Philadelphia health officials are sounding alarms about the emergence of new opioids in the city’s drug supply that are as much as 40 times more potent than fentanyl, the drug behind the city’s skyrocketing rates of overdose deaths.

Undetectable with traditional drug testing methods on the street, they are called nitazene analogues and are part of a class of drugs that can cause severe withdrawal symptoms and heighten the risk of overdoses, even among people who have been using opioids for years.

The new threat comes as opioid overdoses killed a record 1,276 people in the city last year. Those deaths were largely due to the spread of fentanyl, which is up to 50 times more potent than heroin and over the last decade has replaced heroin in the city’s drug markets. But nitazene analogues, in turn, can be as much as 40 times more potent than fentanyl. Both are synthetic opioids that can be produced in a lab.

Health officials first detected a nitazene analogue, N-desethyl isotonitazene, in December, in four separate samples sold on the street as “dope,” the department’s catch-all term for drugs advertised as powdered opioids. The department put out an alert about nitazenes last month.

“We want to get out ahead of this,” said Daniel Texeira daSilva, the medical director of Philadelphia’s Division of Substance Use Prevention and Harm Reduction.

Higher potency, greater overdose risk

People experiencing addiction who have used drugs containing nitazenes have reported serious withdrawals that come on faster than they’re used to.

And most buyers don’t realize what they are getting, creating a hazard similar to the situation with another newer additive that has roiled the drug scene — xylazine, or “tranq.”

This powerful animal tranquilizer, which is not an opioid, can cause serious skin lesions and severe withdrawal symptoms. A sedative, it elevates the risk of overdoses in people who use it in combination with opioids. Over the last two years, xylazine has contaminated much of the city’s dope supply, said Jen Shinefeld, a field epidemiologist with the city health department.

“People’s tolerances have changed. So if they’re using a bag of nitazene and then they get a regular tranq dope bag, it’s not [staving off withdrawal],” said Shinefeld. “And that happens for some users very quickly, within the course of a few days.”

Shinefeld and her colleagues monitor the drug supply by regularly submitting street samples of drugs to a local drug testing lab, Horsham’s Center for Forensic Science Research and Education (CFSRE).

But on the street, without that kind of sophisticated drug-checking technology, it’s difficult for users to determine exactly what they’re buying. For example, the fentanyl testing strips that many harm-reduction organizations hand out in the city do not detect nitazenes.

The health department’s recent alert noted that nationwide, about 1,000 to 2,000 fatal overdoses since 2019 were associated with nitazene analogues, but that number is likely higher because there isn’t widespread testing for these drugs.

Shinefeld is not aware of any fatal overdoses from nitazenes in the city, because the Medical Examiner’s Office doesn’t test for them, she said. The health department has warned that people overdosing on nitazene analogues may require several doses of naloxone, a drug used to treat opioid overdoses, before they are revived.

Nitazenes were first detected in Pennsylvania last fall, said Barry Logan, CFSRE’s executive director.

By then, they had already hit the Midwest, and other parts of the country. Taylor Wood, the lead technician and drug-checking program manager for Chicago Recovery Alliance, a harm-reduction organization in Chicago, said nitazenes were first found in the city’s drug supply in 2021.

Clients reported harsher withdrawal symptoms: “The phrase was ‘It makes you sicker quicker,’” Wood said.

After the advent of nitazenes in Chicago’s supply, Wood began to find higher percentages of fentanyl in drug samples, possibly because dealers were reacting to clients’ higher tolerance from exposure to nitazenes. That’s also dangerous for people who haven’t been exposed to nitazenes, who might overdose after taking higher doses of fentanyl than normal, Wood said.

Nitazenes are also causing overdoses in the Chicago area. Wood noted at least one fatality in which a person who was sold what was believed to have been heroin tested the sample for fentanyl. When the test came up negative, the person used the sample. But, instead of heroin, it contained a nitazene analogue.

Difficult to know how much you’re getting

Nitazenes materialized on the drug scene after federal regulators started trying to crack down on fentanyl, which exploded onto drug markets in the mid-2010s.

The federal government has banned some nitazene analogues, which have never been approved for human use. But others aren’t specifically mentioned in federal laws, including the substance that turned in up Philadelphia this winter.

Manufacturers of illicit drugs may see a new opportunity to find ways around the law, said Logan, of Horsham’s Center.

It takes a small amount of nitazene to produce a high — less than fentanyl and much less than heroin. That contributes to a “chocolate chip cookie effect,” he said, creating a potentially lethal variability between samples of dope, where some might have a significant amount of nitazenes and some might not have any at all.

“The other thing about having a drug that is more potent is that there’s a lot less of it you have to move around,” Logan said, citing a potential benefit for traffickers moving product through the country’s drug markets.

Philadelphia officials say they’re eager to educate the public about the presence of nitazenes in the drug supply before it becomes more widespread.

Once clients in Chicago learned they may have been using nitazenes, Wood said, they had more knowledge to keep themselves safe — and to understand their experiences.

“Some individuals might not understand what’s happening to them in that moment,” Wood said. “Putting the messaging out there is really important.”