When researchers at the University of Maryland School of Medicine and the Center for Substance Abuse Research (CESAR) set up a study in two Maryland emergency departments designed to identify overdose patients with synthetic cannabinoids in their system, they expected to find just that. Instead, out of 175 urine samples, only one tested positive.
“My initial focus was trying to figure out what synthetic cannabinoids people are using, and how they’re shifting with time, to link particular synthetic cannabinoids to a clinical presentation,” said Zachary D.W. Dezman, MD, MS, assistant professor of emergency medicine at the University of Maryland School of Medicine in Baltimore. “The reality was much more complex than what I had imagined.”
For the last 5 years, the U.S. drug trade, especially in the designer drug field, has moved faster than testing can evolve. This is especially true for synthetic cannabinoids, sometimes known as Spice or K2. These drugs are cheap to make and can be cut into other illegal drugs such as opioids, leading to mass poisoning events like those that occurred in Philadelphia and New Haven, Connecticut, in the summer of 2018, when double the usual number of overdoses showed up in local emergency departments.
In these cases, clinical laboratory professionals worked closely with emergency medicine physicians and public health agencies to identify what caused the spike in overdoses, and they can be a blueprint in how to work together in the future.
The Undetectable Problem
In the University of Maryland study, published in July 2018 by the Office of National Drug Control Policy, researchers discovered several things about patients’ drug use: that the most common individual drug detected was marijuana, and that some patients tested positive for as many as six substances. They also found striking differences in drug usage patterns in hospitals less than 40 miles apart. Two-thirds of samples in a Baltimore hospital tested positive for fentanyl, while nearly half in nearby Cheverly, Maryland, contained PCP.
But finding that so few tested positive for a synthetic cannabinoid was most surprising, said Dezman. A year later, after the laboratory had expanded its testing panel from 26 to 46 synthetic cannabinoid metabolites, still only one quarter tested positive. “It illustrates the difficulty of this problem,” he said.
Synthetic cannabinoids originally gained traction as substances that users could take “because they were able to avoid drug testing. The cannabinoids are different enough that a [tetrahydrocannabinol] screen will not detect them,” said Roy Gerona, PhD, an assistant professor at the University of California San Francisco, where he runs the Clinical Toxicology and Environmental Biomonitoring Laboratory.
About 3 years ago, opioid analogs like fentanyl started becoming popular, Gerona said. This was in part because tightening of opioid prescription medications sent drug users to the black market for drugs. At the same time, synthetic cannabinoids become even more accessible as their price dropped lower than that of regular marijuana.
The cheaper prices of synthetic cannabinoids have also led to their expanded use within the homeless population, Gerona noted. They most likely already had health problems that could make the effects of synthetic cannabinoids worse, and also make it more likely for them to seek emergency department treatment.
Working Together to Identify the Unknown
The typical pattern of drug use and detection is that a new analogue shows up, a new test is developed and validated, and by that time the drug market has moved onto something else. “It’s a cat and mouse game,” said Barry K. Logan, PhD, F-ABFT, senior vice president of forensic science initiatives and chief scientist at NMS Labs in Willow Grove, Pennsylvania.
And while testing via high-resolution mass spectrometry (MS) is the best technology to detect these substances, it’s not realistic for most laboratories. “Not every single hospital in the United States would have a high-resolution mass spectrometer or, the more difficult thing, to have somebody with an expertise who would be able to operate it and know how to interpret the results,” Gerona commented.
The way the federal government schedules drugs has helped to slow down the evolution of synthetic drugs. Instead of scheduling drugs one by one, the U.S. Drug Enforcement Administration (DEA) now identifies substances by core structure. That means that, even if a substance’s make up were to be tweaked, it still would be scheduled as illegal. Since that change, fewer new analogues are showing up, said Logan.
Another factor in slowing the evolution of drugs of abuse is that some labs, like NMS Labs, are looking at the overall picture versus only what arrives at emergency departments—or what is not showing up in testing.
For example, NMS Labs has a designer drug strategy team whose “job it is to monitor the landscape of new drug use in the United States,” Logan said. To get a top-level view of drug abuse patterns, this team monitors about 10 different categories of information, using data from sources like government reports, federal agencies, databases of MS data, medical examiner reports, medical literature, and conference proceedings.
The group also keeps tabs on trends internationally. The U.S. and China, for example, are now doing a better job in sharing information, and “when China started scheduling some of the opioid fentanyl analogues in the middle of last year, we saw those substances starting to disappear in the U.S.,” Logan noted.
Researchers also monitor drug user forums and drug user chat rooms to see what substances are being discussed. They even go into the field and talk directly to drug users, going so far as to collect samples from individuals at events like music festivals. “You can’t just sit and wait to figure out what the next challenge is going to be,” Logan said. “You’re going to be a lot more effective if you’re proactive and try to find these things yourself.”
Working Together in the Real World
While such a broad view of drug abuse is extremely useful, the healthcare community needs more real-time information about what is causing overdoses right now. This is where clinicians and clinical laboratorians working together can make significant inroads.
“We started reaching out to emergency physician and [emergency medical service] organizations, as well as professionals who work in poison control centers, to get more information and potentially do more testing of what we would call non-fatally intoxicated patients,” Logan said—individuals who overdose but don’t die. “We’re encouraging [these groups] to try to do more laboratory testing of emergency patients.”
This kind of cooperation helped clinical laboratory experts and emergency department clinicians identify the synthetic cannabinoid, SF-ADB, present in heroin over the summer. That event sent 165 people to the hospital in Philadelphia over a 2-day period in July, and resulted in 95 overdoses in 2 days in New Haven, Connecticut, 1 month later. Patients were treated with Narcan, but instead of helping, it turned them “very combative and agitated,” Logan said. “They were hallucinating, and the clinicians didn’t really know what to make of it.”
In Philadelphia, NMS Labs partnered with local poison control centers and with public health agencies to rapidly get samples from these patients and identify the drugs. Logan emphasized that clinicians and public health officials will never know the cause of outbreaks without close work with clinical laboratories.
Without clinical labs, “you lose the opportunity to inform drug users, as well as educate [emergency medical technicians] and emergency department personnel about the symptomology and how to successfully treat it,” Logan stressed. “We can use the identification of the substance to more quickly move it forward with [DEA] scheduling if that’s required. At the very least scheduling will be disruptive of the illicit trade and distribution of the drug.”
Just being aware of the “huge potential for false negatives” can make a difference in figuring out what’s really happening with a patient, Gerona emphasized. “Being vigilant on what the limitations of the assays are, and what they actually are used for, also helps a lot to maintain the integrity of the assay and make it more responsive to our patients.”
Gerona also thinks that clinicians, laboratorians, and test developers can better work together to “help broaden the breadth” of the assay, Gerona said. “We can lend our expertise to vendors. I think that will help the field, too.”
Jen A. Miller is a freelance journalist who lives in Audubon, New Jersey. @byJenAMiller