Anita Gupta first suspected that the Philadelphia heroin trade could be taking a deadlier turn months ago, when she saw overdose patients at Hahnemann University Hospital who didn't respond as they should have to the antidote drug emergency workers gave them.

"The symptoms were worse than we were used to seeing," said Gupta, an anesthesiologist, pharmacist, and pain specialist at Drexel University College of Medicine. "We were getting patients with symptoms of near-death, and often required multiple doses of the antidote naloxone."

Now she and other physicians think they may know what's to blame: A synthetic opioid called W-18 that law enforcement officials say may be circulating in Philadelphia. It's so powerful that it can cause death in microscopic doses, according to a recent Drug Enforcement Administration bulletin warning that the substance is said to increase the strength of heroin and cocaine.

"It put a name to what was already going on," Gupta said. "My suspicion is, W-18 is something we're already dealing with."

The opioid epidemic - whether doctor-prescribed painkillers, heroin, or both - is considered the worst drug crisis the United States has ever faced. About 78 people die each day from opioid overdose, according to the Centers for Disease Control and Prevention. A half-million have died from opioids since 2000.

Naloxone, marketed as Narcan, frequently brings drug users back from the brink of a fatal overdose.

But W-18, along with a handful of other synthetic opioids that can be added to heroin without the user's knowledge, may be too strong for naloxone to reverse. And, local physicians say, it's even throwing off seasoned drug users.

"We're seeing more unexpected overdoses in patients who were chronic, stable users, suggesting there's a contaminant in the heroin they were using," said Jeanmarie Perrone, director of medical toxicology at the Hospital of the University of Pennsylvania.

Most hospital laboratories are not equipped to spot W-18, Perrone said. Law enforcement officials say they haven't been able to prove that W-18 has killed anyone here.

"It scares the living crap out of us, but we haven't seen it yet," said Patrick Trainor, spokesman for the DEA's Philadelphia office.

But according to a police informant quoted in the DEA's unclassified bulletin, users were "dropping like flies" from W-18- tainted heroin. Drug dealers were giving naloxone to overdosing customers, according to the source. The DEA said it was not known whether the dealers were charging extra for saving their lives.

In internet forums, veteran opioid users warned against W-18. One commenter dismissed it as "not as pleasurable as heroin." Another cautioned that "the margin between high and death is incredibly small." A Reddit commenter compared W-18 to "chemical warfare" against users.

Though W-18 is often described as 10,000 times more potent than morphine, the claim is based on experiments with mice more than 30 years ago. It has never been officially tested on humans.

W-18, first synthesized more than 35 years ago, has been rising in visibility in recent months. In September, federal agents discovered more than 21/2 pounds of W-18 in the home of a Florida man implicated in an international fentanyl drug ring. (Fentanyl is a legal opioid, available by prescription, that sometimes is added to heroin to make it stronger.) In December, police seized nearly nine pounds of W-18 in a raid in western Canada.

W-18 is one of several so-called novel opioids, typically manufactured in China, that dealers purchase online. They're so novel that they are not yet restricted by the DEA and remain legal to possess in the United States.

These legal synthetics have caused "upwards of 50 deaths" nationwide during the last four months, according to Barry Logan, director of the Center of Forensic Science and Education. The center is the nonprofit research arm of NMS Labs, which tests for the substances at its Willow Grove headquarters.

NMS confirmed one death in Illinois caused by W-18 and is investigating its role in another.

"The bigger problem right now is the designer opioid U-47700 and the designer fentanyl, furanyl, fentanyl," Logan said, adding that NMS had detected the two substances in a string of fatal overdoses that reached from Florida to Maine.

Philadelphia doctors are braced for more overdoses, with or without the novel opioids.

"With so many people dying already, we don't need this," said Ted Christopher, chair of the department of emergency medicine at Jefferson Health. "The opioid epidemic is already a catastrophe, and this raises the ante."