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This Is U-47700, Once a Lab Experiment, Now a Killer Opioid

From the Wall Street Journal:

In a high-stakes game of cat-and-mouse, overseas labs are churning out new synthetic drugs at a furious pace, often staying a step ahead of authorities and helping to fuel America’s rampant opioid crisis.

The United Nations Commission on Narcotic Drugs estimates that “new psychoactive substances”—a broad list that includes synthetic opioids—are emerging globally at an average rate of one a week. As with U-47700, rogue chemists sometimes piggyback on research by legitimate scientists that was abandoned before making it to the legal market.

Synthetic opioids are often more deadly than other kinds of common designer drugs, such as artificial cannabinoids or stimulants known as bath salts. Some opioids have flared up before—fentanyl variants caused problems on the West Coast in the late 1970s and 1980s—and they are roaring back at a perilous time.

The designer opioids mainly come from Chinese labs, the DEA says, and many labs sell them openly in online drug bazaars. On online forums, people compare notes on their experiences using the synthetics.

The U.S. surveillance system for these chemicals is a largely informal network of crime labs, medical examiners and law-enforcement authorities who share clues and alert each other when they find something new. It can be a laborious task, slowed in part by the challenge of finding something they didn’t know they were looking for.

At least six states specifically banned U-47700 before the DEA announced plans in September to make the drug illegal. DEA spokesman Rusty Payne said the agency’s scheduling actions are subject to “exhaustive reviews,” which take time.

So far this year through September, NMS Labs, a major private lab outside Philadelphia that works with states around the U.S., has tallied 105 overdose deaths related to U-47700 and 265 fatalities related to furanyl fentanyl—an analog, or chemical compound that is closely related to fentanyl. Axis Forensic Toxicology, a private lab firm in Indianapolis, has seen another 20 deaths linked to U-47700.

The U-47700-related fatalities span at least 31 states from Alaska to Utah to Florida.

The origins of U-47700 date to 1973, when Upjohn Co. asked its scientist Jacob Szmuszkovicz to create a drug with the pain-relieving power of morphine, but without the risk, according to a chapter he wrote for a 1999 book on drug research. Researchers wanted to find the Holy Grail that is elusive to this day: potent pain relievers that don’t have dangerous side effects, such as addiction and a potentially fatal slowdown in breathing.

By about 1974, Dr. Szmuszkovicz created a chemical Upjohn dubbed U-47700 at a company lab in Kalamazoo, Mich. Researchers knew it was a morphine-like drug when it triggered erect tails in mice, a reaction known as a Straub tail, says Phil von Voigtlander, a retired Upjohn research director who worked on the project.

Another test, which involved shining a hot light on mice’s tails to judge how long it took them to move, helped measure U-47700’s potency, says Dr. von Voigtlander. He learned the compound worked on the same receptor as morphine with roughly 7.5 times the strength.

Further rodent testing also revealed a downside. “Once we saw that it just caused tolerance and dependence like opioids and had opioid side effects, we thought, well, that’s just another morphine and that’s not what we’re looking for,” Dr. von Voigtlander says.

He calls U-47700 an important research steppingstone, and Upjohn patented the chemical. The company never tested U-47700 on people.

These kinds of pharmaceutical research efforts leave behind copious patents and scientific papers, which can serve as recipes for today’s enterprising chemists. Some researchers believe Chinese labs are scouring patent literature for new synthetic compounds to produce, before selling them.

Foreign labs began making U-47700 and offering it for sale online by late 2014, according to a forum on the social-media website Reddit devoted to discussion of chemical vendors and frequented by drug users. Buyers can choose from an array of online vendors selling synthetic drugs, including opioids, dubbed “research chemicals.”

The websites typically carry warnings that the chemicals they sell are “not for human consumption”—an attempt to gain legal cover, authorities say—and that buyers are responsible for complying with their home countries’ laws.

U-47700 began claiming lives in the U.S. by May 2015, when a 28-year-old man overdosed in Knox County, Tenn. The medical examiner there initially pegged his death to oxycodone, which was in his system. It took many more months to discover U-47700 was also there.

First, labs had to figure out what the drug was. NMS Labs detected U-47700 in November 2015 while testing blood samples from four different states at its facility outside Philadelphia.

“We actually found it by accident,” says Barry Logan, chief scientist there. U-47700 closely resembles a synthetic opioid called AH-7921—another research relic—which NMS had started watching for last year.

NMS, which is now rushing to create new tests to screen for 21 different designer opioids, eventually linked U-47700 to the Knox County case.