鈥檛 know whether xylazine is increasing the risk of overdose or reducing the risk of overdose,鈥� said Dr. Lewis Nelson of Rutgers New Jersey Medical School, who advises federal regulators on drug safety. 鈥淎ll we know is that there are a lot of people taking xylazine and a lot of them are dying, but it doesn鈥檛 mean that xylazine is doing it.鈥�
In almost all cases, xylazine 鈥� a drug for sedating horses and other animals 鈥� is added to fentanyl, the potent opioid that can be lethal even in small amounts. Some users say the combination, dubbed 鈥渢ranq鈥� or 鈥渢ranq dope,鈥� gives a longer-lasting high, more like heroin, which has largely been replaced by fentanyl in U.S. drug markets.
Like other cutting agents, xylazine benefits dealers: It鈥檚 often cheaper and easier to get than fentanyl. Chinese websites sell a kilogram for $6 to $20, no prescription required. Chemicals used to produce fentanyl can cost $75 or more per kilogram.
鈥淣obody asked for xylazine in the drug supply,鈥� said Sarah Laurel, founder of Savage Sisters, a Philadelphia outreach group. 鈥淏efore anybody knew it, the community was chemically dependent on it. So now, yes, people do seek it out.鈥�
From a storefront in Philadelphia鈥檚 Kensington neighborhood, Laurel鈥檚 group provides first aid, showers, clothes and snacks to people using drugs.
Xylazine鈥檚 effects are easy to spot: users experience a lethargic, trance-like state and sometimes black out, exposing themselves to robbery or assault.
鈥淚t鈥檚 a delayed reaction, I could be walking down the street, it鈥檚 45 minutes later,鈥� says Dominic Rodriguez, who is homeless and battling addiction. 鈥淭hen I wake up, trying to piece together what happened.鈥�
[REALTED: White House warning: What you need to know about xylazine]
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U.S. regulators approved xylazine in 1971 to sedate animals for surgery, dental procedures and handling purposes.
In humans, the drug can cause breathing and heart rates to drop. It鈥檚 also linked to severe skin ulcers and abscesses, which can lead to infections, rotting tissue and amputations. Experts disagree on the exact cause of the wounds, which are much deeper than those seen with other injectable drugs.
In Philadelphia, the drug鈥檚 introduction has created a host of new challenges.
Naloxone, a medication used to revive people who have stopped breathing, doesn鈥檛 reverse the effects of xylazine. Philadelphia officials stress that naloxone should still be administered in all cases of suspected overdose since xylazine is almost always found in combination with fentanyl.
With no approved reversal drug for xylazine, the Savage Sisters group has taken to carrying oxygen tanks to help revive people.
Meanwhile, a roaming van staffed by local health workers and city staffers aims to treat the skin wounds before they require hospitalization.
The wounds can make it harder to get people into addiction treatment programs, which typically don鈥檛 have the expertise to treat deep lesions that can expose tissue and bone.
鈥淚f you have someone out there who鈥檚 ready to come in for treatment, you really want to act on that quickly,鈥� said Jill Bowen, who runs Philadelphia鈥檚 behavioral health department.
The city recently launched a pilot program where hospitals treat patients for wounds and then directly transfer them to addiction treatment.
Xylazine can be addictive and patients who stop taking it report severe withdrawal symptoms, including anxiety and distress. There鈥檚 no approved treatment but physicians have been using the blood pressure-lowering drug clonidine, which is sometimes prescribed for anxiety.
In April, federal officials declared xylazine-laced fentanyl an 鈥� ,鈥� pointing to the problems in Philadelphia and other northeastern cities. Testing is far from uniform, but the drug has been detected in all 50 states and appears to be moving westward, similar to earlier waves of drug use.
Officials describe the drug鈥檚 toll in stark terms and statistics: increased more than 1,200% percent between 2018 and 2021. But that largely reflects increased testing, since most medical examiners weren鈥檛 looking for the drug until recently.
鈥淲hat it is doing is making the deadliest drug we鈥檝e ever seen, fentanyl, even deadlier,鈥� Anne Milgram, head of the Drug Enforcement Administration, told attendees at a recent conference.
But those who have studied the problem closely aren鈥檛 so sure.
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One of the only studies looking at the issue reached a startling conclusion: People who overdosed on a combination of fentanyl and xylazine had 鈥渟ignificantly less severe鈥� outcomes than those taking fentanyl alone.
It was the opposite of what Dr. Jennifer Love and her colleagues expected, given xylazine鈥檚 dangerous effects on breathing. But their analysis of more than 320 overdose patients who received emergency care found lower rates of cardiac arrest and coma when xylazine was involved.
Love, an emergency medicine physician at New York鈥檚 Mount Sinai hospital, suggested xylazine may be reducing the amount of fentanyl in each dose. She stressed that this is only one possible explanation, and more research is needed into xylazine鈥檚 long-term effects. She also noted that the study didn鈥檛 track downstream effects of xylazine that could be deadly, including skin infections and amputations.
But hints that xylazine could be blunting fatal overdoses are showing up elsewhere.
In New Jersey, about one-third of the opioid supply contains xylazine, based on testing of drug paraphernalia. But less than 8% of fatal overdoses involved xylazine in 2021, the latest year with complete data.
Police Capt. Jason Piotrowski, who oversees the analysis of state drug data, said xylazine鈥檚 ability to extend users鈥� high may be a factor in why it鈥檚 showing up less than expected in fatal overdoses.
鈥淚f xylazine is lasting longer and that鈥檚 why people are using it, then they鈥檙e not going to need as many doses,鈥� he said. 鈥淪o now their exposure to the more deadly fentanyl decreases.鈥�
Like other experts, Piotrowski stressed that this is only one theory and xylazine鈥檚 impact is far from clear.
Philadelphia officials see no upside to the drug.
鈥淚 don鈥檛 frankly see a plus side to xylazine,鈥� said Dr. Cheryl Bettigole, the city鈥檚 health commissioner. 鈥淚t seems to increase the risk of overdose and it causes these severe, debilitating wounds that interfere with people鈥檚 ability to get into treatment.鈥�
Philadelphia鈥檚 annual toll of fatal overdoses has climbed by 14% since xylazine became a significant part of the local drug market around 2018. In 2021, the city reported 1,276 overdose deaths. Bettigole expects final 2022 figures to show another increase.
More than 90% of lab-tested opioids in Philadelphia contain xylazine, according to city figures.
Even as Savage Sisters and other advocates deal with xylazine鈥檚 toll, they are seeing newer drugs circulate, including nitazenes, a synthetic opioid that can be even more potent than fentanyl.
A shifting mix of opioids, stimulants and sedatives has come to define the U.S. drug epidemic, making it harder to manage a crisis that now claims .
The Biden administration and Congress are considering changes to try to limit xylazine prescribing and distribution.
But past restrictions didn鈥檛 solve the problem: When regulators cracked down on painkillers like OxyContin, people largely shifted to heroin and then fentanyl.
鈥淔irst we had pills, then we had heroin and then we had fentanyl,鈥� Piotrowski said. 鈥淣ow we have everything. And xylazine is just a part of that.鈥�
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AP journalists Tassanee Vejpongsa and Matt Rourke in Philadelphia contributed to this story.
The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute鈥檚 Science and Educational Media Group. The AP is solely responsible for all content.