Dark Innovation: Fentanyl’s Children

What has been used in surgery, anesthesia, and pain management since the 1960s emerged in the late 1970s as a major recreational drug, encountered and abused with destructive results, and plagues the United States today.

“Fentanyl is a good medicine but a bad drug.”

Laboratory & Section Chief, UN Office on Drugs & Crime
(Ben Westhoff, Fentanyl, Inc., p. 34)

FENTANYL and its analogues have benefited patients in operating rooms and in the management of pain. For decades they were the focus of the kind of innovation that makes America a leader in solving problems in a variety of areas – in this case, medical chemistry and surgery.

1911-1973

Despite bona fide benefits, anesthesiologist Dr. Robert D. Dripps (left) of the University of Pennsylvania Medical School had warned (see previous column) in the mid-1960s of the room for abuse of these powerful substances and the potential of certain chickens coming home to roost.

As early as 1961, many in fact recognized the addictive dangers of laboratory fentanyl and its analogue “progeny,” and the United Nations coordinated the signing of a “Single Convention on Narcotic Drugs” with things like meperidine/Demerol put on established “Schedules” (I-IV) that exist today to ban them from recreational use. Various drug treaties followed such as in 1971 and 1988. In 1986, Congress passed the Federal Analogue Act to head off a dangerous late 1970s trend – of fentanyl being changed into different forms and distributed outside legal medical channels.

At this time, we see the constructive revolution of the 1960s/1970s that used fentanyl to advance medicine now joined by another – destructive – revolution, this time a dark one.

Something called “China White” (photo nearby) began appearing in places such as the neighborhoods of Los Angeles and Orange County. It originated somewhere in East or Southeast Asia, and was touted the finest heroin available. The demand among addicts was high, but China White attracted attention not only for its purity but because overdose deaths came in unexplained numbers, confusing law enforcement. The problem was that this “finest heroin” had no heroin. It contained something new; called alpha-methylfentanyl – the first fentanyl analogue to appear on the street, and one infinitely stronger than the heroin addicts thought they had bought and mainlined.

Here was a hinge moment, a watershed around 1980 because “China White” was the first in a line of substances called novel psychoactive substances (NPS), or more simply, “designer drugs.” These were what the Reagan Administration’s Analogue Act was trying to control in 1986: new sinister substances growing up to replace LSD, ecstasy, marijuana, and even heroin; totally synthetic substances that grew out of legitimate efforts to control pain in the 1960s and 1970s and saw the rise of prescription and legal oxycontin and hydrocodone (Vicodin).

Opium Poppy Field: Helmand Province, Afghanistan

China White is worth mentioning because it indicated a new pattern: a solitary chemist making several grams of a new substance – thousands of doses worth a ton of money – and then shutting up his shop. Besides his illusiveness, these new fentanyl-based substances retained all the psychoactive properties of a drug, but a molecular structure that had been altered just bit to avoid prosecution since the drugs were not “scheduled.”

And the compounds were completely synthetic. No more worries about poppy crops going bad half a world away, or wars interfering with trade routes. In fact, the very success to curtail plant products from far away places like Afghanistan and Myanmar (including even the derivative heroin) only stimulated the development of potent synthetic substitutes, manufactured in by our rogue chemists in the United States or overseas in attics, basements, garages, or living rooms.

It has been illegal to manufacture, distribute, or possess fentanyl analogues since 2018. Now there exists, though, a cat and mouse game between legislators / law enforcement and chemists who develop new products related to fentanyl, of which the Drug Enforcement Administration lists about 1400 . . .

. . . and counting. A drop in the proverbial bucket might include:

• acetylalphamethylfentanyl
• acrylfentanyl
• alfentanil
• allylfentanyl
• alphamethylfentanil (“China White”)
• alphamethlthiofentanyl
• benzodioxolefentanyl
• betahydroxyfentanyl

• betahydroxy-3-methylfentanyl
• butyrfentanyl
• carfentanil
• crotonyfentanyl
• cyclopentyfentanyl
• difluorofentanyl
• FENTANYL (1960)
• fluorofentanyl
• fluorobutyrylfentanyl
• furanylfentanyl
• isobutyryfentanyl
• isofentanyl
• lofentanyl
• methoxybutyrfentanyl
• methoxycarbonylfentanyl
• methylbutyrfentanyl

• 3-methylfentanyl
• 3-methylthiofentanyl
• octfentanil
• orthofluorofentanyl
• parafluorofentanyl
• phenylpropanoylfentanyl
• remifentanil
• sufentanil
• tetrahydrofuranylfentanyl
• tetramethylcycloproylfentanyl
• thiafentanil
• thiofentanil
• trefentanil
• valerylfentanyl

This very small sample of current illegal analogues blossomed quickly from the late 1970s onwards, and was kind of a dark wave of innovation following the innovations of the 1960s and 1970s of constructive medical progress. It happened under the radar while the main event seemed to be an epidemic of non-fentanyl prescription narcotics – more powerful than morphine such as OxyContin and hydrocodone – that raged across the United States and world and grabbed headlines in the late 1990s and early 2000s.

Around 2010, the overprescription problem was joined by a second opioid problem trend – that of a great rise in heroin use and accompanying overdose deaths.

Narcotic overprescriptions and heroin began to level off in 2016, but were replaced by a kind of “third horseman” combining the first two together and making the situation worse than either of the other two standing alone. The third “horseman” burst into public consciousness in the form of fentanyl and its powerful analogues “cut” into heroin in minute amounts as well as mixed into legitimate tablets of what appeared to be, for example, Oxy, hydrocodone, Percocet, or even drugs like Xanax. Chemists in small labs and the rise of home-based pill presses producing thousands of street tablets per day created a supply of street drugs that sometimes advertised as one thing such as high grade heroin or Percocet, but contained unknown fentanyl analogues that killed an unsuspecting person.

CDC figures showed overdose deaths increasing from 2014, and point to the important year of 2016 as the year when fentanyl broke into public consciousness as a word and as a problem. Death rates from all synthetic opioids increased 72% from 2014-2015. Bad as this was, deaths the following year really grabbed attention with a 540% jump. Here in 2016 was a staggering acceleration and a trend; here was the death of the singer Prince, here was a national political issue that had occupied the Obama administration before 2016 but became an emergency for candidates in 2016 and for Presidents Trump and Biden thereafter (as the inflection point on the nearby graph indicates).

Big Deal CHINA-MEXICO Issue

Illicit Synthetic Opioid Flows from China (Photo: GAO, 2019)

Until 2018, most Fentanyl and its progeny entered the US from China through the Post Office and International Express mail. Specifically, China was the source of 97% of inbound shipments of the highest-purity fentanyl (DEA, “2018 Drug Threat Assessment,” Oct. 2018). Most recently, though, more and more package mail seizures have made smugglers shift this traffic away from the mail per se, and down to the southern border – in a tremendous way.  In 2019, Customs and Border Protection agents have seized more than 2,000 pounds of fentanyl – easily enough to poison the entire American population.

And China remains the center of attention on the fentanyl issue, regardless of entry point to the United States, and regardless of its assuring the G-20 nations it has banned all fentanyl analogues as of 2019. From a recent account:

Many of the NPS killing Americans Europeans, and others are still 100 percent legal in China, even while banned in the West. In recent years some of the biggest drug kingpins can’t be prosecuted. The Pablo Escobars of today are coming out of China, and they don’t have to worry about being imprisoned by their government. They can operate free and in the clear, within the boundaries of their own laws (Westhoff, Fentanyl, Inc , p. 23).

One of the “trade” issues that the Trump administration had with China was its exportation of the lion’s share of illicit fentanyl to the United States and around the world.

So in addition to American rogue chemists manipulating their own fentanyl molecules, we have the problem of the importation of Chinese-manufactured fentanyl, getting into the country by – yes, the southern border of the United States. From here, it is inserted / mixed into all sorts of pills from OxyContin (“M-30s” at left) to Tylenol to Xanax. It is marketed in the Dark Web, and exchanged by various cryptocurrencies – all with deadly results.

And thus, the 1960s collides vividly with pressing contemporary American politics in the form of border security since it is the Mexican cartels, violent and fabulously wealthy, that often ferry a product – first produced in 1960 – into the United States by any means possible, and with astronomical profits.

The antipathy of Americans toward the Mexican cartel gangs is clear, particularly the border states of Texas, Arizona, and New Mexico. What is newer is the rigid stand against China under the Trump administration. “We need to make very clear to the Chinese,” said Trump spokesman and former NJ governor Chris Christie, “that this [manufacture and smuggling] is an act of war. You are sending [fentanyl] into our country to kill our people.”

Trump was decisive on this issue, and built 400 miles of border wall to, in part, mitigate this grave and poisonous threat of a product first produced in 1960. The Biden administration’s approach has yet to fully emerge.

Ending this short piece, it’s good to mention that the substance called fentanyl causing overdose deaths across the world in ever-increasing numbers was indeed a product of the 1960s.  But so was its antidote. In 1961 a compound called naloxone emerged which reverses the effects of fentanyl and revives overdosed victims on the verge of death. Naloxone is used hundreds of times daily across the United States to save lives. The 1960s created a problem, then kind of tried to solve it. Kind of putting a genie back in a bottle.

Fighting Fentanyl: carried by every EMT today.

I know it sounds odd, but I’d like to include a fun postscript on fentanyl next time.  Fentanyl, fun!!?  Yup.

POSTSCRIPT
Fentanyl, Flying Syringes, and a TV Show

Until next month,
PEA
peterevansaustin@gmail.com
March 12, 2021