PNNL researcher Ashley Bradley practices her lab work using a non-fentanyl substance. Bradley is part of the team working on the library of fentanyl variants. (Pacific Northwest National Laboratory / Andrea Starr Photo)

Nationally, fentanyl-related overdoses are the leading cause of death for Americans age 18 to 45. The drug killed almost twice as many people in this age group compared to automobile crashes, the second-leading cause, in the year ending April 2021.

Those impacts are reflected in law enforcement as well. The Seattle Police Department last year seized 10-times the number of fentanyl-based pills than were recovered the year before, according to news reports. Fentanyl use is threatening public safety, with drug users routinely smoking the opioid on buses and light-rail trains.

Now researchers at Pacific Northwest National Laboratory are using sophisticated technologies to provide first responders and law enforcement better tools for recognizing fentanyl in its many variants. They’re even predicting new forms that the shapeshifting drug might one day take.

Because just as the COVID-19 virus mutates into more infectious or dangerous versions of itself, illegal drug chemists are tweaking fentanyl’s properties. The synthetic opioid can be made more potent, more addictive, easier to cut into other drugs, and harder to identify and detect. It’s even possible to make it different enough to potentially duck its classification as a Schedule 1 or 2 drug, putting it in a legal gray area.

Rich Ozanich, PNNL analytical chemist. (PNNL Photo)

It’s hard to say how many fentanyl variants have already been unleashed, but “it is easily in the dozens and varies by geographic location and over time,” said Rich Ozanich, a PNNL analytical chemist based in Richland, Wash.

“Some variants are more prevalent than others, but new ones can appear unexpectedly,” Ozanich added, “and are sometimes only detected due to an overdose.”

In 2015, three people who overdosed in Seattle’s King County had fentanyl in their systems. Six years later, that number has spiked more than 100-fold, with the opioid present in 382 deaths in the county last year.

“It’s just astronomical,” said Brad Finegood, a strategic advisor for Public Health – Seattle and King County.

Building a drug library

Ingredients for the opioids are often made in China and manufactured into fentanyl in Mexico, experts say, then smuggled into the U.S. Fentanyl initially arrived in the greater Seattle area masquerading primarily as pain pills like Percocet and OxyContin. In other regions it was more commonly mixed with heroine or methamphetamine. It can be added to counterfeit Xanax and Adderall.

Now it’s being sought by drug users as fentanyl itself.

The opioid is produced and used legally to treat severe cancer pain. It’s roughly 50 times more powerful than heroine. It’s swallowed as a pill or smoked, lowering the bar for experimentation for people who balk at injecting drugs. It can be deadly in grain-of-salt-sized amounts, is relatively inexpensive and it’s increasingly killing kids, as well as people of all ages in urban and rural settings.

“It's super duper scary,” said Finegood, an expert in addiction issues. “We're doing everything in our power to get ahead of this.”

It's not easy. When public health officials are combating heroine, drug users come in for free, clean needles, providing an opportunity to talk about addiction treatment and other resources. That doesn't happen with fentanyl. Instead, Finegood's agency is using social media as a primary tool for education and outreach. A recent campaign had 13 million imprints.

Brad Finegood, strategic advisor for Public Health – Seattle and King County. (Public Health Photo)

The work at PNNL requires more advanced technologies.

Medics, police and other front-line workers responding to an overdose or crime scene can face unidentified substances that pose unknown threats. They use costly, mobile chemical detection devices to analyze the substances. But they're limited by the device's onboard database or "library" of known chemicals. With fentanyl, criminals keep adding unfamiliar volumes.

So the PNNL researchers built a library of 50 fentanyl variants, which is being shared for free with the 14 device manufacturers. By this summer, the companies' 21 different devices — including those already out in the field — should be updated with the new information.

Then the researchers are doing a sort of Consumer Reports evaluation of the devices, said Ozanich, who is leading the work. The team will test the devices against fentanyl that's mixed in 70 different combinations as it might be found on the street. That includes mixing it with other illegal drugs, laxatives and acetaminophen that are added to treat fentanyl's side effects, and other substances.

The detection devices can cost $50,000 or more and use technologies including analysis of the light reflected by the chemicals, test strips and by "sniffing" the air near a chemical.

The PNNL work is being funded by the Department of Homeland Security Science and Technology Directorate.

Predicting new threats

Kabrena Rodda, PNNL senior scientist. (PNNL Photo)

Another PNNL team is trying to get a step ahead of the drug dealers, predicting new fentanyl variants before they exist.

Kabrena Rodda, a PNNL senior scientist who leads multiple projects focused on chemical threats, estimates that there are millions of potential fentanyl analogues. The researchers are using computational chemistry and databases describing the metabolic and pharmacological effects of different drugs in order to predict the most likely variants.

The predictive technology will ultimately be applicable to other drugs and chemicals of concern.

For those working to beat back the fentanyl plague, it can feel like a battle that isn't going so well. Rodda thinks her group's work can provide some hope.

"Without some of these more predictive tools, I think it could feel very defeating,” she said. "The more quickly we’re able to respond [with law enforcement], then perhaps that leads to a world where the people who do this work decide it’s not worth it.”

It will still be a couple of years before information on the predicted fentanyl variants will become a tool for first responders and law enforcement.

But Rodda, Ozanich and Finegood emphasized the importance of staying on top of the evolving threat.

"We're keeping our finger on the pulse," Finegood said.

"If we see a new drug or new drug trend that comes up, whether it's drugs coming in different substances or a new drug that we haven't seen before, we want to let the community know," he said, "because that's a big risk.”

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