Synthetic Marijuana Has Real Risks

Synthetic marijuana refers to a collection of compounds called synthetic cannabinoids, or SCs, that loosely resemble tetrahydrocannabinol (THC), the natural chemical primarily responsible for marijuana's characteristic high. (Read our new report, "Up in Smoke: Does Medical Marijuana Work?")

The compounds can be sprayed onto plant materials, which have no psychoactive properties of their own, and then smoked. But experts say that it's a mistake to equate the synthetic drug with the botanical. "[These compounds] have nothing to do with marijuana," says Robert Galli, M.D., a professor in the Department of Emergency Medicine at the University of Mississippi. "They are dangerous drugs that are really quite different."

The "highs" produced by SCs can be wildly unpredictable, and they've been associated with thousands of emergency-room visits for problems like delirium, confusion, agitation, and violent behavior, plus an alarming uptick in calls to poison-control centers.

That difference is rooted in how the chemicals behave in our bodies. The natural substance, THC, is a "partial agonist," meaning that it binds incompletely to brain cells. But synthetic cannabinoids are "full agonists." They bind completely to those same cells and can be 10 to 200 times stronger than the natural compound.

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The Drug Enforcement Agency began criminalizing SCs back in 2011. But rather than quell the market for "fake weed," that legislative maneuver touched off a deadly game of whack-a-mole. Chemists tweaked their existing formulas to create new compounds that were still technically legal. The DEA eventually criminalized those compounds as well, leading to more modifications from the chemists, and so on.

As this cycle has continued, the number of SCs on the market increased dramatically. In 2012, 51 new compounds were identified (compared to just two in 2009). That same year, Congress passed the Synthetic Drug Abuse Prevention Act, banning five different structural classes of synthetic cannabinoids. The idea was that banning entire classes of compounds as opposed to just individual chemicals might finally stop the flow of chemicals into unsuspecting communities.

But three years later, doctors like Galli found themselves confronting the worst adverse event outbreak to date. The culprit was MAB-CHMINACA (MABC), a new SC that has proven far more toxic than its predecessor, AB-CHMINANA (ABC). The DEA criminalized ABC in 2014, after it caused six deaths. Chemists then added a single methyl group to that compound to produce MABC, which has since caused 721 medical emergencies and nine deaths.

The psychological effects, like hallucinations and psychosis, have been more severe on MABC, says Galli. And so have heart-related problems. The number of calls to poison-control centers jumped from 2,700 per year to 7,800 per year between 2013 and 2015.

In 2015 a bill was reintroduced in the Senate that would enable prosecutors to pursue synthetic-marijuana dealers based on marketing and product-label claims.

But at $5 to $10 a gram, synthetic marijuana is just one-half to one-fourth the cost of real marijuana, so it remains popular. And while convenience store and smoke-shop owners generally no longer display the drugs, they may still be available behind the counter at many of those same stores. They're also easy to find online.

The belief that synthetic marijuana products are safe and legal has persisted despite a rash of media reports to the contrary. "There is a widespread misperception about the safety and legality of these substances," says Amelia M. Kasper, M.D., an epidemic intelligence service officer at the Centers for Disease Control and Prevention. "Not only among the general public, but among the medical and public health community."

In fact, the drug is crudely made. Concentrations of active ingredient can vary widely from one hit to the next, and some products have been found to contain other psychoactive substances such as phencylidine (PCP) and toxic chemicals such as formaldehyde.

Drug enforcement agents have struggled to shut down the synthetic marijuana market. "It's difficult to identify the people engaged in this sort of activity," says DEA spokesman Russell Baer. "They order the substances online, through black-market websites, and then have it delivered to vacant houses in their neighborhoods."

Likewise, doctors are struggling to diagnose and treat patients who turn up in their emergency rooms after taking SCs. There are no rapid diagnostic tests available, and just a handful of specialized research labs around the country that have the capacity to detect the compounds in human tissue. And so far, there is no antidote with which to treat overdoses.

"We don't know enough about the pharmacology or pharmacokinetics of these drugs to be able to provide specific patient care recommendations," Kasper says. Doctors at the CDC and elsewhere are working to better understand the synthetic cannabinoids that have flooded the streets.

In the meantime, experts say the best hope of curbing use is to spread this message as far and wide as possible: Synthetic marijuana is not the same thing as regular marijuana. The highs are different, dangerous, and can kill you.