Staying current with the content of drugs sold on Philadelphia streets is a bit like being in an "arms race," said Dr. Chris Martin, a Jefferson Health psychiatrist who treats patients hospitalized with problems tied to substance use.

As soon as he and his colleagues understand the symptoms of the latest adulterant in illicit drugs, a new chemical comes along, Martin said.

The health department's drug surveillance program recently detected the presence of sedative tranquilizers and synthetic opioids, including some stronger than fentanyl, which is about 50 times more potent than heroin. A statewide street-to-lab drug checking program has picked up the presence of a variety of other dangerous chemicals in the city's opioid supply.

"The illicit drug supply is as dangerous as it has ever been," a spokesperson for the city's health department said.

Helping break the cycle of addiction has always been difficult: "Your brain's hijacked, one, and two, you're physically addicted, dependent," said Stephanie Klipp, a harm reduction nurse in Philadelphia. "And then you have social determinants of health working against you like food disparity and housing disparities and trauma. What layer of the onion do you peel back first to try to get individuals help?" 

With the swiftly shifting and increasingly poly-chemical opioid market, health care providers and outreach workers on the front lines are confronting even steeper challenges as they treat people who have overdosed and others experiencing severe withdrawal symptoms or suffering from wounds related to drug use.

Christopher Moraff's nonprofit, PA Groundhogs, tests drugs using mass spectrometry technology in partnership with the Center for Forensic Science Research and Education in Willow Grove, Montgomery County. Data from this street-to-lab program informs the community about what is in the local drug supply, how it shifts over time and what new psychoactive substances may appear.

Dealers are selling bags of dope with smaller amounts of fentanyl and increasingly higher amounts of xylazine — a veterinary tranquilizer that can cause necrotic skin lesions and suppress breathing — partly due to recent arrests of the Sinaloa Cartel that have disrupted the fentanyl supply, Moraff said.

"There's a fentanyl drought right now because the price has gone up, and a lot of brokers have been cut out of the game," Moraff said. "There's obviously still fentanyl out there, but people are putting a lot less (in bags). ... They're conserving it."

In addition to xylazine and fentanyl, recent opioid samples obtained by PA Groundhogs and sent to CFSRE for analysis also contained benzodiazepine analogs, PCP and nitazenes, lab-produced opioids with no approved medical use that can be significantly more potent than fentanyl.

On May 13, the health department issued an alert that the alpha-2-agonist, medetomidine, had been detected in drug mixtures sold in the city and that a large cluster of people had reported to hospitals with symptoms such as bradycardia, hypotension, slowed breathing and extreme sedation — with unresponsiveness lasting as long as six hours in some cases. No one died from these drug-related illnesses, according to the health department. 

But Philadelphia's fatal drug overdose rates remain at record highs, with an estimated 1,300 unintentional drug overdose deaths in 2023 — the seventh straight year with more than 1,100 such deaths reported, according to a Pew Charitable Trusts report published in April.

Naloxone, sold under the brand name Narcan, can reverse opioid overdoses, but it doesn't work on xylazine, medetomidine or other chemicals popping up in the drug supply.

Because xylazine can slow breathing and lower heart rate and blood pressure to dangerous levels, a person who is overdosing needs rescue breathing in addition to Narcan, Klipp said.

When she was doing street medicine in Kensington, overdoses seemed to come in waves, Klipp said.

"There'd be a really bad batch of something, and then people would be overdosing everywhere, and then it would lift," Klipp said. 

Each time she revived someone, she said the person would immediately go into intense withdrawal.

"Honestly, I think it's traumatizing for everybody," Klipp said. "You're helping save someone's life, you make someone horrifically sick. … And then you think the person's probably going to have to get themselves out of withdrawal. … They're going to have to overcome all that naloxone that you gave them. And they're probably going to overdose again. It's just like, you can't stay with them."

Around the time the city issued the medetomidine alert, "we would reverse patients, or they were reversed in the field with naloxone, and then they came in with heart rates that were incredibly low, and that is something we've never seen before," said Dr. Lauren Murphy, an emergency medicine physician and toxicologist at Temple University Hospital. "This was completely new to us."

Many of those patients who seemed to have been exposed to medetomidine were admitted to the hospital, partly to monitor them until their heart rates returned to normal, Murphy said. But even if a "substance or a new contaminant or adulterant doesn't cause immediate death, it may cause other problems down the line. And so because (medetomidine is) so new, we still haven't seen what that's going to be." 

Another process that has become more challenging with the poly-chemical supply is withdrawal management, providers said. Trying to ease patients' withdrawal symptoms is not only humane but also helps people stabilize enough to decide if they want to transition to medication for opioid use disorder, such as methadone or buprenorphine, Klipp said. These drugs can help control cravings, allowing people to begin rebuilding their lives. 

But not knowing what people are taking – and often users don't even know what they're getting – makes finding medications to ease withdrawal for patients harder than it used to be.

Plus, the "patients are coming in sicker," Martin said. "The vital sign abnormalities that we see can be more dramatic. The severity of the physical symptoms that people have are more dramatic and often happen a little bit faster."

Adulterants mixed into the illicit drug supply is not completely new, however, Murphy said. In the 1980s, clusters of people who used a drug marketed as "synthetic heroin" that contained a contaminant developed irreversible, chronic Parkinson's-like symptoms. Levamisole, a medication used to treat parasites in veterinary medicine, appeared as a cocaine adulterant in the early 2000s, causing severe health conditions.

"There's always something dangerous in the substances that people are injecting," Murphy said. "It's not controlled. It's bulked. It's adulterated. There are always dangerous components."

But with more people addicted to potent opioids and unknown chemicals, treating pain in medical settings has become difficult, Murphy said.

"Ibuprofen, Aleve, Motrin … that stuff doesn't touch opioids," Murphy said. "That's why opioids were started in the first place. And that's really the last line. Once it no longer works, you don't really have anything else to break the pain."

If someone with opioid use disorder needs emergency surgery, for instance, and "their tolerance is very, very high – we're talking like superhuman tolerances to fentanyl and opioids – no matter what we give them, they're still in excruciating pain," Murphy said. "It's just really awful for those patients that that's a side effect of their substance use disorder."

What has also been challenging is often not being able to help people with substance use disorder at that golden moment in the hospital when they feel ready for addiction treatment, Murphy said.

"I have tons of patients who are interested in rehab, but we don't have enough rehabilitation centers, or they're not funded enough," Murphy said. "And it's having the supporting resources. It's not just being able to help the patient in the acute setting after an overdose, but it's being able to get them into recovery."

Martin said his colleagues' support helps him maintain morale. So does challenging perceptions of "success."

"Success might be convincing someone (that) today we're going to work on a plan to cut down on IV usage and shift to a safer way of using," Martin said. "Success might be preserving a limb and treating pain and building up rapport, knowing that there's a high likelihood that the patient is going to leave before they complete their treatment – but developing enough of the trust and rapport that has often been lacking in this space, that they actually come back in."