Here’s what you should know about xylazine, also known as “ Tranq” or zombie drug , the veterinary tranquilizer increasingly found in illicit samples of fentanyl.
Don’t expect to find illicit drugs or designer knockoffs here. Instead, said Ashburn, director of pain medications at Penn Medicine, wheelchairs, crutches and antibiotics are the hot products.
The blame lies with xylazine or, as it is commonly called, “tranq” . Veterinarians have used the sedative and pain reliever for half a century, but it has never been approved for human use . And yet, it is increasingly detected in America’s illicit drug supply from coast to coast, usually combined with fentanyl or heroin , and in drug overdoses.
Xylazine "probably for many different reasons causes deep tissue injury , not only at the injection site, but also in places remote from the injection site," Ashburn explained in an interview. The sores and skin ulcers associated with the drug have earned it another nickname: zombie drug . Wounds associated with xylazine can be so deep that they expose tendon and bone, requiring amputation and spurring demand for wheelchairs and crutches.
Xylazine is thought to cause skin ulcers due to its vasoconstrictive effect and resulting decreased perfusion. Prolonged use can lead to poor wound healing, resulting in a higher chance of infection, the authors wrote.
Although the potentially fatal effects of xylazine in humans (including central nervous system and respiratory depression, significantly decreased heart rate, and low blood pressure) resemble those caused by opioids, it is not a opioid, so naloxone does not reverse its effects .
In April, the White House Office of National Drug Control Policy (ONDCP) officially designated fentanyl combined with xylazine as an "emerging threat to the United States ," and last November, the U.S. Food and Drug Administration The US (FDA) warned doctors about the serious effects of xylazine and provided suggestions on how to handle suspected overdoses of the drug. The FDA noted that veterinarians regularly use yohimbine hydrochloride and tolazoline hydrochloride to reverse the effects of xylazine in animals, but the drugs are not known to be safe and effective treatment options for xylazine-related overdoses in humans.
“Xylazine is making the deadliest drug threat our country has ever faced, fentanyl, even more deadly,” said Anne Milgram, JD, administrator of the US Drug Enforcement Administration (DEA). ., in a March public safety alert.
Here’s what you should know about this growing public health problem.
What is xylazine?
The drug is a central α2 adrenergic receptor agonist that causes a rapid decrease in the release of norepinephrine and dopamine in the central nervous system, according to the FDA. It is structurally similar to levamisole , a veterinary drug that was at one time approved for human use but is no longer approved; clonidine , used to treat hypertension in humans and, infrequently, also involved in overdoses; and tizanidine , used as a muscle relaxant in patients with multiple sclerosis or spinal cord injuries.
Xylazine comes in liquid form for veterinary use, but can be converted into salt or dried into a powder, which can be mixed with other powders or compressed into pills for illicit use, the New York State Department of Health explained in a brochure for the clinicians. Currently, xylazine is not a federally controlled substance. However, in late March, bipartisan legislation was introduced in both the Senate and House to change that.
“Drug traffickers are doing everything they can to increase their profits with dangerous drugs like tranquilizers, and we must empower law enforcement to crack down on their spread in our communities,” said Senator Catherine Cortez Masto ( D, Nevada), one of the sponsors of the legislation, said in a statement. Ahead of congressional action, nearly a dozen states have already added or are moving to add xylazine to their lists of controlled substances, according to a veterinary medicine website.
When did xylazine enter the illicit drug supply?
The first reported illicit use of xylazine dates back to 2001 in Puerto Rico, where it was combined with a stimulant and an opioid to make "speedballs ," explained a paper co-authored by ONDCP Director Rahul Gupta, MD, MPH, and Ashburn, 2 weeks after ONDCP designated the drug as an emerging threat. About a decade later, xylazine was documented as a drug of abuse on its own in Puerto Rico and continues to be so, the DEA noted in a report last October.
Philadelphia is considered by many to be the epicenter of this drug, which was first detected there in 2006, according to an update from the Philadelphia Department of Public Health last December. The department noted that “people who use illicit opioids in Philadelphia are almost certainly exposed to xylazine . ” In January of this year, xylazine was found in every street sample of opioids tested by the department, Ashburn noted.
Chicago began tracking xylazine in 2019 through the toxicology of fatal drug overdoses, Maryann Mason, PhD, associate professor of emergency medicine at Northwestern Feinberg School of Medicine, said in an interview; Not all jurisdictions perform routine xylazine testing in postmortem toxicology, according to the DEA. In California, xylazine was found in drug samples this year in Los Angeles, San Diego and San Francisco, a March health alert from the Los Angeles Department of Public Health noted.
In late February, the FDA issued an import alert restricting the illegal importation of xylazine. According to the alert, FDA staff can detain shipments of xylazine or finished pharmaceutical products containing xylazine without examining them. As the DEA noted in its October report, suppliers in China sell xylazine powder online at a low price.
How common is "tranq" in the US?
In its December update, the Philadelphia Department of Public Health warned that xylazine, called a "tranquilizer drug" when combined with opioids, increases the risk of mortality associated with opioid overdoses. “Almost all fatal overdoses with xylazine on board involve fentanyl,” Mason noted.
The full extent of U.S. overdose deaths involving xylazine is unknown. But it is clear that the use of xylazine is increasing, as is the number of overdose deaths in which it is involved. Research shows that these deaths have spread westward across the country, with the greatest impact in the Northeast, according to the National Institute on Drug Abuse. In 2020, about 26% of overdose deaths in Philadelphia involved xylazine, the highest prevalence in the U.S., researchers reported in 2022. Maryland had the second-highest prevalence, at 19%, followed by Connecticut with 10%.
More recently, researchers found that a high percentage of samples collected at 8 Maryland syringe services programs between November 2021 and August 2022 tested positive for xylazine. According to an article published in April of this year in the Morbidity and Mortality Weekly Report.
Nationally, xylazine was identified in forensic toxicology samples from 36 of 49 states analyzed in June 2021, according to the article by Gupta and Ashburn. And in the DEA’s recent security alert, Milgram noted that his agency had seized xylazine and fentanyl mixtures in 48 of 50 states and that approximately 23% of fentanyl powder and 7% of fentanyl pills seized in 2022 They contained xylazine.
Jennifer Love, MD, assistant professor of emergency medicine at the Icahn School of Medicine at Mount Sinai in New York, was first author of a study of 321 adults who sought care for an opioid overdose between September 2020 and August 2021. at any of 9 participating emergency departments spread across the US.
She and her co-authors found that nearly 3 in 10 patient serum samples tested positive for xylazine. In 1 of the xylazine-positive patients, methadone was the opioid involved; the other 89 tested positive for fentanyl or a fentanyl analog. None tested positive for the combination of xylazine and heroin. The study is ongoing, Love said in an interview.
Why has xylazine been added to opioids?
Although experts don’t know for sure, Ashburn offered his best guesses as to why xylazine entered and continues to be used in the illicit drug supply.
Initially, distributors might have started adding the drug as a bulking agent and then continued to do so because it enhanced the effects of fentanyl, reducing the frequency of injections, he said.
“It’s cheap and unregulated,” Mason explained. “People want it because the fentanyl high lasts very little and the impact is very strong. [Xylaxine] can prolong the effects of the opioid longer.” However, Love said, many of his emergency department overdose patients have never heard of tranq or don’t know if it is in their medication supply, so he tries to educate them about it.
The desire to differentiate their product from that of the competition may have motivated providers to start adding xylazine to fentanyl, clinical psychologist Adam Leventhal, PhD, director of the Addiction Sciences Institute at Southern University, said in an interview. California.
But, as Leventhal noted, "in places like Philadelphia, where xylazine mixed with fentanyl has been around for a while, there are probably people using [fentanyl] who now want the combination."
Can illicit drug users detect if xylazine is present?
People cannot tell if xylazine is in their medication sample just by looking at it. However, BTNX, a biotechnology company in Pickering, Ontario, recently developed rapid test strips to detect xylazine in liquid or powder. The strips sell for $3 each in the U.S., triple the cost of the company’s fentanyl rapid test strips, although the distributor’s website notes that special pricing is available for nonprofit organizations.
Validation testing conducted by the Suburban Philadelphia Forensic Science Research and Education Center, in collaboration with the Philadelphia Department of Public Health, found that BTNX xylazine test strips demonstrated high sensitivity and accuracy, allowing makes it acceptable for drug control purposes. Mason called xylazine test strips “a new but essential tool in the harm reduction toolbox.”
She is the principal investigator for Block by Block, an overdose death prevention initiative in Illinois. Block by Block trains residents and organizations in areas with a high number of overdose deaths to identify signs of overdose, administer naloxone, and use fentanyl test strips. The initiative is now in the process of purchasing xylazine test strips for use by outreach workers, Mason said.
Does xylazine change the treatment of opioid overdoses?
Emergency departments are not testing patients with opioid overdoses to see if xylazine was involved. “We don’t routinely do toxicology on people who overdose because it doesn’t really change the treatment modality,” Mason explained.
Naloxone should be given to everyone with a suspected opioid overdose, whether or not xylazine is involved, experts agree .
“The message needs to be consistent that naloxone saves lives, that naloxone improves the risk of death and other consequences of the contribution of opioids,” Leventhal said.
Because of the increasing likelihood that xylazine is involved, patients treated with naloxone should be monitored longer than before tranq appeared , Mason said. That’s because naloxone could revive them, but if xylazine is present, they could lose consciousness again, she explained.
“I heard stories from our own emergency department at Northwestern,” Mason said. Naloxone revived patients who then checked out, only to return to the emergency department with another apparent overdose, even though they had not used drugs since their previous trip to the hospital. “The first time this happened, it gave people pause.” Because xylazine could be involved, people receiving naloxone outside the hospital should still go to the emergency department for ongoing monitoring, Mason recommended. “It’s the safest thing to do.”
In Philadelphia, Ashburn said, resuscitation protocols for first responders are being modified to reflect the high prevalence of xylazine. When xylazine is involved in an overdose, patients may need additional support such as supplemental oxygen, fluid resuscitation to raise blood pressure, and airway monitoring to improve breathing.
Additionally, since xylazine can cause severe necrotic lesions on the skin anywhere on the body, when an overdose is suspected, "we now have a greater responsibility to completely undress the patient" and provide wound care supplies if necessary. Love noted.
In their study of overdose patients, those who tested positive for xylazine were unexpectedly less likely than those who tested negative to experience cardiac arrest requiring cardiopulmonary resuscitation or coma within 4 hours of arriving at the emergency department. One possible explanation is that xylazine replaced some of what would have been a fatal amount of fentanyl, Love noted, adding that she and her co-authors only knew which drugs the patients had used, not how much. "It’s very concerning," Mason said of xylazine in the illicit drug supply, "but we’re not without hope, and we’re not without the tools to address it."
