an alternative to morphine, the reigning pain reliever of its time.
Derived naturally from the resin of the opium poppy, morphine was chemically isolated at the dawn of the nineteenth century by German pharmacist Friedrich Sertürner, who named it for Morpheus, the Greek god of dreams. Janssen tested the effectiveness of fentanyl on lab mice, placing the mice on hot plates and slowly turning up the heat to gauge their reactions.
Fentanyl was particularly profitable for Janssen Pharmaceutica. Doctors found it superior to morphine because of the way it acted. Like morphine, it bound with a receptor in the brain (which we now call the “mu” receptor) to cause pain relief. But fentanyl came on faster, was much more powerful, and wasn’t as likely to cause nausea. “Fentanyl,” Janssen later wrote, “made it possible for the first time to perform lengthy operations and, together with its successors, heralded a revolution in the operating theatre. Without this compound and its analogue, sufentanil, open-heart surgery [as performed today] would not be possible.”
The drug was a revelation, and it went on to become the world’s most widely used anesthetic. Janssen Pharmaceutica was purchased by American behemoth Johnson & Johnson in 1961, and Paul Janssen continued working for the company, tasked with developing other types of fentanyl, referred to as analogues. But almost from the start, fentanyl’s potential addictive dangers were recognized, and it was placed under international control by a United Nations agreement in 1964. This led countries including the United States and the United Kingdom, in 1971, to schedule it—that is, to ban its recreational use. Indeed, its euphoric qualities would prove too much for many users to resist. “Fentanyl is a good medicine but a bad drug,” Justice Tettey, chief of the Laboratory and Scientific Section at the United Nations Office on Drugs and Crime, summed up later. “It has excellent pain relieving properties, but is liable to abuse and can rapidly lead to dependency.”
Despite fentanyl’s quick success as a painkiller in Europe, during the 1960s it was almost blocked for sale in the United States by the Food and Drug Administration. One vocal opponent to the drug’s approval was University of Pennsylvania anesthesiology professor Robert Dripps. A rare outlier who believed fentanyl’s high potency could lead to abuse, he eventually agreed to a compromise after being lobbied by Paul Janssen himself: fentanyl would be available, but only when diluted with another drug called droperidol, a sedative—also patented by Janssen—that was believed to mitigate fentanyl’s detrimental effects. A ratio of fifty parts droperidol to one part fentanyl produced a “bad high” when taken recreationally, Dripps and Janssen agreed, and thus was unlikely to be abused. The FDA approved this combination in 1968. Fentanyl’s success boosted Janssen’s bottom line, which drove Paul Janssen and his colleagues to develop many other fentanyl analogues. Some, like alpha-methylfentanyl, were never turned into medicines that were sold. Others, however, made it to market, including sufentanil, used in long-lasting surgeries, and carfentanil, a veterinary medicine that is the strongest fentanyl analogue ever made commercially.
At the very end of the 1970s, a pair of overdose deaths in Orange County, California, stumped authorities. A few bits of information were known about the victims. They seemed likely to have both used heroin, as shown by their telltale scarring (tracks) and the heroin paraphernalia discovered with their bodies. But toxicology reports bizarrely didn’t turn up any known drugs in their system. Soon, a half dozen more people in the county had died under similar circumstances, and then twice as many.
Around the same time, police began discovering a new drug on the street, China White. Traditionally, dealers of China White touted their product as the finest heroin available—pale in color and originating in East or Southeast Asia. “To get connected with China White is a sort of fantasy for [opiate] addicts,” Darryl Inaba, director of the Haight-Ashbury Free Clinic of San Francisco, said in a report in US Navy Medicine. This new China White had no heroin in it, however, and rather than a fantasy it was a nightmare. Instead of pure heroin from Asia, laboratory analysis determined that it contained something called alpha-methylfentanyl—a fentanyl analogue.
Though this particular chemical had been synthesized by Janssen Pharmaceutica, it was never developed into a medical product. The source of the China White remained a mystery. Presumably, the recipe had been stolen from scientific literature published by Janssen scientists, and then the drug had been cooked up by rogue chemists. But no China White lab was ever seized, and no one was arrested. There were plenty of guesses, however, including some wild speculation from a famed psychedelic chemist and drug expert named Alexander “Sasha” Shulgin. “Had China been developing some super-potent fentanyl analogues as potential warfare agents? Let the fantasy roll,” he wrote in 1997. “Maybe the Chinese were using second class citizens (the drug-using population of California) as guinea pigs for the initial human trials of their new drugs.” Also suspected were scientists in Russia, which had developed fentanyl problems of its own.
China White represented a fish-crawling-onto-land moment: it was the first popular, illicit drug synthesized by a rogue chemist that was new, rather than simply a copy of something already on the medical market. And thus, alpha-methylfentanyl was the first in a long line of new psychoactive substances that came to include K2, Spice, “bath salts,” and all the other substances this book is about. Back before they were called novel psychoactive substances, or NPS, they were known by another name: designer drugs.
Calling alpha-methylfentanyl China White was smart marketing, as it evoked a desirable type of heroin. What truly helped the product stand apart, however, was the fact that it was legal. Fentanyl itself had been illegal for recreational use since 1971, as a schedule II drug.** And chemically alpha-methylfentanyl was almost identical. But the key word is almost. It wasn’t identical. It had a unique molecular design. And therefore the police were powerless. “You could walk around with a shopping bag full of it and nobody could do anything to you,” observed Robert J. Roberton, chief of the state of California’s Division of Drug Programs.
Other fentanyl variations followed on alpha-methylfentanyl’s heels. In the early 1980s, more troubling reports about users injecting drugs that weren’t quite heroin emerged from California. In 1982 a man named George Carillo was brought to a San José hospital practically immobile, and his girlfriend, Juanita Lopez, came in a week later, also suffering from stiffness, paralysis, and other symptoms similar to Parkinson’s, except Carillo and Lopez were too young to have the disease. A handful of other victims with similar symptoms were soon identified. Eventually their condition was traced back to a new opioid they had injected called MPPP, which was intended to imitate heroin but had been synthesized incorrectly, inadvertently creating a different substance, MPTP, with disastrous side effects. This story at least has a silver lining, as research on the victims catalyzed new discoveries leading to advancement in Parkinson’s research.
It took the DEA six months to schedule a new drug, and by that time new analogues were already popular on the streets. So in 1984 Congress granted the DEA emergency scheduling powers, so the agency could ban drugs immediately. But even this was insufficient to stop the new fentanyl analogues, which sometimes started killing people before the DEA had even heard of them.
And so the US government began regulating drugs that didn’t yet exist. The Federal Analogue Act was signed into law by President Ronald Reagan in 1986. The legislation specifically went after fentanyls and what would become known as designer drugs and NPS. It made anything deemed “substantially similar” to schedule I or II psychoactive drugs—in either effect or structure—automatically illegal the moment it came into being.
However, banning something “substantially similar” proved challenging. Just because chemicals have similar structures doesn’t mean they will affect the human body the same way; in fact, quite often the effects can be dramatically different. Further, the law aimed at psychoactive substances, but what constitutes psychoactive can be debated. A strong cup of coffee can have a powerful impact, as can large amounts of chocolate and sugar.***
The US Federal Analogue Act is still used to prosecute makers of analogue drugs, yet little evidence
