In late 2020, when he was still homeless in Kensington, James Sherman realized the drugs that kept him on the street were changing.

Sherman’s drug of choice was fentanyl. The powerful synthetic opioid burst onto the Philadelphia drug scene in the mid-2010s and quickly replaced most of the city’s heroin — once considered the cheapest and purest in the country. Fentanyl is a killer, causing a wave of fatal overdoses here as early as 2015. But soon, it was practically the only option for heroin users in the city. The drug users who survived it became tolerant, and then dependent, on the stronger opioid.

But by 2020, the fentanyl that Sherman had used on and off for the previous six years was changing, too. “I liked fentanyl, but I couldn’t find it. I would go to my normal spot, do a shot, and then get knocked out,” he said.

The drug that was causing him to black out is known on the street as “tranq” — xylazine, a powerful animal tranquilizer now contaminating most drugs advertised as fentanyl or heroin.

“It’s the same pattern of people who went through that transformation — who traditionally used heroin, that then became fentanyl,” Sherman said. “Now there’s people who don’t want tranq, they only want fentanyl. But you’re not going to find a bag without tranq.”

The situation has doctors, public health officials, advocates, and drug users united in fear. Xylazine isn’t an opioid, but it also depresses respiration and can’t be reversed with naloxone, making it harder to save people overdosing on xylazine-fentanyl combinations. Fentanyl overdoses can be tougher to reverse than heroin, and have driven death rates up for years. It’s not clear whether xylazine is causing overdose deaths on its own: A fourth of overdose victims in 2020 had xylazine in their systems, but mostly in combination with fentanyl, researchers recently found.

For people who have become physically dependent on tranq — often unknowingly — withdrawal can be painful. What’s more, traditional opioid withdrawal medications don’t help, making it even harder to seek treatment and stay in it.

Intravenous drug users often contend with skin infections at the site of injections. But with xylazine, severe lesions can appear anywhere on the body. Sherman remembers finding a small wound on his leg — where he never injected drugs — that took months to heal.

“I would inject in my neck, but these wounds were coming out on my hands and legs. It would scab up, and you would rip the scab off and it would be like a crater under your skin, like it’s eating your flesh,” he said. “I was like, What am I putting in my body?

Antibiotics — and, eventually, recovery after a stint in jail — allowed those wounds to heal. But he still has the scars — thick, round, raised patches of pale tissue on his legs and hands.

Sherman has been sober for 14 months, and now works as a house manager for Savage Sisters, a nonprofit that runs four recovery homes in South Philadelphia and outreach operations in Kensington. He’s grateful to be on the other side of his addiction, and sees his outreach work as a way to give back. But it’s difficult, he says, to encounter friends he lived with on the street, to see their wounds, to understand what’s happening to them.

“To see these guys wither away, more and more, is probably the hardest part,” he said.

`It causes people to black out’

When Philadelphia’s health department began a drug-testing program in the fall of 2020, it quickly realized that the city’s volatile drug supply was changing again.

“We haven’t had a single dope sample we sent out that hasn’t had xylazine in it at this point,” said Jen Shinefeld, a field epidemiologist with the city health department. She uses the term dope to denote drugs that are sold as heroin or fentanyl — “because you can’t go out and buy a bag of [just] heroin or fentanyl anymore. We use dope to express the variability of that term,” she said.

Shinefeld had been familiar with the presence of xylazine in the city’s dope supply but was surprised by how prolific it became between 2020 and 2022. Sherman remembers some corners specifically marketing drugs as “tranq dope” before 2020; now, he said, tranq’s presence is simply a given.

“Philly used to be known for the purity of the heroin we had,” Shinefeld said. “Once heroin became less available, we became more of a fentanyl-based city — fentanyl has a shorter half-life. It’s a much quicker high. Tranq gives fentanyl longer legs, the longer-lasting high. That’s why it was initially added to fentanyl — to help mimic that traditional heroin high. But it doesn’t give you the happy hug that an opioid would give you. It causes people to black out, not remember things.”

Withdrawal from xylazine can be even more painful than getting off opioids, say doctors who work with patients seeking drug treatment.

“The brain receptor that xylazine works on is one of the same receptors we use to manage opiate withdrawal symptoms like elevated vital signs, severe hypertension, and [high heart rates],” said Christopher Martin, a Jefferson University Hospital psychiatrist who works with patients with psychiatric conditions and substance use disorders.

“It looks like a worse version of opioid withdrawal that tends not to respond to standard opioid withdrawal management. We know really well how to manage opiate withdrawal, but there is no FDA-approved treatment for any xylazine withdrawal that may go along with that.”

The unique pain of that withdrawal is causing many patients to leave Martin’s care before they’re ready, seeking the tranq they know can stop their symptoms. It’s causing others to avoid treatment entirely.

And withdrawal can come on quickly.

“If I do one bag [of dope], I’ll be well for an hour, if that,” said Will Jefferson, 37, who’s been homeless in Kensington for three years. He and Sherman used to sleep next to each other in McPherson Square Park. Another of Sherman’s friends, who gave his name as Chuck, said he didn’t seek out xylazine but believes its presence in the dope he buys has allowed him to self-medicate his severe anxiety. And his fear of withdrawing from it, he said, has kept him out of treatment.

In his last trip to a hospital seeking help, he lasted 4½ days before the withdrawal became too much, he said.

Sarah Laurel Lacerra, the founder of Savage Sisters, said her clients “want desperately to get sober, but they don’t want to be incredibly uncomfortable for a week. The recidivism rates in facilities are insane because of this lack of care for tranq detox.”

Serious wounds are slow to heal

It’s unclear exactly what causes the serious wounds that show up on xylazine users; it’s possible that its effect on the vascular system makes wounds quicker to open and slower to heal. Research on xylazine — which, after all, was never meant for human use — isn’t extensive, which makes harm-reduction measures for xylazine users harder to find.

“There’s some reason to believe that some of the rapid changes in the vasculature from a medicine that has pretty significant effects on blood pressure may cause some changes in blood flow” that can make it harder for wounds to heal, said Martin. “There’s some evidence that the substance itself can generate free radicals [unstable atoms that can damage cells], which can be damaging to tissue. The data is still dragging behind a bit.”

But the side effects of xylazine use are accelerating.

“To give you an idea, it was unusual, when I was in training between 2009 and 2014, to have a patient who had an amputation related to an opioid use disorder [in my care],” said Martin. “Now, I can’t recall the last time we didn’t have at least one person on our service who was in danger of losing a limb, or had already lost one or more.”

For drug users like Jefferson and Chuck, the prospect of tranq-induced wounds is terrifying and, they worry, increasingly inescapable. Jefferson so far has managed to avoid skin lesions but contracted endocarditis, an infection of the inner lining of the heart, shortly after he began noticing tranq in his drugs a few years ago. Chuck, 32, who’s originally from Levittown, talked last summer about developing a cluster of lesions on his torso that quickly grew infected.

They try their best to stay safe. But saying safe, Chuck said, can mean simply assuming that whatever he buys is tainted — there are no test strips for xylazine as there are for fentanyl. Jefferson asks more experienced drug users for advice, but they’re dealing with the same tainted drug supply he is.

The rise of xylazine, like the rise of fentanyl before it, has renewed calls for a safe drug supply — a concept that’s being explored in successful heroin prescription programs in Canada and Europe. But for those working with drug users in Philadelphia, that seems almost insurmountable.

“Do I think a safe supply is necessary? One hundred percent,” said Lacerra. “Do I think it’s realistic? No. We’re miles away from that — there’s so much opposition to a safe consumption site, let alone safe supply. We’re at the point where we’re doing crisis intervention.”