John W. Huffman

In December 2008, John W. Huffman, a professor of organic chemistry at Clemson University, received an e-mail that illustrates how pure scientific research can be exploited in unintended ways. The e-mail, from a blogger in Germany, alerted Huffman to the fact that the synthetic cannabinoid JWH-018 had been detected as an ingredient in some herbal blends marketed over the Internet as a legal substitute for marijuana.

Huffman knows JWH-018 well. “We made the stuff in 1995,” he says. “I had an undergraduate student working under the supervision of a very capable postdoc, and this was just one of the things we made.” Their research was published in 1998 in the Journal of Pharmacology & Experimental Therapeutics (1998, 285, 995).

JWH-018 is the 18th compound that Huffman’s research group synthesized in a series of more than 470 analogs and metabolites of ∆⁹-tetrahydrocannabinol (THC), the active component of marijuana. Huffman created these compounds to study their interactions with the cannabinoid receptors in the brain. All of the compounds bear his initials, “JWH.”

Since 2008, more than a half-dozen countries have banned herbal blends containing JWH-018 and other synthetic cannabinoids. Other nations are also considering outlawing the mixtures, which are sold under names such as “Spice” and “K2.” In the U.S., Kansas recently banned K2, and several other states are considering similar legislation. JWH-018 is not currently regulated under the Controlled Substances Act, but the U.S. Drug Enforcement Administration has designated the compound a drug or chemical of concern.

“I wasn’t the least bit surprised,” Huffman says of learning that JWH-018 was being sold for recreational use. “Somebody is going to look for something to make money from and to bring people temporary pleasure,” he says, adding that those making and selling JWH-018 don’t face as many legal consequences as those selling marijuana—at least not yet.

He suspects that the perpetrators used his published data as a basis for synthesizing JWH-018. “You put two and two together,” he explains.

Other compounds Huffman and his colleagues created, such as JWH-073, have also been discovered in herbal blends. He notes that JWH-073, which has a butyl group on its nitrogen rather than a pentyl group, is less potent than JWH-018. JWH-073 and other similar compounds are likely added into the herbal blends “to make it harder to identify what’s in there,” he says. But law enforcement agents have chemists like Huffman on their side. And, as he points out, a tandem gas chromatograph-mass spectrometer goes a long way.

Huffman believes that JWH-018 is the more widely used synthetic cannabinoid in the JWH series because it “has the combination of being quite potent and easy to make.” But other compounds found in these herbal products are much more potent than JWH-018, he says. One example is HU-210, a compound also known as (–)-1,1-dimethylheptyl-11-hydroxy-∆⁸-tetrahydrocannabinol that was first synthesized by researchers at Hebrew University of Jerusalem.

Huffman says that some of the commercially available JWH-018 products that local law enforcement agents have sent him to analyze were far purer than the original version that his research group made. “We reported it as an amber-colored gum, and these people are getting it as a solid,” he says of the compound. “I suspect that they purify it by some sort of automated chromatography, and we used a classic column.”

The most difficult part of this situation, Huffman notes, is hearing the stories from parents and relatives of people who have gotten sick or died from using herbal mixtures containing JWH-018. Still, he feels no remorse about creating the compound. “You can’t be responsible for what other people do,” he says. “We made this as a research compound and published it and did what we were supposed to do. You can’t stop people from being idiots.”

He is concerned, however, about the unknown health effects of JWH-018. “Using these things is like playing Russian roulette because we don’t have toxicity data, we don’t know the metabolites, and we don’t know the pharmacokinetics,” he says.

As news of JWH-018 spreads, Huffman is becoming increasingly inundated with media requests and queries for analytical help from law enforcement officials. He’s even been asked to serve as a consultant and expert witness in Canada, and he’s been invited to attend forensic chemistry meetings. The new activities, Huffman jokes, “will give me something to do after I retire,” which will take place at the end of September. “This will keep me out of mischief,” he says.