LEADING UAMS' STUDY: Paul Prather says even many fellow scientists wrongly think of K2 as 'fake marijuana.' Brian Chilson

When he talks about K2, University of Arkansas for Medical Sciences researcher Keith McCain asks people to imagine a room full of drugs. In the room there is cocaine, heroin, methamphetamines and a bevy of other familiar, deadly substances. In the corner, there’s K2. About to enter are his children. But before his children go into the room of drugs, McCain is given an opportunity to remove just one drug.

“I would take out K2,” he says.


McCain is one of the five investigators attached to a $2.7 million grant to study the toxicity of synthetic cannabinoids such as the ones that make up the multiple substances called K2.

When Paul Prather, who is leading UAMS’ K2 study, first attempted to get funding to study synthetic cannabinoid toxicity, even some scientists reviewing the proposal were confused. Everyone thought of synthetic cannabinoids and K2 as squarely in the realm of “fake marijuana,” Prather said.


“We would get review comments like, ‘Well, you know these products are not going to be toxic. I mean marijuana — no one has ever died from an overdose of marijuana,’ ” Prather said. “But that’s not at all what these products are … these compounds are not safe and they’re not marijuana; they have nothing to do with marijuana except they bind to the same site.”

That site is, primarily, a cell membrane receptor called CB1. That, and CB2, are the receptors to which THC (tetrahydrocannabinol), the psychoactive ingredient in marijuana, binds. THC creates many effects, from relief of tension in the eye caused by glaucoma to the high that recreational users seek.


In research to produce the medicinal, rather than psychoactive, effects, scientists began synthesizing chemicals that operated similarly to THC — synthetic cannabinoids.

But the science of creating synthetic cannabinoids for medical benefit went off the rails. Consider John W. Huffman, a chemist cloistered in his lab at South Carolina’s Clemson University throughout the 1990s, who cranked out paper after paper identifying synthetic cannabinoids. Huffman would publish the synthetic cannabinoids, labeling them in papers with his initials, JWH.

People Prather calls “clandestine chemists” — who might have a degree in chemistry, but usually are not professional chemists — “look[ed] at these published articles and [saw] here are these thousands of chemicals they can synthesize in their lab.”

“They don’t know what they do — all they know really about them is they bind to the CB1 receptor,” Prather said. “Well, if they bind to the CB1 receptor like THC, you can probably assume they activate the receptor.” The amateur chemists knew they might get you high.


While Huffman and other scientists were slowly accruing knowledge about more synthetic cannabinoids and continuing the long, rigorous process of finding what they do, these “clandestine chemists” — often in Russia and China, Prather said — skipped ahead to human testing. They read the papers, created the drugs and gave them out for people to ingest.

By 2010, Huffman was getting calls from law enforcement officials about one of his compounds, JWH-018. His initials, and those of other scientists who have developed cannabinoids, had become commonly discussed by K2 users as they attempted to suss out the variants of the drug they liked best.

“I thought it was sort of hilarious at the time,” Huffman told The Washington Post. “Then I started hearing about some of the bad results, and I thought, ‘Hmm, I guess someone opened Pandora’s box.’ ”

Here are the results of some of these rogue human tests: 439 overdoses in June 2014 in Washington, D.C.; nearly 120 overdoses in five days in Texas in 2014; 6,000 emergency room visits and two deaths in Brooklyn in 2015; 15 hospitalizations in one weekend in Los Angeles in 2016.

Few statistics on K2 usage in Arkansas are available. The state Department of Health does not track overdoses or hospitalizations related to K2. The State Crime Information Center tracks K2 arrests under the broad category of “other hallucinogens.” In 2016, there were 19 arrests for possession and four arrests for the sale and manufacturing of “other hallucinogens.” The Poison Control Center in Arkansas received 101 calls in 2015 and 44 in 2016 related to K2, but this only accounts for those who voluntarily called looking for help. The state Crime Lab, which aids law enforcement agencies throughout the state, records instances when a synthetic cannabinoid has been identified in the course of an investigation. From Jan. 1, 2017, through March 31, 2017, the lab recorded 64 number of K2 incidents. Since the agency began collecting data on K2 in 2010, the number of incidents it recorded peaked in 2012 at 608.

Huffman did not realize that what he’d created in synthetic cannabinoids was fundamentally different than marijuana. Prather’s team’s task is to discover how K2 affects people.

Scientists are still struggling to just identify most compounds, let alone learn what they do.

“You got a thousand chemicals that nobody has ever tested; clearly you’re going to get a myriad of effects,” Prather said.

Prather’s group, which is in the second year of the five-year grant, is using as a jumping-off point previous findings by others that K2 products, also called “spice,” can cause psychosis, seizures, tolerance, dependence and death.

“People know how people typically react when they smoke marijuana,” said Jeff Moran, another member of the UAMS team. “This is the first time we’re really seeing the use of these types of cannabinoids in humans. And this is the reason why we’re seeing death, suicides; I mean, you name it.”

You can smoke K2 12 times and feel fine, then get a batch with the compounds combined in such a way that the effects are harmful. Prather’s group’s initial findings also indicate that synthetic cannabinoids may create worse effects over time for users because of the way the compounds are metabolized in the body: They stick around in your system. “You get kind of an accumulation and a snowball effect,” Prather said. “The main compound comes in and then these active metabolites — that have been formed [by previous use] and accumulated — [combine] and you get even greater toxicity.

“I think the first line of understanding is there’s nothing common about K2,” Moran said. “We just simply never know what we’re dealing with … . I’ve worked several death cases not only here in the state of Arkansas but, unfortunately, across the U.S.

“It is not marijuana. It is not safe and it can kill you,” he said.

The appeal of synthetic cannabinoids to prisoners is not exclusive to Arkansas, or even the United States. A study in the International Journal of Drug Policy, “Adding Spice to the Porridge: The development of a synthetic cannabinoid market in English prison,” argues that “the avoidance of detection of drug use” is the “primary motivation for the consumption of synthetic cannabinoids in prison.”

The paper also notes that, beyond deaths or personal harm, K2 use is having causing disturbances in English prisons.

It says that a 27 percent increase in assaults, a 31 percent increase in serious assaults, a 36 percent increase in rise in violent incidents against staff, a 25 percent increase in self-harm incidents, and a 27 percent increase in suicides are all “primarily attributed to the consumption of synthetic cannabinoids in prison.”

Prather doesn’t want to keep his findings just in the lab.

“When you start hearing these stories … . I mean that’s when it really affects you. This is not just something you can report on or something I can investigate. It really affects people,” he told me.

People should know, Prather says, that K2 can be deadly. And, that researchers are looking for solutions.

Prather said CB1 antagonists have been developed — and even tested clinically — that could potentially be used in emergency situations to stop seizures or other acute reactions to synthetic cannabinoids.

Moran is trying to make synthetic cannabinoid testing for labs easier and cheaper in Arkansas through an LLC laboratory called Pinpoint Testing.

“We’re in the final stages of receiving clinical accreditations for our test. And once we receive those accreditations we’ll be able to launch and go live and offer, you know, at least some specialized testing at reduced rates in comparison to other commercial entities that have picked it up,” he said.

In many ways, Arkansas is ahead of the curve, Moran said.

“I know this may sound crazy — but the problems that we are currently dealing with in Arkansas are in large part small in comparison to some other states that haven’t had such a good response. So Arkansas has done a very good job of responding to” K2 abuse, he said.

UAMS has created a task force working to disseminate K2 information.