Experts question Health Canada claims over W-18 drug, call for more research

Experts are questioning widely circulated Health Canada claims that the drug W-18 is 100 times more powerful than fentanyl, or that the new arrival to the illicit-drug scene is even technically an opioid.

Dr. David Juurlink, head of pharmacology and toxicology at the Sunnybrook Health Sciences Centre in Toronto, said that while W-18 could very well be dangerous more research is needed before conclusions can be drawn about its chemical behaviour and potency.

"The main thing we know is that we don't know very much," Juurlink said in an interview. "It's clearly a chemical and it does something but what exactly it does is not clear."

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What is known is that W-18 is a synthetic compound created and patented at a University of Alberta laboratory as a potential pain reliever in the late 1970s and early 1980s. It was one of 32 chemicals produced in the so-called W-series, none of which were ever produced commercially.

As of June 1, Canada made it illegal to produce, possess, import, export or traffic W-18 after the substance was identified during several illicit-drug seizures.

Researchers looking at the chemical structure suggest the compound doesn't bind to opioid receptors in the body the way fentanyl or other opioids do, Juurlink said.

W-18 inventor responds

The inventor of W-18 also disputes the claims being made about the chemical. Retired chemist Ed Knaus said that while the other compounds in the W-series behaved in some ways like opioids, that same behaviour wasn't displayed in W-18.

"It's always possible (that it's an opioid) because we didn't prove the mechanism of action," Knaus said. He added that W-18 isn't necessarily 10,000 more toxic or dangerous than morphine.

"The problem here is that the press and everybody extrapolates (and) people start to equate numbers," said Knaus.

"They say that this thing is 100 times more potent than fentanyl and fentanyl is 100 times more potent than morphine, so automatically it's 10,000. Well, we never tested fentanyl in our case."

Knaus said he was "saddened and disturbed" that after so many years someone would exploit W-18 for use as an illicit drug.

BCCDC backtracks

The B.C. Centre for Disease Control has since backtracked on information it released in January describing W-18 as an opioid 100 times more toxic than fentanyl.

"That information was what was available to us back at the end of last year, and there has since been a lot more interest and some more supposition," said Jane Buxton, the head of the centre's harm reduction office.

Health Canada did not respond to a request for comment, but it appears the information included in its fact sheet comes from preliminary research in the original nine-page patent application, dated Aug. 28, 1984.

That same research information was circulated by the Centre for Disease Control, said the organization's head, Mark Tyndall.

The study used mice to test the pain-relieving activity of all the W-series compounds and the results were compared to several other drugs, including aspirin and morphine.

The research found it takes 10,000 times more morphine than W-18 to produce the same analgesic effect.

Catastrophizing W-18

That doesn't make the drug 10,000 times more dangerous than morphine, said Bryan Roth, a pharmacologist at the University of North Carolina.

"All this means is that if you're a mouse ... you could be given a dose of W-18 that's 10,000 times less than a dose of morphine and you would have basically an equivalent effect," said Roth, who is conducting research on W-18.

"It may be a dangerous drug, but we don't know that. There's no data out there."

It's prudent to be concerned about it though, given that a poorly understood compound is showing up on the illicit market, he added.

Roth raised the concern that if W-18 turns out to be toxic but not an opioid, then standard overdose-reversing agents such as naloxone would be ineffective.

Juurlink said there are plenty of other drugs to focus on that warrant the attention of police forces and regulators and doctors and end users.

"We should focus on them and spend less time catastrophizing on the issue of W-18."