Edmonton doctor warns dangers of W-18 are still a mystery

Police, doctors and scientists have called W-18 a synthetic opiate 100 times more potent than fentanyl and 10,000 times more powerful than morphine.

But it turns out that might not be true.

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Dr. Hakique Virani, a public health doctor in Edmonton, has been among those warning of the dangers of the drug.

In a CBC Radio interview in April, he said the amount of W-18 found in Edmonton earlier this year during a drug bust would be enough to kill the population of Alberta 45 times over. But now he says he spoke too soon.

While W-18 is still potentially highly lethal, how it affects users is largely unknown.

"We don't know if it can kill you, and if it can, we don't know how it does that, and we don't know if it would get somebody high," he said. "There are a lot of unknowns around W-18 and I think from a public health perspective we, including myself, were pretty irresponsible to jump the gun and say this is what W-18 is, and this is what it does, and this is how toxic it is.

"Because now if people have knowingly been exposed to W-18 and not died we've just created an invincibility complex and they may be more reckless with their drug use."

Not a known opioid

New research to be published later this week out of the Roth Lab at the University of North Carolina has found that W-18 does not trigger any of the opioid receptors in the brain. That means it is not a pain reliever like morphine or fentanyl.

Bryan Roth, a pharmacologist who heads up the lab, has tweeted some of the preliminary findings.While the specific dangers of the drug to humans is still unknown, Roth tweeted that the compound "seems quite toxic."

This research would overturn previous claims from now-retired University of Alberta pharmacology professor Ed Knaus, who created and patented 32 drugs known as W-compounds, one of which was W-18.

The patent, issued in 1984, describes the test done on lab mice to find out if the W-compounds could be used as a painkiller. The researchers looked to see if mice who were given a stimulus that caused them to writhe in pain would stop that reaction once they were given the compounds.

But Virani said this research from over 30 years ago is not enough evidence to draw the conclusions that many scientists and doctors did when W-18 resurfaced as a street drug.

"The reason we described the potency that we did was that the concentrations of W-18 that were required to dampen that writhing response, as compared to the same response with morphine, was one- ten-thousandth the concentration. But really you could stop a mouse from writhing by any number of mechanisms, including bashing it over the head with a mallet," he said.

"You could get it high on pot, you could give it anti-inflammatories, you could give it stimulants like cocaine or methamphetamine. But it doesn't tell the mechanism by which that writhing response is dampened, or what the mouse is feeling."

Roth, on twitter, also pointed to a study that found that a histamine trigger had a similar result in a writhing test on mice.

David Juurlink, a toxicologist and physician in Toronto, who has been sounding the alarm on W-18, said that his previous statements now seem overblown.

"I would be very surprised if W-18 is eventually found to have activity at opioid receptors," he said. "The main thing we know about W-18 is we don't know much about it."

What is W-18?

Aside from the compound structure and the results from animal testing, almost nothing is known at this point about the toxicity and effects of W-18 on humans.

While the compound has been called a fentanyl analogue, it does not look like fentanyl or morphine. Brian Escamilla, a forensic chemist in California, said the compound has an entirely different chemical structure.

"That's what made it unique," he said. "The fact that if it did bind to opioid receptors, that it was a completely different compound. As a matter of fact, some people have said that it's really not an opiate drug because it didn't have the same morphine backbone.

"The only reason it was considered a synthetic opiate is that it was estimated that it would bind to the mu receptor or one of the opioid receptors,' he added. "But it does look structurally different from the other opiate drugs that we've had in the past."

In an interview with Forbes magazine, one of the graduate student researchers who worked with Knaus at the University of Alberta 35 years ago said that, during the animal testing process when the mice were given some of the compounds, they fell unconscious for as long as five days.

Juurlink said these findings would have been surprising.

"When they gave this stuff to mice, the mice stood up for a minute and then passed out for three days and then woke up there afterwards,' he said. "That is not behaviour we associate within an opioid.

"It's chemical, and it probably does something, but what exactly it does is not clear at the present time," he said.

Last Friday, Calgary police confirmed the first overdose death linked to W-18. But the 35-year-old man who died in March also had heroin and 3-methyl fentanyl, a drug similar to fentanyl but stronger, in his system.

• Alberta's first fatal overdose linked to W-18 confirmed in Calgary

Escamilla said the case is similar to previous instances of overdoses linked to W-18.

"Most of the cases I've seen is W-18 cut up with something else because the dose is so small you have to cut it up with something," he said.

"The fact that W-18 has been seen with other drugs makes it very difficult to pinpoint W-18 as being the sole cause of death, especially when it's a cocktail of multiple drugs."

The real killer

The chief medical examiner's office has reported 274 fentanyl-related deaths in Alberta in 2015. British Columbia declared a public health emergency earlier this year after 200 fentanyl-related overdose deaths in 2016 alone.

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"The focus on W-18 is misplaced," said Juurlink. "We should be talking more about prescription opioids and fentanyl and bootleg fentanyl in particular because that is where we're going to see a lot more deaths in the years to come."

Virani echoed the same concern after learning the news of the recent overdose death in Calgary.

"The scary part of this recent death is that now we know 3-methyl fentanyl is circulating and we know that 3-methyl fentanyl is much more potent than fentanyl," he said.

He added: "Anybody who tells you we know anything about the potency of W-18 is lying and I was one of those people."