"These things are dangerous — anybody who uses them is playing Russian roulette," Huffman said. "They have profound psychological effects. We never intended them for human consumption."
But after Huffman's team published its work, opportunists who saw a ready market in stoners seeking stronger highs grabbed the formulas. They mixed the pale, amber, gummy compounds with benign herbs to resemble marijuana.
Huffman said he first got calls in early 2009 about head shops selling products based on his formulas.
Although he was irritated that people were smoking his creations to get high, he was not entirely surprised.
The effects of JWH-018 can be 10 times stronger than those of THC, the active compound in marijuana. Some of his more complex compounds are even more potent, he said, and carry an even higher risk of hallucinations and psychosis.
"I always had a hunch that someday somebody would say: 'Hey, let's try smoking them.' And lo and behold, that's what happened," he said.
Huffman said other cannabinoids among the 460 are very difficult to make, even for scientists. But the three of his compounds outlawed by the DEA — especially JWH-018 — are easily produced.
"You can make them in two steps from commonly available starting materials, which is why people jumped on these ones," Huffman said.
Most of the chemicals are imported from overseas manufacturers — especially in China — but underground labs in the U.S. increasingly are producing and synthesizing them, said Payne, the DEA spokesman.
The agency is investigating several large-scale importers and distributors, said agency spokeswoman Barbara Carreno. In August, authorities in Louisiana seized 7,200 grams of synthetic marijuana intended for sale at $25 to $30 per packet, for an estimated street value of $80,000 to $130,000. The products had names like White Widow, Cajun Spice and Voodoo Remix.
But the DEA doesn't have the resources to study all 460 of Huffman's compounds, plus those created by others, Carreno said. That means any products containing cannabinoids other than the five listed by the DEA technically remain legal.
If the Department of Health and Human Services recommends outlawing the five listed cannabinoids, they would remain illegal for six months. The DEA would then begin public notices and other bureaucratic procedures to permanently outlaw them. Steps to make other cannabinoids illegal could follow.
Huffman supports banning them. But he also favors legalizing and taxing marijuana.
"You can't overdose on marijuana, but you might on these compounds," he said. "These things are dangerous, and marijuana isn't, really."
Huffman recently retired from Clemson, but keeps an office at the university. He mainly spends his days in the idyllic hamlet of Sylva, where his back porch offers spectacular mountain views. He still gets phone calls "from little papers in East Podunk, Ark.," he said, asking about the potent fake pot he supposedly invented.
Huffman's real scientific legacy is his research on brain and central nervous system receptors. If you want to talk about "really good stuff," he said, consider JWH-133, another compound his team created.
"It's the best stuff we've done in terms of scientific value," he said.
The compound has been shown, in mice, to shrink brain tumors and lead to regression of non-melanoma skin cancers, suggesting a potential use in chemotherapy.
Huffman has never considered smoking his compounds, but he did smoke marijuana — once. It was in the mid-1990s, at a research conference in Arizona.
Two researchers flew in from Amsterdam with "very high-quality Dutch hash" tucked into a matchbox, he said. They offered. He smoked — scientific curiosity prevailed.
The effects were similar to two-and-a-half martinis, he recalled. And the smoke burned his throat.
"I decided to stick to martinis," the professor said. "They're legal."