New class of opioids potentially more effective than fentanyl | Opioid crisis

A new class of potentially deadly synthetic opioids is suddenly appearing all over the world, including in the United States, and scientists are currently trying to figure out how to detect these substances in the drug supply.

In the last month, Nitazene has been linked to four overdose deaths in Manchester, England; it has been detected in over 2,500 counterfeit oxycodone tablets in Hamilton, Canada; and it has been found for the first time in the Netherlands. The US Drug Enforcement Administration has warned of its emergence in Washington DC.

Nitazenes are a class of synthetic opioids that were first developed in the 1950s but never approved for market.

Claire Zagorski, a doctoral student in translational sciences at the University of Texas at Austin who specializes in drug testing, said that after drug companies gave up on nitazen, “they filed the patent, they filed the synthesis and put it on a shelf, and then people dug it up on the illegal market.”

Nitazene was first discovered in the United States in 2019 and appears to have spread rapidly over the past year.

Christophe Stove, a professor at the toxicology laboratory at Ghent University in Belgium, said all the “ingredients” were there for nitazen to spark a new drug crisis. The Taliban recently banned poppy cultivation in Afghanistan, which has led to a shortage of heroin on the illegal drug market, particularly in Europe, where heroin is still more popular than fentanyl. For illegal drug suppliers, nitazen could be a cheap and easy way to fill that gap.

Zagorski studied how isotonitazene, one of the most commonly detected nitazenes, is synthesized to understand its viability in the synthetic drug market. She found that it is cheap to manufacture using legally available ingredients.

Nitazenes are also a cost-effective alternative because some of them are much more potent than fentanyl, which is already about 100 times more potent than morphine. According to Stove, whose lab has studied most of the known nitazenes as well as some that may emerge in the near future, animal studies confirm that the most potent nitazen known, etonitazene, is “about 40 times more potent than fentanyl.”

He said other nitazens have varying potencies depending on their exact chemical structure, ranging from slightly weaker than fentanyl to significantly stronger.

This high potency raises a number of challenges. Richard Bade, a senior research fellow in environmental science at the University of Queensland in Australia, conducted a study to determine whether nitazene could be detected in wastewater – a method also used to determine Covid-19 levels in the population.

Bade said nitazene is “quite challenging” because its potency means “the concentrations in wastewater can be very low, even when it is known to be present in a community.” His study found that it is possible to detect nitazene in wastewater, but more sensitive methods are required than for other substances.

The high potency of some nitases also makes them more dangerous for people who use them. Stove said some pills can contain a lot of nitase powder if the illegal manufacturers don't mix them properly: “If you're unlucky enough to get some that have more of it in them, you can overdose,” he said.

Nitazenes are especially dangerous when people don't know they're taking them. Stove said that until recently, most Nitazene users specifically searched for them online. But today, Nitazenes are showing up in street drugs marketed under other names, such as Xanax or oxycodone. Someone who hasn't developed a tolerance to opioids and thinks they're taking another drug is more vulnerable to overdose when exposed to high-potency opioids like Nitazenes.

Test strips are a cost-effective way for people to determine if their drug supply contains undeclared substances.

“It's very simple. It's a little strip that you dip into the liquid you've prepared to inject your medication or smoke or whatever,” Zagorski said. After dipping the strip, you wait to see if a line appears indicating a positive result – the same concept as a Covid test or a pregnancy test.

Harm reduction organizations often distribute fentanyl test strips to prevent overdoses. However, fentanyl test strips do not detect nitazene. Although the two drugs have similar effects, nitazene is chemically different enough from fentanyl that it cannot be detected on fentanyl test strips.

One company already makes and sells Nitazene test strips, although they are not yet widely available. Stove and his colleagues worked quickly to publish a study this month looking at whether the strips are functional enough to be helpful.

“I instructed my graduate students to really prioritize this project because we really felt that this information needed to be communicated to the users of these strips,” Stove said. The study found that the test strips were generally effective, although they may not detect every type of Nitazene. “If you don't get a positive result, that doesn't mean the drug is safe, but that's true of all drug tests with test strips,” Stove said, emphasizing that the strips can only test for one substance at a time.

The gold standard for drug testing, Zagorski said, is expensive, sophisticated instruments such as gas chromatography/mass spectrometry machines. But, she said, these machines are expensive to operate and “there's not a lot of money in harm reduction.” In Texas, where Zagorski's lab is located, drug testing equipment such as GC/MS machines and drug test strips are illegal.

Zagorski is happy that European researchers like Stove are also working to better understand and identify nitazene.

“Europe has much more advanced laws in this regard and can do the testing much faster,” she said. In the US, “investigating the drug supply is objectively useful, but it still has a certain air of suspicion, like, 'Why are you investigating this?'” she added.