To learn what had caused this "zombie outbreak," Roy Gerona, an assistant professor in the clinical toxicology and environmental biomonitoring laboratory at the University of California, San Francisco School of Medicine, needed samples. He immediately contacted the New York Police Department, emergency services and various city hospitals, but no one spent more than a New York minute turning him down.
After he made a crucial call to a friend in the Drug Enforcement Administration, a shiny package found at the scene and labeled "AK-47 24 Karat Gold," along with blood and urine samples from eight patients, promptly arrived in the UCSF lab.
Gerona and his colleagues set to work analyzing these samples.
A new analogue
Separating a portion of herbs contained in the package, Gerona and his colleagues used mass spectrometry to identify them.
"You really don't know what to look for," he explained, so any of the typically used drug-testing panels are not helpful.
Gerona and his co-researchers discovered that the package contained the synthetic cannabinoid known as AMB-FUBINACA, an analogue of AB-FUBINACA, which was developed as a potential pain medication by Pfizer in 2009.
Three years later, Japanese authorities identified AB-FUBINACA as a potent illicit drug, and by January 2014, the United States had designated it a Schedule I controlled substance, explained Gerona.
Within months, an analogue, AMB-FUBINACA, appeared on the streets in Louisiana as the psychoactive ingredient within a product called "Train Wreck 2." By July 3, 2014, the State of Louisiana prohibited it by an immediate emergency rule.
Most of these drugs are distributed as mixtures of herbs, spices or shredded plant material sprayed or laced with various chemicals similar to THC, the psychoactive ingredient in marijuana. Synthetic cannabinoid products are referred to by many names, including K2 and spice.
To avoid regulation, the precise chemicals in the products are constantly changing, yet this means the medical consequences are unpredictable, according to the National Institute on Drug Abuse.
"Clandestine labs that are producing these really have a wide variety of choices, and they just move onto the next one that is not yet regulated," Gerona said.
Gerona and his co-authors say that "more than 540 new psychoactive substances" were reported to the United Nations Office on Drugs and Crime last year alone.
"My feeling is that what is reported and what is published is still an underestimation of the actual number," he said, adding that information on synthetic cannabinoids is usually classified in the US.
In their analysis, Gerona and his colleagues also discovered breakdown products of AMB-FUBINACA in the blood samples from the eight patients, who'd metabolized the product quickly, though they continued to feel its effects for hours.
One patient had a blank stare and was sweating, medical staff said, though his heart sounds were normal. His movements were slow and mechanical, and he had "intermittent periods of 'zombielike' groaning," wrote Gerona and his colleagues.
According to Gerona, one issue with synthetic cannabinoids is that there's such a wide variety of them, yet there's "no typical toxidrome," a catalogue of symptoms that form the basis for a diagnosis. When a patient appears in the emergency room, the assembled doctors have no idea what they're facing -- or where to look to find out.
"This one from New York was atypical," Gerona said. "Primarily for potent synthetic cannabinoids, you would typically have cardiotoxicity; you would have seizures; sometimes you would have acute kidney injury -- but this one did not have all that. It was just a severe depressant effect."
Similarly, Suzanne Bell, a forensic and analytical chemist at West Virginia University, has been looking at toxicity and byproducts of synthetic cannabinoids and "trying to understand these unusual effects. These are not what you see with marijuana, so something else is going on."
To deal with this difficulty, Gerona has started a psychoactive substance surveillance consortium of 10 medical centers with the aim of collecting biological samples and comprehensive clinical data from cases appearing in emergency rooms across the nation.
"Say we have 1,000 cases, then we can query that database and look at a new case and search for similar features," he said. He and his colleagues are hoping to define the signs and symptoms an ER doctor should look for to identify a synthetic cannabinoid.
"And maybe also by doing this, we can look at the treatment regimens to see which ones are effective and can potentially be used for a particular case," Gerona said.
This is all part of the "new paradigm" to responding to the challenge of many new designer drugs, he added.
"It is much more difficult to make the cannabinoids than methamphetamine and similar drugs like that," Bell explained. "The skill level is much higher. You have to be a skilled organic chemist to pull it off."
It's also not something that can be done in someone's basement. Fairly specialized apparatus the kind found in a pharmaceutical synthesis lab would be needed.
The clandestine labs that create synthetic cannabinoids "would be fairly sophisticated operations," Bell said.
According to Gerona, the scientists behind designer drugs are reading scientific journals and examining expired patents in search of formulas to create synthetic cannabinoids.
He's also concerned about the opioid analogues found on the black market. People who have become addicted to painkillers buy what they believe to be Oxycontin on the black market but instead purchase a more potent opioid such as fentanyl.
"We have been on a constant cat and mouse chase with the clandestine labs in China," Gerona said. "Really, the purpose of our paper is to bring attention also to policy-makers. There's a lot of issues embroiled into the designer drug space. This is a pressing problem that needs a solution."