The young woman had pale skin and fire-red hair, and by all appearances was only minutes away from dying from opioid overdose.

The grim scene unfolded in February, in the Kensington section of North Philadelphia. It’s where the death rate from heroin mixed with illicit fentanyl ranks among the highest in the nation, and the sight of young bodies lying prone and unresponsive on the sidewalk has become the new normal for a cluster of impoverished neighborhoods that have already suffered decades of collateral damage from the war on drugs.

But in spite of the fresh needle marks on the young woman’s arms, it wasn’t a strong new batch of fentanyl-laced dope that sent her plummeting to the pavement near a makeshift campsite of homeless IV drug users.

Instead, witnesses said the woman was having a bad reaction to “Tookie,” a local street name for K2—a generic term used to describe one of hundreds of synthetic drugs designed to mimic the properties of the chemical in marijuana that makes people high, THC.

Unlike its organic cousin, however, synthetic cannabinoids can cause a range of adverse side effects, including seizures, psychosis, and cardiac arrest. Thousands of people have been hospitalized over the past decade after smoking synthetic cannabinoids, and dozens of fatalities have been attributed to the drugs, often when they are taken in combination with other substances.

The young woman with red hair was lucky; after 10 minutes in a catatonic state she came to, struggled to her feet, and by the time paramedics arrived, had disappeared back into the faceless mass of desperation that illicit fentanyl has left in its wake in communities across the U.S.

‘They live on a ventilator’

In recent months, The Daily Beast has documented a remarkable increase in the use of synthetic cannabinoids among IV drug users, a demographic that has traditionally shied away from substances with psychedelic properties. In Philadelphia, many opioid addicts have added hits of K2 to their daily cocktail of heroin and cocaine (the two most common drugs of choice among injection drug users).

“It’s like, everyone is smoking it now, I ain’t seen nothing like this before,” said Nancy Vasquez, a 34-year-old homeless drug user who has been injecting heroin and cocaine daily for more than a decade. “I don’t like [Tookie]. But I swear some people are actually smoking it instead of doing dope.”

Staff at Episcopal Hospital—just a short walk from the scene of February’s overdose—said two to three people a day on average now present with symptoms indicative of K2 intoxication.

“We see a lot of K2 overdoses,” said Joann Conti, a paramedic with the Philadelphia Fire Department. “This is really fucking nasty stuff. I mean when we come upon an overdose we just don’t know what’s in it. Sometimes they’re extremely agitated. And there’s no antidote. So all we can do is restrain them and take them to the emergency room. I’ve intubated people after smoking this stuff who never get extubated. They live on a ventilator.”

Sources in the harm-reduction community in New York City have reported seeing a similar rise in K2 use, especially in Brooklyn and the South Bronx—where fentanyl-laced heroin kills more New Yorkers per capita each year than any other area.

“The high is similar to dope and you can get more of it for cheaper and use all day out of one bag,” said Hector Mata, care coordination manager at Vocal-NY, a syringe exchange program in Brooklyn.

Mata says that much like benzodiazepines like Xanax, synthetic cannabinoids taken with opioids can also produce the “nod” effect many heroin users seek.

Though still referenced under the early brand names K2 and “Spice,” there are now at least 700 possible variations of synthetic cannabinoids that target one or both of the human brain’s primary cannabinoid receptors. Over the past year alone law enforcement officials have identified 70-80 different strains in seized drug samples.

Unlike THC, which is a partial agonist of the brain’s cannabinoid receptors, synthetic copycats are full agonists, meaning they completely saturate the receptors. Some researchers now speculate that newer versions of the compounds are targeting other, unknown areas of the brain as well.

“Some of the cardiac effects that are being noticed seem to be through serotonin receptors and other things, but that’s very sketchily known right now,” said Michael Gatch, a professor of biomedical sciences at the University of North Texas, during a hearing last year before the U.S. Sentencing Commission.

“We are now in our eighth generation of synthetic cannabinoids and they just keep getting more powerful and unpredictable,” said David Leff, a forensic narcotics expert who has spent decades studying the evolution of synthetic drugs. “Users you have no idea what you’re actually consuming. These are substances that have never been tested on humans.”

In fact, so little is known about synthetic cannabinoids that in April, Baltimore’s health commissioner compared smoking K2 to playing “Russian Roulette.”

Much like fentanyl-laced drugs, a single package of poorly mixed K2 can contain “hotspots,” or pockets of extremely high doses of one or more chemical compounds.

“Sometimes, you know, I take one hit and it’s just mild, and other times one hit knocks me on my ass,” said Patrick, a homeless IV heroin user who’s been smoking “Tookie” daily for about nine months.

Patrick spoke lucidly about his drug use for about 20 minutes, saying he liked the high from K2.

“I don’t know, this may sound weird but it makes me more creative,” he said. “And it mixes well with dope.”

A week later, when The Daily Beast encountered him a second time, he was slumped over a wooden fence in an abandoned lot, in a state of semiconscious, unable to respond to questions or lift his arm to accept a bottle of water he was offered.

“ Sometimes, you know, I take one hit and it’s just mild, and other times one hit knocks me on my ass. ” — Patrick, an IV drug user

Over a span of just a few hours on a recent afternoon, The Daily Beast encountered several people experiencing severe states of synthetic cannabinoid intoxication around Kensington’s teeming drug user encampments.

One man, who said his name was Juan, was able to maintain focus just long enough to confirm he had recently smoked the drug. But he quickly became distracted by hallucinations, shouting obscenities in the direction of a brick wall. The hypodermic needle he’d just used to shoot heroin was still dangling from his arm.

A woman encountered later in the day just steps away from where the young redheaded woman had overdosed months earlier was unable to stand on her own, and became confused and agitated when a reporter offered to help.

The side effects are consistent with reports from medical professionals.

“We generally see two types of reactions when patients present. There’s the somnolent, unresponsive patients who have trouble even moving, and then others react by becoming agitated or even aggressive,” said Dr. Edward Fishkin, chief medical officer of Brooklyn’s Woodhull Medical and Mental Health Center where dozens of people were treated over a period of two days in late May after smoking an as yet unidentified synthetic cannabinoid.

Fishkin said all the patients he treated during the outbreak were released after being stabilized. But he added that a lack of standardized diagnostic criteria for identifying an overdose of synthetic cannabinoids—or even a way to determine what substance a patient ingested—greatly limits treatment options.

“All we can really do is treat their symptoms and release them,” he said. “Very little is known about these substances, so we have no idea what they ingested or what the long-term consequences could be.”

An explosion a decade in the making

Synthetic cannabinoids landed on law enforcement’s radar in 2009, when a compound known as JWH-018 began turning up in brightly colored packaging for sale in U.S. smoke shops and convenience stores where they were marketed as “legal highs.”

In 2011 and 2012, faced with a spike in emergency room visits, the Drug Enforcement Administration banned a handful of the compounds. Chemists continued tweaking the drugs to skirt ever-evolving synthetic drug laws, but since peaking in 2015, calls to poison centers for synthetic marijuana dropped by more than half. But over the past year K2 has made a comeback; and a recent spate of poisonings has public health officials worried.

Since March, hundreds of people have been sickened in nine states due to a batch of fake weed contaminated with an anticoagulant found in rat poison. At least four people have died, and in Illinois authorities filed the first documented Drug-Induced Homicide charge against a defendant accused of providing a fatal dose of fake weed.

Theories abound as to why synthetic cannabinoids are making such a strong comeback among IV drug users. For years the compounds were a niche product, used primarily by research chemical (RC) enthusiasts; high school students who believed the drug was a safe alternative to marijuana; and people on probation or parole looking for a way to get high and still pass their drug tests.

Some say the renewed interest may be because, in low doses, synthetic cannabinoids can have a potentiating effect on opioids, including drugs used for medication-assisted treatment.

“Anecdotally I’ve heard there can be a dissociative experience that can help with anxiety, especially for those on medication-assisted treatment whose doctors refuse treatment if positive for benzodiazepines,” said Gus Grannan, a harm-reduction advocate in Philadelphia.

Others suspect the K2 itself may be mixed with fentanyl; however three samples of the drug recently obtained by The Daily Beast tested negative for the illicit opioid.

Like many fentanyl analogues trafficked in the U.S., synthetic cannabinoids are primarily synthesized in China, and there is evidence of a connection between the appearance of new fentanyl structures and new strains of synthetic weed.

From 2012-2015 there were nearly 2,000 clandestine drug labs identified in China, according to data from the United Nations. Some produce a variety of new synthetic drugs (PDF).

“ Very little is known about these substances, so we have no idea what they ingested or what the long-term consequences could be. ” — Dr. Edwin Fishkin

Last year federal authorities made international headlines when they announced the indictments of two Chinese nationals for supplying large quantities of fentanyl analogs to the U.S. market that were manufactured at two chemical plants in China. But what didn’t make the news is that the fentanyl sales were little more than a sideshow to a massive international drug empire that trafficked in multiple synthetic cannabinoids, including one, AM2201, that has reportedly caused seizures from as little as a single hit (PDF).

Meanwhile, at least three separate street sources who provide information regularly to The Daily Beast confirmed last month that a substance with pharmacological properties similar to K2 has been turning up in retail level packages of heroin, in some cases without the knowledge even of the dealers.

One source, “Jay,” says he was reimbursed after complaining of the unpleasant effects. Another user, who goes by the name “Bill” and frequently provides information on new brands of heroin and fentanyl described receiving three samples just days ago from a heroin dealer who seemed unsure of what he’d purchased. “He wanted me to tell him how it was, I told him, ‘look I’ll be honest, I’m lit, but it didn’t even get me well,” he said.

The Daily Beast obtained samples of one batch of the suspected adulterated heroin, but at press time was still awaiting lab results.

A spokesperson for Philadelphia’s Medical Examiner’s Office told The Daily Beast there have been no reported fatalities attributed solely to synthetic cannabinoids in the city. But the addition of another powerful and unpredictable drug into the mix among a population already facing crisis levels of homelessness and addiction has troubling implications.

Dr. Jahan Marcu, Senior Scientist at Americans for Safe Access, a marijuana advocacy group, calls the reemergence of synthetic cannabinoids a “product safety nightmare.”

“It’s like ordering a drink and not knowing if it’s 0 percent alcohol or full proof,” he said.

“We call these cannabinoids but that doesn’t mean they are—this is probably one of the most varied substances we’ve seen, we don’t know how these things metabolize in the body. So if smoking pot is like turning the amp up to six, using [synthetic cannabinoids] is like turning it to 10.”

As has become common practice, federal authorities have reacted to the rise in synthetic drugs through stricter enforcement and by enacting tougher penalties. In April the U.S. Sentencing Commission unanimously approved new guidelines for cases involving synthetic cannabinoids (PDF). As this article was going to press the DEA emergency scheduled another five synthetic cannabinoids.

More than 300 new synthetic drugs have “gone wild” over the past decade, and last year DEA identified a newly emerged novel psychoactive compound on average once every three weeks.

If the war on drugs has proved anything it’s that even black markets can innovate at a faster pace than laws can evolve.