A study published July 17 in Drug and Alcohol Dependence found that almost three-quarters of patients in treatment for substance use disorders (SUDs) report using synthetic cannabinoids to avoid having marijuana detected by drug tests. The study, by Erin E. Bonar and colleagues, found that 38 percent of the 396 patients surveyed reported using synthetic cannabinoids, with 71 percent saying the reason was to get high without having a positive drug test. The most common reasons were curiosity (91 percent), getting high (89 percent) and relaxation (71 percent). Patients who used synthetic cannabinoids had higher rates of other substance use and higher measures of depression and psychiatric distress than other patients in the program.

“People do use these compounds primarily to evade drug tests,” said Kevin G. Shanks, a forensic toxicologist at AIT Laboratories in Indianapolis, who conducts many tests on biological samples — usually postmortem — for evidence of synthetic cannabinoids. “The typical urine drug test for cannabinoids does not pick up synthetic cannabinoids,” he told ADAW. This wasn’t known until about two years ago, he added. Now, however, people do know. So labs have to be updated to test for more than metabolites of tetrahydrocannabinol (THC), the active ingredient in marijuana, which doesn’t exist in synthetic cannabinoids.

Not marijuana

References to synthetic cannabinoids as “synthetic marijuana” or “synthetic weed” are misnomers, said Shanks. “These compounds are truly cannabinoids because they act on the cannabinoid receptors,” he said, “but they are nothing like THC in their effects on the body.” Also, if people think they are like marijuana, they could be dead wrong. There are many cases of death caused by use of synthetic cannabinoids, said Shanks.

Synthetic cannabinoids are full agonists, which means they produce more exaggerated effects than THC, said Shanks. “There’s much more agitation, much more tachycardia,” he said. THC is a partial agonist, with less severe effects.

No quality control

Many synthetic cannabinoid compounds were developed in legitimate research, with the process published and eventually forgotten about, said Shanks. These are in a gray area that he calls “trolling the patent” — clandestine chemists see that these compounds exist but are not scheduled (controlled by the Drug Enforcement Administration), or if scheduled, they can be modified in ways that aren’t scheduled. They then sell them as synthetic cannabinoids, which can have many “analogues” or chemically similar substances. These substances first appeared as “K2” and “Spice,” but there are constantly and apparently infinitely expanding types now out there, and there is no quality control regardless of what the compound is sold as.

“We have a long history with marijuana and THC,” said Shanks. “We know more about them every day from research.” By contrast, very little is known about synthetic cannabinoids, because there are so many different versions. “For 99.9 percent of the compounds showing up, we don’t have any toxicology or pharmacology information,” said Shanks. “They have not been through through controlled dosing studies, or clinical trials,” he said. “They may have been invented by someone in a lab, and we don’t even know if they truly act on the cb1 and cb2 receptors,” he said, referring to the cannabinoid receptors in the brain. “Even though people talk about K2 and Spice, we don’t know what they are — if someone buys them in a smoke shop or a head shop, you’re not guaranteed to have anything specific.”

Some products have as many as 11 different synthetic cannabinoids in them, said Shanks. “And we’ve seen some that sold as synthetic cannabinoids that didn’t have any,” he said.

Underground chemists

Most recently, Shanks and colleagues published a paper in the Journal of Analytical Toxicology that documented four deaths in Iowa and Nebraska, all centered around one specific compound: 5F-PB-22.

Shanks isn’t sure that controlling each individual substance is going to be effective, because then the clandestine chemists just move on to a different substance. The analogue law — and state analogue laws — can be useful, however. That way authorities can shut down head shops found selling such substances.

“I do think legislation is good, but it’s a double-edged sword,” said Shanks. “Legislating is almost a knee-jerk reaction, because it allows a lot of the underground chemists to use even more unproven and unknown compounds,” he said. “It’s a diverse chemical grab bag, with many of the compounds now out there having never been under patent, never studied,” he said. “There are outbreaks and illnesses that have been caused by synthetic compounds. Now it’s must mix and match, and we’ve gone from the ones we knew most about causing the problems to substances we know nothing about.”

“Clearly, further investigation is required with respect to the pharmacokinetics of 5F-PB-22 and other synthetic cannabinoids, their role in human toxidromes and their relevance to detection in postmortem casework,” Shanks and colleagues concluded in the Journal of Analytical Toxicology paper, which will be published next month. “Important point sources for this information will continue to include the US National Network of Poison Information Centers, reporting emergency departments and urgent care centers and medical examiner/coroner systems with their attendant toxicology laboratories.”

Bottom Line…

Sold under various names in head shops and smoke shops, synthetic cannabinoids are not marijuana and are killing people — including those who take them to evade drug tests.