Pubdate: Mon, 10 Aug 2015
Source: Washington Post (DC)
Copyright: 2015 The Washington Post Company
Author: Terrence McCoy


UNICORPORATED JACKSON COUNTRY, N.C - The chemist who unwittingly 
helped spawn the District's synthetic drug epidemic is a hard man to 
find. His phone numbers are listed under his wife's name. Strangers 
who call his laboratories at Clemson University are told he doesn't 
return messages.

To find him, you must travel deep into the Smoky Mountains and take a 
road that winds into the clouds. There, atop a mountain, you will 
discover a stooped, elderly man padding about a house cloaked in mist.

John W. Huffman is his name. But he is better known by his initials: 
JWH. In the world of synthetic drugs, few letters carry greater 
notoriety. They have materialized on thousands of advertisements 
selling what are known as synthetic cannabinoids or marijuana. And 
government authorities have banned nine JWH substances, making him 
arguably the nation's most prolific inventor of outlawed synthetic 
Huffman's compounds, experts say, laid some of the earliest 
groundwork for what has become a scourge of cheaply made, 
mass-produced synthetic drugs wreaking havoc in the District and 
beyond. Since the 1990s, when Huffman cloistered himself in a lab and 
forged hundreds of compounds for medicinal purposes, the synthetic 
marijuana industry has become an international, multibillion-dollar 
juggernaut that D.C. Mayor Muriel E. Bowser (D) calls a "serious 
threat to our public health and public safety."

The number of overdoses in the District has exploded in recent 
months, data shows. In May 2014, medical professionals handled 50 
overdoses. But in June, that number mushroomed to 439, resurrecting 
the ghosts of the crack epidemic that once ravaged the city, and it 
led to a citywide crackdown on the sale of synthetic drugs that were 
once available at gas stations and convenience stores for as little 
as $5 a pack.

Despite the growing diversity of these synthetic cannabinoids, 
primarily produced by Chinese chemists intent on staying one step 
ahead of drug authorities, experts say many of them share a common 
ancestor in Huffman's work. The blueprints that he and others 
published in academic journals led to hundreds of new species of 
drugs that authorities have struggled to track.

How that happened is a familiar tale of unintended consequences in a 
rapidly interconnected world. Like ecstasy or LSD, synthetic 
cannabinoids mark the latest example of a substance hatched in 
medical research that metamorphosed into a rampant street drug.

Huffman's work "is how it all started," said Marilyn Huestis, senior 
investigator at the National Institute on Drug Abuse who has known 
Huffman for years. "This is how it started. And it's a very sad thing 
that it's happened. They are now off and running. . . . John's very 
distraught that this has all happened."

Unexpected transformation

But on a recent Thursday afternoon, Huffman didn't seem particularly 
ruffled. He had just finished lunch. Clouds flitted across 
mountaintops outside his window. He nestled beside an old dog he 
refers to as "little girl" and let out a sigh. Then he began his 
story in an intonation as flat as the Illinois landscape where he was 
born 83 years ago.

He never expected this late-life transformation into an international 
drug figure. He never thought drug purveyors would one day solicit 
him for help. Or that online forums would enumerate his contributions 
to pharmacological adventure. Or that a Russian broadcaster would 
bring him on a show and accuse him of "trying to poison the youth of Russia."

His had once been an archetypal academic existence of research and 
teaching. Born in Evanston, Ill., he was always interested in 
chemistry and what it could mean for medicine. After getting his 
doctorate at Harvard University, he spent almost his entire career at 
Clemson University, where he raised four kids, married three times 
and published any synthetic chemistry research he could.

Meanwhile, big things were happening in the world of synthetic drugs. 
The biological reaction that marijuana triggers in the body had long 
been a mystery. Scientists could dissect marijuana's active component 
- - THC - tinker with its structure and conjure synthetic compounds 
based on that. But they did not know whether THC worked through 
non-specific interaction with cell membranes or whether it interacted 
with the brain's sensory receptors, which read neurochemical messages 
and tell cells what to do.

Then, in the late 1980s, came the discovery of something called the 
cannabinoid receptor, which confirmed the latter of the theories. 
This was the system that THC stimulates. But it was much more than that.

"We can't function normally without these [cannabinoid] receptors," 
Huestis said. It's an aspect of the brain that humans brought with 
them from the earliest days of evolution, she said, modulating things 
such as executive function, appetite and memory. "It enables us to do 
all the things we do."

Its discovery marked a crucial moment in the development of synthetic 
cannabinoids. Rather than fumbling around in the dark, chemists could 
aim for a specific target-the cannabinoid receptor. Pioneering 
researchers started synthesizing fresh compounds to see how the 
receptor reacted to them.

"It took the black-magic aspect of marijuana's activity and gave it a 
biomolecular mechanism in your body," said Brian F. Thomas, a 
principal scientist with RTI International, a research institute. 
"Because you had this cannabinoid receptor, you could then look and 
find new compounds that can bind to that receptor."

A puzzle to solve

Around that time, Huffman learned of the nascent research. He was 
shocked. These synthetic compounds interacted with the cannabinoid 
receptor just like THC but looked nothing like THC. It was a chance, 
he thought, to study something completely new.

The cannabinoid receptor, he said, represented a "puzzle." How did it 
work? And the only way to solve it was by examining its interactions 
with different synthetic compounds. So, Huffman got to work. Funded 
by the National Institute on Drug Abuse, he produced hundreds of 
synthetic cannabinoids, so named because of the way the drugs 
interact with the receptor, not because they emulate the side effects 
of marijuana.

"These compounds that Huffman made were pharmacological tools - tools 
we can use to understand what's happening in the brain," Huestis 
said. "He created an entire line of chemicals . . . that enlightened 
us so much."

But a strange thing can happen to scientists when navigating the 
frontiers of knowledge. It is easy to lose sight of outside 
applications. At the time, Huffman's second wife had just been 
diagnosed with multiple sclerosis. He was so preoccupied, he said, by 
the immediacy of his work and home struggles that he never realized 
he was unwittingly writing a recipe book of street drugs.

"The chemistry to make these things is very simple and very old," 
Huffman said. "You only have three starting materials and only two 
steps. In a few days, you could make 25 grams, which could be enough 
to make havoc."

The exact chronology of what happened next is hard to pin down. What 
is known, however, is that Huffman synthesized one compound called 
JWH-018 in 1993 and published the formula in a series of papers, 
journals and a book called "The Cannabinoid Receptors."

It is unclear which article the underground chemists used or when 
they found it or who they were. But by late 2008, the compounds that 
had originated on Clemson's campus were identified 4,500 miles away 
in a forensic laboratory in Germany. The manufacturers had sprayed 
the synthetic cannabinoid onto plant leaves and sold it - along with 
several other cannabinoids - under the name Spice. JWH-018 was the 
"first synthetic cannabinoid to be identified as a product adulterant 
in Germany," the Drug Enforcement Administration said in a report.

Huffman's compounds soon became dominant. They were so easy to make, 
experts say. "Let's say you're a criminal mind," Thomas said. "You 
want to make a million dollars. And you say [to a chemist], 'I want 
you to make this.' They'd say, 'Come back in a year.' But you could 
bring John's compounds, and they'd say, 'I'll have 10 grams for you 
in two weeks.' "

Huffman recalled the first time he heard about the drugs. A German 
blogger, he said, had sent him a news article describing a new drug 
one man had smoked. It was called Spice. The active compound: JWH-018.

"I thought it was sort of hilarious at the time," Huffman said. "Then 
I started hearing about some of the bad results, and I thought, 'Hmm, 
I guess someone opened Pandora's box.' " He had never intended anyone 
to use those compounds, and in that moment, he realized the potential 
ramifications of his work.

More horror stories

The horror stories piled up. One Iowa kid in 2010 smoked too much 
synthetic marijuana, told his friends he was "going to hell," then 
shot himself. An Indiana woman's death that same year was blamed on Spice.

The number of calls to poison-control centers involving synthetic 
cannabinoids soared from 112 in 2009 to 6,549 in 2011, according to 
the American Association of Poison Control Centers. During that same 
period, national statistics show forensic laboratories turned up 
JWH-018, JWH073, JWH-200 - as well as two other synthetic compounds - 
5,450 times.

So the DEA in 2011 banned a list of synthetic cannabinoids. Three of 
the five were Huffman's.

David Nichols, a chemist at Purdue University, knows what it is like 
to publicize a substance now associated with death. Before MDMA (also 
known as ecstasy) was popular, he studied it in the hopes that drugs 
like it could help in psychotherapy. He published three papers on a 
structurally similar molecule called MTA. But then, he says, some 
European chemists got their hands on the work and produced MTA for 
consumption. By 2002, six deaths were linked to MTA.

Those deaths haunt Nichols, who has since declined to publish a 
synthesis he feared underground chemists could exploit. "The fact 
that this killed a bunch of people, I was like, 'Oh my God, how did 
this happen?' . . . It's a tragedy if they end up having an accident 
or overdosing. I don't think they're dumb. I think it's a tragedy."

Huffman, too, feels a tinge of regret. But not because of the havoc 
his synthetic cannabinoids unleashed. He derides synthetic-drug users 
as "idiots" for getting into something never tested on humans. What 
discomforts him, rather, is all the unwanted attention he has since gotten.

"I don't want pest calls," he said. "I get a number of them that are 
nut calls. You know, 'Why did you make the compound that murdered my 
son?' and this sort of stuff. I've had e-mails like that. There's a 
reason I'm so difficult to reach. I want it that way. . . . It's a nuisance."

Thankfully, he said, those calls have decreased in number over the 
past few years. His elusiveness helps explain that. But forces beyond 
Huffman also have diminished his stature in today's synthetic 
marijuana industry. When authorities banned his compounds, a rush of 
new ones filled the void.

The progression has worked like an evolutionary tree. The first and 
second generations of cannabinoids shared many characteristics with 
Huffman's. But as the tree widened, new compounds that emerged had 
less in common with their forebears. The most prominent synthetic 
cannabinoid today, said DEA supervisory chemist Jill Head, is XLR-11, 
which is very different from Huffman's JWH series. "This has been an 
evolution," she said, "and it had to start somewhere."

On a recent afternoon, as rains moved across the mountains outside 
Huffman's escape, the chemist said nothing can stop what he helped 
create. Ban one substance, another will take its place. Cleanse the 
streets, the drug moves to the Internet.

"If someone wants to get high," he said, "they're going to figure out 
how to get high."
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MAP posted-by: Jay Bergstrom