December 05, 2022
Ever-changing trends in the nation's opioid epidemic have resulted in an increasingly tainted drug supply in the United States.
More than ever, drug overdoses are now linked to substances that have been mixed with fentanyl, the powerful synthetic opioid that has largely replaced heroin as the primary driver of drug dependency and death in the U.S.
In Philadelphia, the veterinary sedative xylazine, also known as "tranq," has become pervasive in drugs sold on the street. The anesthetic and pain reliever is used by vets to treat horses and cattle, yet the compound also is favored as a cutting agent in fentanyl because it can extend a person's perception of a high.
"Xylazine was initially added into the drug supply because a heroin high lasts for 6-8 hours, but a fentanyl high lasts from 1-2 hours," said Jennifer Shinefeld, a field epidemiologist for the Philadelphia Department of Public Health. "The tranquilizer was being added to mimic a traditional heroin high, but also to allegedly prolong the effects."
Among Philadelphia's 1,276 fatal overdoses in 2021 — the city's deadliest year on record — fentanyl was linked to 71% of fatalities. The drug was present in 94% of fatal overdoses in which opioids were found, showing the extent to which fentanyl has supplanted heroin as the predominant opioid.
But the emergence of xylazine as an additive is further complicating drug interactions in people who use these substances, requiring urgent changes to Philadelphia's public health response. The drug can cause painful wounds on the skin and may lead to respiratory problems that make reversing opioid overdoses more complex.
Tranq was found in 90% of the dope samples the city tested last year, according to the health department, which started routinely analyzing the city's drug supply in 2017 at the urging of grassroots advocates.
Better understanding which drugs are most commonly being used and mixed enables the health department to share those details, and information about the drugs' risks, with substance users and the community-based organizations and health care providers who help them.
"Xylazine is the primary adulterate (in the drug supply)," Shinefeld said. "I say that because we no longer consider fentanyl a primary adulterate, but (rather) the primary component. Fentanyl started to take over the drug supply in 2010. There's not very much heroin left. There are certain areas where you can still get it, but all of the bags that we've ever tested that had actual heroin also had fentanyl present in them."
Last year, xylazine was detected in more than 44% of fentanyl-involved overdose deaths in Philadelphia. It was found in 34% of overdose deaths across all categories — a 39% increase from 2020.
The unique problems that xylazine presents to drug users and medical practitioners in Philadelphia could be a sign of what's to come in other parts of the country, and an opportunity for the city to develop a response that can be implemented elsewhere.
Xylazine first emerged as a recreational drug in Puerto Rico during the early 2000s, years before fentanyl became a staple of the U.S. drug supply.
"It was seen among folks who were residing in towns where there was higher veterinary use of it," said Jewell Johnson, a substance use epidemiologist in Philadelphia's health department.
As fentanyl spread first in the Northeast, then westward over the last decade, xylazine came to be seen by drug suppliers as an appealing substance to offset the shorter run of a fentanyl high. The drug doesn't make opioids last any longer, but it prolongs the mental state of being on a drug.
Philadelphia, long an epicenter of the nation's opioid epidemic, became an ideal place for tranq dope to flourish.
"Outside of Puerto Rico, for lack of a better word, Philadelphia is ground zero for xylazine," Shinefeld said.
The health department has records of fatal overdoses involving xylazine that date back as far as 2006. By 2010, Shinefeld began hearing more from drug users who identified a tranquilizer that was becoming more common in the city's dope supply. The emergence of fentanyl around the same time accelerated the trend.
Tranq's infiltration of Philadelphia's fentanyl supply is upending established protocols for responding to opioid overdoses. Various groups that provide services to drug users are now compelled to pull together resources for treating xylazine wounds before they become severe.
Much like benzodiazepines, such as Xanax and Klonopin, xylazine acts as a sedative that depresses the central nervous system. This causes respiratory depression, making an opioid overdose more dangerous and more difficult to treat. First responders must take care to maintain a person's airway after administering naloxone, the reversal drug commonly known as Narcan, so that the person is able to breathe.
"From first-hand experience reversing overdoses for the last 12 years, back in the day, you could reverse someone and they would be awake and alert," Shinefeld said. "But because Narcan works on opioid receptors, it only removes opioids from those receptors. Xylazine is still present and active in the body. The individual is still sedated afterward."
In some cases, this may mean that a person who has overdosed still appears to be impacted by fentanyl. A first responder may believe that a second dose of Narcan is needed, rather than attending to the person's breathing difficulties.
"Narcan trainings have had to be adapted to make people aware of respiratory depression caused by xylazine — and the impact that will have on reversing an overdose," Shinefeld said. "I've done upwards of 20 minutes on someone for rescue breathing, which is exhausting. At a certain point, it's not productive for the individual, either."
Health department staffers now carry hand-held valve masks, called Ambu bags, that can be used to assist people who are struggling to breathe. One community organization in Philadelphia also carries oxygen tanks, although their high costs make them hard to use more widely.
People who use xylazine are known to suffer from immensely painful skin wounds that put them at risk of serious infections. Many users put off treatment because there are few paths that don't leave them in crippling withdrawal, especially at hospitals.
The medical explanation for xylazine wounds still isn't well understood, since the lesions don't appear in animals who are given the medication.
"There are a lot of hypotheses and ponderings around it, but it hasn't been studied enough in humans to know very much, or to know whether there is antibiotic resistance to related conditions, like hepatitis B and C, that might affect it," Shinefeld said.
I've seen tranq wounds heal when they're taken care of, and it's not something that heals quickly. It's not like a cut on the finger. They need repeated and consistent treatment. – Jennifer Shinefeld, Department of Public Health
Some research suggests that the ulcers and abscesses caused by xylazine use are related to the constriction of blood vessels, which impairs wound healing in the areas of skin that had an initial inflammatory response. The drug also may lead to blood iron and blood sugar deficiencies.
Xylazine wounds differ from the infections that can result from repeated drug injections. Often, tranq wounds surface on parts of the body other than where the drug was taken. They aren't caused by an infection, but they can become infected if left untreated for too long.
Shinefeld suggested that people on certain medications and those with already weakened immune systems may be more vulnerable to these wounds appearing and becoming infected.
"Somebody who's on hepatitis C medication, or has a condition that impacts the immune system," Shinefeld said.
Any method used to take the drug puts people who use it at risk.
"Xylazine wounds can occur no matter how the drug is taken — whether it's smoked, snorted or injected," Shinefeld said. "If someone injects, it doesn't necessarily occur at the site of injection. People who snort are getting more internal nasal and sinus issues, but they are still seeing these wounds pop up, too."
Last week, Stat News reported on Philadelphia's plight with xylazine and the wound treatment initiatives led by Savage Sisters, an outreach organization that has been providing services in Kensington, the city's hot spot for opioid addiction.
Savage Sisters offers wound care and fosters an environment where medical providers and drug users can discuss treatment tips and experiences. During a recent event at McPherson Square Park, one person with xylazine wounds lamented the damage the drug is doing.
"It's crazy this stuff, it's burning through our bodies," the person told Stat News.
Most wounds from xylazine can be successfully treated without turning to extreme measures, such as amputation. The sooner a wound is dressed, the more likely it is to heal.
"There's a lot of street-based medicine and amputation is always the last resort," Shinefeld said. "That's once the infection gets down to the bone. There are levels of antibiotic and self-care that people can do, which we're also working to adapt from clinical to streetside recommendations for treatment."
But there also are systemic issues that make wound treatment more challenging.
"People (with wounds) don't necessarily want to go to the hospital, but also there's a lack of environmental resources like clean water for people to wash their hands or have a sterile surface to take care of their own wounds," Shinefeld said. "I've seen tranq wounds heal when they're taken care of, and it's not something that heals quickly. It's not like a cut on the finger. They need repeated and consistent treatment."
Emergency department visits for skin and soft tissue injuries have more than quadrupled since the first quarter of 2019, according to the health department. Amputations are not as easy to track because they are coded differently by hospitals, which don't always have complete records.
Shinefeld said the health department's harm reduction team has hired a new wound care nurse and plans to bring on a part-time nurse practitioner. There also will be new informational material from the health department about wound care, overdose response and harm reduction practices related to xylazine.
Containing the impacts of xylazine on vulnerable populations is challenging for public health workers on a number of fronts.
Due to the drug's classification as a veterinary medicine and the ways it can be obtained or made independently, xylazine poses concerns similar to other substances that have gained traction in drug markets.
Although we aren't certain where xylazine is coming from, we have heard anecdotally that xylazine is being diverted from veterinary sources. – Jewell Johnson, Department of Public Health.
Unlike heroin and fentanyl, xylazine is not one of the U.S. Drug Enforcement Agency's scheduled controlled substances, which are treated differently in terms of prescribing guidelines and legal consequences for their production and possession.
The vast majority of states, including Pennsylvania, haven't made xylazine a controlled substance, either. In New York, xylazine is a schedule III depressant, and in Florida, it's a schedule I controlled substance because it has no medically approved use in humans. These are the only states that have made the drug a controlled substance.
But scheduling illicit substances, a pillar of the DEA's War on Drugs, isn't a magical fix by any means. It often leads to other, potentially more lethal problems.
"There are dangers in talking about limiting, monitoring and scheduling xylazine because it is so prevalent in the drug supply," Shinefeld said. "People are dependent on it at this point because of the withdrawal and detox management, and everything that goes with it. The idea of scheduling is not even putting a band-aid on it. It's opening up a whole pipeline for something else to jump in and be more dangerous."
Fentanyl, originally developed pharmaceutically as an intravenous anesthetic, was made a schedule I drug by the federal government in response to its proliferation as a deadly and addictive recreational drug. Illegal drug producers since have made their own fentanyl-related compounds, such as carfentanil, that are often more potent than those originally placed under tighter federal control.
"Fentanyl was scheduled, and now there are 150-plus fentanyl analogs to get around scheduling," Johnson said.
Fentanyl also has made the business of drug distribution easier and more profitable. The cost of heroin manufacturing, which relies on the poppy plant, is much higher than the cost of making fentanyl synthetically. And because it's more potent, the fentanyl supply can be spread more widely at better margins.
Xylazine's path into Philadelphia and other drug markets, including cities along the East Coast and in Chicago and Texas, is not yet as clear as fentanyl's rise in the United States. This is partly because of its veterinary status, which means it's prescribed to animals and isn't tracked in drug surveillance systems like the Prescription Drug Monitoring Program. Scheduling the drug would not change that.
"Although we aren't certain where xylazine is coming from, we have heard anecdotally that xylazine is being diverted from veterinary sources," Johnson said. "Scheduling something just means making it more difficult to access. It potentially becomes more dangerous because then folks are creating things in less controlled conditions."
In veterinary medicine, xylazine is uniform and dosed appropriately. In a bag of dope, there's no uniform dosage. People who use it can become dependent on it, much like people can form addictions to benzodiazepines, in addition to the opioid addiction that first exposes a person to fentanyl.
"We don't see intentional, xylazine-only fatalities in Philadelphia," Johnson said.
The health department can detect the difference between xylazine samples that appear to be diverted from veterinary sources and those that come from the black market.
"One of the ways we're able to monitor the sourcing and potency of the xylazine is the cut," Johnson said. "Purity of veterinary xylazine is 40-60%. Some of the black market analogs are upwards of 99% pure."
Shinefeld said she is opposed to the scheduling of xylazine because it perpetuates a punitive approach to addictions.
"The drugs are dangerous because of how they're made and people don't know what they're getting," Shinefeld said. "The movement needs to be pushed toward a safe supply, so that individuals know what they're taking, can appropriately dose and not have concerns about additional adulterates or additives. The conversation really needs to be moved to how do we protect the people who are using substances, and that way it's not punitive scheduling. It's providing them with what they need and what they want."
The health department has a hospital advisory committee that meets to discuss issues related to trends in drug use, including xylazine. Shinefeld urges caretakers to be aware of the complete picture of patients who seek treatment for conditions related to xylazine.
"We're advocating for changes in detox management and protocols, as well as comfort care given to individuals who are seeking medical care, but not necessarily (addiction) treatment," Shinefeld said. "With detox, there is a lot of irritation and agitation. People can also be put at risk of having seizures coming off of (xylazine), the same way you would if you're detoxing off of benzodiazepines."
The PDMP is used to track scheduled drugs like benzodiazepines, opioids, stimulants and muscle relaxants. Hospitals monitor prescribers to prevent certain patients from obtaining drugs that pose greater risks for addiction.
"Because of the PDMP, everyone gets a scorecard now at the hospitals," Shinefeld said. "Care needs to be patient-first in all settings, which means providing the appropriate comfort meds. That may make the scorecard go above the average, but you're keeping your patients comfortable enough while they're there for the cure that they need. If it means 'over-prescribing' benzos to keep someone comfortable — and not anxious — then that's what needs to happen."
Shinefeld noted that people who use fentanyl cut with xylazine will immediately go into opioid withdrawal after receiving Narcan. That will be compounded by withdrawal symptoms related to xylazine.
"If someone steps into an emergency department in Philadelphia, the assumption should be made that this person is also xylazine-dependent and should be treated as such," Shinefeld said.
Xylazine is far from Philadelphia's only concern when it comes to fentanyl-related overdoses, particularly in combination with other drugs. Stimulants such as cocaine and methamphetamine also have become increasingly linked to fatal overdoses, appearing in two-thirds of such fatalities last year. There has been a higher rate of fatal overdoses among Black residents in the city since the start of the COVID-19 pandemic, possibly because cheaply produced fentanyl has found its way into more non-opioid drugs of choice.
The long and complex push for an overdose prevention site in Philadelphia also remains tied up in federal court. The U.S. Department of Justice this week requested another extension to the lawsuit filed by Safehouse, the nonprofit that aims to create a haven for people to inject drugs under medical supervision, receive care for overdoses and be directed to resources for substance use disorder treatment at a centralized location. The winding litigation began nearly four years ago, and past exploration of possible locations for such a facility have been contentious.
Mayor Jim Kenney's office, which has supported an overdose prevention site in Philadelphia, reiterated that goal on Tuesday.
"As this crisis takes more lives and continues to evolve, we believe it is critical to use every available method to save lives and that an overdose prevention center would add a powerful tool to our existing harm reduction strategies," said Sarah Peterson, a spokesperson for Kenney. "Overdose prevention centers save lives, prevent injuries and illness, reduce drug use and drug-related litter in public spaces, and increase connections to health services and treatment."
The administration wants the litigation resolved in the near future to enable the city and its partners to move forward.
"If a settlement is reached, the city will work with Safehouse and the federal government to support a safe and effective operation, and we are committed to participating in a robust community engagement and outreach process as these discussions progress," Peterson said.