Synthetic Marijuana: What Is It, And Is It Riskier Than Regular Pot?

Synthetic marijuana has been shown to get people good and high. But this is not your parents' weed.

Synthetic marijuana

DEA

Drug Week

Popular Science

Synthetic marijuana carries the sort of junior-circuit connotation befitting a drug high-schoolers favor — pot's answer to the wine cooler. Then you read stories like that of Emily Bauer, a Houston-area teenager who suffered series of strokes that left her blind and paralyzed after she smoked some fake weed she bought at a gas station.

Over a matter of weeks in December she went from having migraines to falling into a daylong psychotic episode, and in January emerged from a medically induced coma with profound brain damage. Her stepfather told CNN: "I'd never have thought we'd be in this situation. If she had bought it off the street or from a corner, that's one thing, but she bought it from convenience store."

Her ordeal and others like it sound like real-life Reefer Madness, made all the weirder by the shady legality of it all. But what is synthetic cannabis, and can it really be that much more dangerous than regular weed?

As sold, synthetic cannabis comes as little pouches with brand names such as K-2 or Spice, full of tea-like dried herbs treated with chemicals that contain cannabinoid molecules. A 2009 thematic paper by the European Monitoring Centre for Drugs and Drug Addiction lists three major categories of these compounds:

— The "classical cannabinoids," THC analogues based on a dibenzopyran ring, were developed in the 1960s. They include HU-210 (for "Hebrew University," where it was developed), and Nabilone and Dronabinol, which can be used to treat nausea after chemotherapy.

— The "non-classical cannabinoids," the cyclohexylphenol series developed by Pfizer in the 1970s. They include CP 59,540 and CP 47,497.

— The "JWH compounds," named for John W. Huffman of Clemson University, one of the scientists who created them in the 1990s. His and other labs developed them largely from organic compounds called indoles and pyrroles. Several of these molecules, too, have been shown to stimulate appetites and suppress nausea, for instance, and may have some benefits for sufferers of PTSD.

They've also been shown to get people good and high. Huffman, now an emeritus professor, has gone on record expressing resigned dismay that anyone would actually smoke the stuff. "These things are dangerous — anybody who uses them is playing Russian roulette," Huffman told the Los Angeles Times in 2011. "They have profound psychological effects. We never intended them for human consumption." (Weary of his notoriety, he declined to comment for this story.)

Spice

DEA

This spate of adverse events keeps any clinical trial from happening, because nobody wants to touch it.
Huffman wasn't surprised in 2009 when he first heard of people producing and selling synthetic cannabis. There are around 500 molecules in the family, and at least three of them are simple to produce: "You can make them in two steps from commonly available starting materials," he told the Times. He and other colleagues published a 2011 paper about synthetic cannabinoids entitled "Hijacking of Basic Research" that raised the specter of "another ecstasy-like problem" because "many hundreds of other compounds that could have cannabimimetic effects are not yet specifically regulated."

When the "spice" products first went on the market about nine years ago, they had certain advantages to pot, especially for young users: They weren't illegal, they were easy to get and they didn't turn up in drug tests. But of course they also hadn't been used enough for people to understand the potential risks. In 2010, more than 11,000 American emergency room visits were tied to synthetic cannabinoids (to be fair, regular pot generated nearly 40 times that many). European countries started cracking down. The Drug Enforcement Agency followed suit, listing as Schedule I controlled substances five of the compounds, which can be an order of magnitude more potent than THC, the cannabinoid in marijuana, depending on how they bind to the brain's cannabinoid receptors. Even now, as labels of the stuff explicitly state that they're not for human consumption (i.e., an incense), reporters have found clerks who recommend smoking it.

Dr. H. Westley Clark, the director of the Center for Substance Abuse Treatment, said that in determining which substances to regulate, the federal government tends to err on the side of personal freedom until thousands of people turn up in hospitals. In that regard, he said, 2010 was a tipping point for making synthetic marijuana a priority. That year the DEA moved to control five specific chemicals (including three JWHs) and various states began enacting their own bans, which are still spreading. Even now it doesn't seem too tough to find, though, when police are ballyhooing busts of drug dens with such nefarious names as Pleasant Avenue Wireless & Smoke Shop, Bonkerz and Sycamore Market.

Spice packaging

DEA

Marijuana carries a compound shown to dampen the schizophrenia-like effects of THC. Not so with the synthetics.
"If the early marking says 'Look, I've got this great drug, and it causes agitation, anxiety, nausea, vomiting, elevated blood pressure, seizures, hallucinations, paranoid behavior and makes you catatonic and nonresponsive' — what's the demand going to be?" Clark said. "With sufficient passage of time we discover all these other things. Now regulators need power."

Not only are the synthetics crazy strong, then, they also arrive in a vacuum. Multiple meta-studies of longitudinal studies have tied long-term marijuana use, especially from a young age, to increased incidence of chronic (no pun intended) psychosis. The risk remains "modest," according to this 2011 Current Psychiatry article on the connection between cannabinoids and psychosis. That may be in part because marijuana, at least, carries a compound called cannabidol shown to perhaps dampen the schizophrenia-like effects of THC. Not so with the synthetics. A U.K. survey last year found that 93 percent of people who had used both natural and synthetic marijuana preferred the old-fashioned plant, citing the harsh effects.

For the average user on the street, then, the effects of the synthetics are potentially nasty. Moreover, the precise chemicals and doses are unknown to users and responding physicians, said Dr. Joseph Pierre, the UCLA professor and schizophrenia expert who authored the Current Psychiatry article.

"They're marketed as 'herbal' products, and people tend to equate 'herbal' with 'safe,'" Pierre said. "We live in a society where we're not used to expecting these things are going to cause a lot of harm." But along with the approximate effects of pot come some of its lesser-known risks, including arrhythmia, heart attacks and seizures. And medical literature has recorded nasty psychological effects — hallucinations, disorganized thoughts, paranoid delusions — increasingly among users who had no history of vulnerability to mental illness. "Some of the patients are becoming pretty floridly psychotic," Pierre said. "The last time I counted, there were more than 50 of those cases in the medical literature." In several of those, he said, the effects lasted weeks or months.

They were never intended for human consumption.
The military has already banned all similar compounds. Pierre said that with some 500 compounds to consider, the federal government might eventually issue a similar blanket ban beyond the scant five the DEA has listed. New Zealand booted 50 synthetic cannabinoids off the market late last year.

Meanwhile, Clark is concerned that the potential benefits of the synthetic cannabinoids stand to suffer from the association with drug scares. "Now that we've got this spate of adverse events, it keeps any clinical trial from happening," he said, "because nobody wants to touch it."