A warning about life-threatening bleeding linked to use of synthetic cannabinoids -- commonly known as fake weed or spice -- was issued by the US Centers for Disease Control and Prevention on Thursday after two deaths and dozens of patients appearing in ERs with serious unexplained bleeding.
A total of 94 people -- 89 in Illinois, two in Indiana and one each in Maryland, Missouri and Wisconsin -- were seen in emergency departments with heavy bleeding between March 10 and April 5, according to the CDC outbreak alert.
Both of the fatalities occurred in Illinois. Interviews with 63 of the Illinois patients revealed that all had used synthetic cannabinoids.
Synthetic cannabinoids are mind-altering chemicals that are made in a lab and sold either sprayed on shredded plant material so it can be smoked like marijuana or as liquid that can be vaporized in e-cigarettes. "Fake weed" products are marketed in shiny packages with hundreds of brand names, including Spice, K2, Joker, Black Mamba, Kush and Kronic.
At least three product samples in the latest outbreak tested positive for brodifacoum -- rat poison -- and further laboratory tests confirmed this exposure in at least 18 of the Illinois patients.
"A working hypothesis is the synthetic cannabinoids were contaminated with brodifacoum," according to the CDC.
"This is the first time bleeding has ever been associated with synthetic cannabinioids," said Professor Paul L. Prather of the Department of Pharmacology and Toxicology at the University of Arkansas' College of Medicine, who was not involved in the CDC report. "It is certainly possible that the bleeding issues ... might be due to products laced with the rat poison brodifacoum."
However, he suggests that these adverse effects might be caused by an as-yet-unidentified synthetic cannabinoid chemical.
Specifically, this newest synthetic cannabinoid chemical could be derived from coumarin, a special class of chemical compounds, he believes.
A latecomer among synthetic cannabinoids, coumarin derivatives were first identified in a 2012 Journal of Medicinal Chemistry paper. This class of chemicals activates the cannabinoid receptors in the brain while acting as anticoagulants or blood thinners. Warfarin and phenprocoumon, blood clot-preventing drugs prescribed to heart patients to protect them from getting heart attacks, are coumarin derivatives.
Although bleeding, seen for the first time in Illinois, is a "whole other can of worms," Prather said, "there's a huge number of toxic effects of synthetic cannabinoids."
"They produce a lot of neurological side effects. Seizures actually bring people into emergency departments a lot of the time," he said. Other important neurological side effects include psychosis, panic attacks, agitation, confusion and catatonia.
"Young patients will come in with acute renal or kidney failure," he said. There are also troubling effects on the heart (chest pain and hypertension) and, recently, gastrointestinal problems and hyperemesis syndrome: an extreme amount of vomiting.
"What happens with the synthetic cannabinoid clandestine laboratories is, they're very smart people, and they look at these papers and they go, 'Oh, this compound has been developed, and it binds to these [cannabinoid] receptors, so if I produce this in my lab, I can probably sell this, because when people take it, it will probably produce euphoria like marijuana does,' " Prather explained.
Yet, he said, the compounds the clandestine scientists create -- even when the formulas come from a published scientific paper -- are "totally unknown chemicals." Plus, there's a lack of quality control.
"These drugs are made in a clandestine lab. Who knows what kind of contaminants are in this laboratory, and who knows from batch to batch how much of the chemical is actually made" -- or the concentration of each chemical made, Prather added. One synthetic weed product might be four specific chemicals of a weak concentration, but the next time you buy the same product, it might be five chemicals of high concentration.
"If you've ever been to a drug company, they have the most rigid quality control you can imagine," Prather said. Plus, there's a lot of testing to ensure safety. "Believe me, in the drug industry, you kill a lot of rats and you kill a lot of mice before you get to the point of that final drug."
Drug users are "the guinea pigs and the rats and the mice for the development of these compounds," Prather said. "It's really kind of crazy."
At the National Institute on Drug Abuse, Dr. Ruben Baler, a health scientist administrator, is getting the word out about the dangers of synthetic cannabinoids by speaking at conferences, giving lectures across the nation and talking with reporters.
He believes that "the perception of harm is going up and usage is going down, at least among teenagers."
In fact, American Association of Poison Control Centers data indicates a decreasing number of exposures to synthetic cannabinoids reported between 2011 and 2017. Poison control centers across the country received 6,968 calls about these drugs in 2011, compared with 1,952 in 2017. As of March 31, there have been 462 reports this year.
"I don't see an explosion of use among young people," Baler said. Mostly, those who gravitate toward synthetic cannabinoids are "marginalized people," including the homeless and those affected by mental illness, he said. "That's where you see the deaths so far."
Enforcement of the law is not the role played by the National Institute on Drug Abuse; that role is played by the Drug Enforcement Administration, whose spokesman, Rusty Payne, says synthetic cannabinoids are designed for one reason only: "to get your credit card, get you high and addicted, and keep you coming back for more."
The DEA first encountered synthetic cannabinoids about 2006, Payne said.
In 2012, the US government passed the Synthetic Drug Abuse Prevention Act, which classified a number of "designer drugs," including synthetic cannabinoids and synthetic hallucinogens, under Schedule I of the Controlled Substances Act -- meaning they have no accepted medical use and high potential for abuse.
Synthetic cannabinoids are made mainly in labs in China and mostly distributed online or at gas station convenience stores. "It used to be open shelf, but now this stuff is in the back," Payne said.
"Ten-plus years of these problems," he said. Despite the constantly changing chemical formulas, synthetic cannabinoids are considered illegal. Still, "that doesn't mean it's easy to prosecute," he said.
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"Terrorists are increasingly turning to drug trafficking to finance their operations," Payne, said, adding that the DEA has seen "significant amount of money transfers" into the Middle East of late, including Lebanon, Jordan, Syria and areas of unrest that are "financial system black holes." Cash from synthetic cannabinoids, in particular, is flowing to these nations.
Drug users who turn to synthetic cannabinoids are playing Russian roulette, Payne said. They are dangerous and even life-threatening, as the CDC reports. His thoughts are echoed by Baler and Prather, who added, "You hope you're getting euphoria, but who knows what else you're going to get?"