A medical examiner announced on Thursday that music legend Prince died of a self-administered dose of the synthetic opioid fentanyl, unleashing a torrent of headlines about the dangerously powerful narcotic that is “sweeping the U.S.”
Fentanyl isn’t a new drug. It began its long run as a first-line surgical analgesic in 1968, and since the introduction of the transdermal patch in the 1990s, has become one of the most commonly prescribed narcotics for treating moderate-to-severe cancer pain.
However, its profile as a street drug has grown precipitously over the past several years, as America has found itself in the grips of a crippling epidemic of opioid abuse.
State and the federal lawmakers are now considering increasing mandatory prison penalties for fentanyl distribution—bucking a bipartisan trend toward drug sentencing reform.
On Tuesday morning, members of the Senate Judiciary Committee are holding a hearing titled “Deadly Synthetic Drugs: The Need to Stay Ahead of the Poison Peddlers,” to consider solutions to an increase of deaths attributed to synthetic drugs like “K2” (a synthetic cannabinoid also known as “Spice”) and fentanyl.
Authorities are now looking into where Prince obtained the fentanyl that killed him. If it came from a physician, the pop star would be among a small minority of drug abusers who obtain fentanyl either directly through, or diverted from, pharmaceutical channels. Instead, according to the Centers for Disease Control, most of the fentanyl taken off the street to date has been “non-pharmaceutical fentanyl” (NPF)—most of which is manufactured clandestinely in Mexico.
Recently, though, public health officials have been sounding the alarm about a troubling spate of overdose deaths tied to more arcane fentanyl analogs—as well as other synthetic opioid derivatives—that are shipped legally from facilities in China.
There are now more than 30 analogs of fentanyl alone, and a number of lesser known synthetic opioid analogs.
Many exist in a regulatory gray area, and can be ordered wholesale via the internet if you know where to look. Some of these substances are so powerful that the United States has reportedly considered weaponizing them. Other nations already have. In 2002, Russian security forces used a gas believed to be an analog of fentanyl against Chechen terrorists who had taken over a packed theater in Moscow. The compound was so potent that at least 115 hostages also died in the “rescue” attempt.
Quasi-legal derivatives of fentanyl have been used by drug dealers to boost the potency of street heroin since at least the 1970s, when users began overdosing on heroin cut with an analog that medical investigators soon identified as alpha-methylfentanyl. The drug was developed by the same lab that synthesized fentanyl, but has no recognized medical use.
Back then, distribution of alpha-methylfentanyl was limited to California and drug markets in the Northeast—where it mixed easily with the highly refined heroin #4 powder common to those regions. It was frequently marketed under the street names “China White” and “Tango & Cash.”
Alpha-methylfentanyl was made a Schedule I controlled substance in the U.S. in 1981, but it continued to turn up in tainted batches of heroin well into the 1990s, along with an even more potent analog known as 3-methyl-fentanyl (TMF). TMF was outlawed in the U.S. in 1986, but it too surfaced sporadically for many more years.
According to one study, fentanyl-related hospitalizations rose more than 641 percent from 1997 to 2004. Toxicologists were able to identify more than 10 unique fentanyl analogs causing users to get sick during that period. Over the next two years—from April 2005 through March 2007—officials blamed 1,013 deaths in six cities on non-pharmaceutical fentanyl analog. It was the largest NPF epidemic ever reported, according to the CDC.
Since most controlled substances banned under federal law are outlawed based on relatively rudimentary chemical properties, they can be easily altered to circumvent the law. In 1986, this prompted President Ronald Reagan to sign the “Federal Analogue Act,” which outlawed substances that are “substantially similar to the chemical structure of a controlled substance in schedule I or II.”
However, the law left a loophole open for drugs that are “not intended for human consumption.”
Most synthetic opioids finding their way to illicit drug markets are part of a group of compounds known as “research chemicals” (RCs) that are reserved for industrial and medical trials but are largely untested in humans.
Chinese labs are reportedly exploiting that exception to flood the U.S. market with so-called novel narcotics—tweaked versions of existing drugs that fall under the radar of federal law.
While authorities struggle to keep up, a succession of newer fentanyl analogs have found their way onto the street—or “gone wild” as it’s known to the small but active group of RC enthusiasts who discuss experimenting with them in online forums.
“Clever and well-informed drug distribution networks will likely take advantage of the legal loophole and profit by replacing or cutting a highly-regulated drug with this less regulated one,” said John Stogner, a criminologist at the University of North Carolina at Charlotte.
Police are now coming in contact with more illicit fentanyl and other “novel” opioids on the street than ever before. But authorities are unable to keep up with all the legal derivatives.
Last year police in Florida confiscated 2.5 pounds of a powerful, but still legal, synthetic opioid called W-18 during a raid on a suspected fentanyl trafficker. W-18 is said to be 10,000 times stronger than morphine (tests, however have only been conducted on mice); and it is suspected in several recent overdose deaths in Philadelphia.
Another synthetic opioid, U-47700—which was developed by the pharmaceutical manufacturer Upjohn in the 1970s—surfaced in the Dallas area in March. The drug is 7.5-times more powerful than morphine (making it relatively weak in relation to other high-potency synthetics). Yet it’s sent a number of users to the hospital, prompting medical professionals in Texas to issue a public warning.
“We’ve had calls recently from people concerned about this new drug,” said Kristina Domanski, MD, a toxicologist with the North Texas Poison Center. “This seems to be a pretty new recycling of the drug which is intended as a research drug and not for use in humans.”
Sweden and Finland have passed laws making U-47700 illegal, and last month Ohio Governor John Kasich added it to the state’s list of scheduled substances (PDF). But there are currently no federal guidelines banning its sale in the U.S.
In 2015, a little-known analog known as acetylfentanyl was banned by the DEA two years after it first showed up in tablets tested in Maine. Two others fentanyl analogs—butyryl-fentanyl and beta-hydroxythiofentanyl—were subjected to emergency scheduling by the DEA only last month (PDF). On May 16, the DEA also emergency scheduled a relatively weak synthetic opioid known as AH-7921 after catching wind that it was gaining interest among drug enthusiasts in online chat rooms.
By that time, however, a legal replacement known as furanyl-fentanyl was already making headlines. Since the beginning of the year furanyl-fentanyl has been blamed for 10 overdose deaths in Pennsylvania and recently sent two North Dakota high school students to the emergency room.
One Chinese lab, which says it specializes in the sale of research chemicals, lists a gram of furanyl-fentanyl for $80.
In May, Sen. Pat Toomey of Pennsylvania, which ranks third in the nation in fentanyl seizures, penned a letter to Secretary of State John Kerry urging the Obama administration to put pressure on China to “immediately stop the export of illicit fentanyl and dangerous analogues.”
“Limiting the introduction of synthetic fentanyl and related analogues will help save lives and give those battling addiction another opportunity at recovery,” Toomey stated. In his remarks he singled out “domestically unregulated” furanyl-fentanyl as a particular cause of concern.
In Philadelphia, where fentanyl-laced heroin has been blamed for periodic increases in drug fatalities for decades, fentanyl-related deaths spiked at the beginning of 2014 and continue to rise (PDF). Sources told The Daily Beast that dealers are, for the first time, openly marketing the drug for sale at half the price of a typical $10 baggie of heroin. (Users report a “good rush” but complain about fentanyl’s “short legs”—a reference to its limited window of effectiveness as compared to heroin.)
As the crackdown on prescription opioids pushes more users from the doctor’s office to the street, distributors will be drawn to new and powerful opioid substitutes with little concern for where they come from.
And therein lies a conundrum: Limiting diversion of powerful painkillers from regulated pharmaceutical channels creates new unregulated avenues for satisfying demand. In most cases these secondary avenues are more dangerous than the original ones we are trying to shut down. It’s a glaring oversight for a country that otherwise reveres the autonomous power of the “invisible hand” of the free market.
In response to China’s recent export ban of 116 research chemicals, one online poster to a research chemical forum summed up: “If there’s demand, it will be produced—legally or not. Worst thing is that from now on our stuff will come from catchy backyard labs without quality control. People will die. Way to go prohibition.”