The Rise (and Rise) of Fentanyl

Most new drugs that shake up illegal markets strike with apparently little warning. Pharmaceutical companies, in contrast, go through years of development and multiple trials before releasing a drug; illegal markets bring new products seemingly out of nowhere. Crack arrived as a shock in the early 1980s, as did methamphetamine in the 1990s. Both arrived as altered forms of previously known drugs, but the speed or ferocity with which they dominated illegal markets caught health professionals, policymakers and law enforcement by surprise. 

Some prescient observers had been forecasting that synthetic drugs could take over from plant-based drugs. That reflected a belief that modern chemistry could produce more interesting psychostimulants closer to the customer base and with a more controllable production cycle because, for example, it would not be dependent on a growing season. However, it was a broad and vague prediction, unhelpful for policymakers. Yet the arrival of illegally manufactured fentanyl (IMF) in 2014 was a shock, even though or perhaps because there had been a few short-lived episodes of it popping up. Furthermore, fentanyl patches had been a staple anesthetic in the United States for over 40 years, with some diversion and misuse resulting in about 2,000 to 3,000 fatal overdoses annually, a small share of all overdose fatalities.

Even to jaded students of drug history, the ferocity with which fentanyl overtook the narcotic market since its first true appearance in around 2014 has been stunning. Multiple factors drove the appearance of cheap and plentiful IMF, including the dissemination on the internet of new, simpler methods of synthesizing the drug that had been developed in India and published as a “one-pot” method for synthesis in 2005. Fentanyl is roughly 25 times more powerful than heroin per unit weight; about 2 milligrams of pure fentanyl is the standard quantity in counterfeit tablets today. To get a sense of how minute that is, note that an ounce is 28,350 milligrams; a fentanyl dose is less than one ten-thousandth of an ounce.

The drug has caused a doubling of fatal overdoses nationally in just seven years, to a total in 2021 of over 100,000 in the U.S. More than 70,000 of these deaths involve synthetic opioids, the vast majority of which are fentanyl. 

What is unique about fentanyl compared to other new illegal drugs is that its spread was not driven by demand. For example, crack was an exciting, fast-acting form of cocaine that was sold in smaller, more affordable units. It was used in different ways. And it gave a shorter, more intense high than did insufflating powder cocaine.

By contrast, fentanyl’s original appeal was to the drug traffickers, who found it attractive to mix cheaply with expensive heroin. Later, many left out the heroin and just sold fentanyl. Some customers liked the new drug; most didn’t. None initially even knew they were consuming fentanyl or asked for it by name. Over time in some markets, customers became used to fentanyl, and, as my food scientist father used to say, “Good is what you’re used to.” These markets largely became fentanyl-only markets; heroin has essentially disappeared in cities such as Boston and Philadelphia.

For the first five years, 2014-2018, small players associated with the chemical/pharmaceutical industry in China appear to have had an important role in the supply of fentanyl, advertising it for sale on the web. The offer was to deliver as much as a kilogram of very pure fentanyl to an address anywhere in the U.S. for about $5,000, which is about a penny per dose. Delivery was by parcel post or express courier. Under pressure from the U.S. government, China in 2019 passed new legislation prohibiting the manufacture and marketing of fentanyl and fentanyl analogs. U.S. seizures of fentanyl in the postal and parcel system fell sharply. 

Today, IMF is largely processed in Mexico, using precursor chemicals that are often exported from China. Though it is no longer as widely available on the web, the wholesale price of fentanyl inside the United States has been falling, and for users, it remains much cheaper than heroin per dose.

The early diffusion of IMF showed striking and puzzling regional differences. It first appeared in parts of New England and Appalachia as well as in British Columbia, Canada. For the next five years, the great mystery was not why fentanyl dominated illegal opioid markets in those places, but why there were so many cities west of the Mississippi where it remained rare. 

Heroin was still the dominant drug in the West five years after Ohio and New Hampshire had already been flooded with fentanyl, adding to the damage caused by prescription opioids. The fatal overdose figures showed dramatic regional disparities in those first five years. in 2019 in Ohio there were 38 drug ODs per 100,000 residents, mostly fentanyl-related, while in Washington State the rate was only 16 per 100,000, with minimal fentanyl involvement. 

It is hardly possible that West Coast heroin dealers were unaware of the attractions of fentanyl. The notion that they were more concerned than East Coast dealers with the well-being of their customers is hard to state with a straight face. And indeed, fentanyl has now reached the West Coast. In 2022, Washington State had almost caught up with Ohio of 2019 (36 OD deaths per 100,000) but Ohio has continued to surge, to 48 OD deaths per 100,000. 

The uneven distribution in the United States and Canada is wrapped in a larger mystery: Why has illegally manufactured fentanyl not spread beyond North America? Countries with substantial and long-standing heroin markets, such as Australia and the United Kingdom, are also well connected in commerce and traffic with China, the source of the drug. Yet almost a decade after IMF entered the U.S. and Canada in quantity, it still remains a fringe contributor to opioid markets outside of North America.

It is tempting, as always, to blame a wretched drug problem on this nation’s much-excoriated drug policy. However, that temptation is easy to resist here. Canada is also badly affected. The problem is particularly severe in harm-reduction-oriented British Columbia, where the fentanyl problem is about as bad as in the worst states in our own country. Fatal overdoses in the first seven months of 2023 suggest that British Columbia is heading to a new record number, far exceeding the 44 per 100,000 of 2021. A prominent study estimated that the OD rate would have been twice as high without its interventions such as drug consumption rooms, hydromorphone dispensing, syringe exchange and accessible treatment services. 

There are good arguments for all of these interventions, but they are clearly not enough to prevent a massive problem, or at least not without a huge expansion. Nor does the much more supportive social policy of Canada that keeps its poverty rate lower than in the United States, as well as provide ready access to health care, prevent this disaster.

The future is bleak. A Lancet Commission projected a total of 1.1 million fatal opioid-related overdoses in the 2020s in the United States without major changes to policy. That reflects a recent study of drug fatalities in this country over a 45-year period. There has been a remarkably consistent 7% annual rise in drug overdoses since 1978, leading to a doubling every 10 years. One could bleakly say that the introduction of fentanyl was just God’s way of keeping us on the curve. There is no reason to think that the peak of this problem is in sight, even with the Sinaloa Cartel, the principal manufacturer, claiming to have eliminated fentanyl production in its territory in the Mexican state of Sinaloa. New York City, already badly hit in 2019 with 1497 drug deaths, saw a doubling over the next three years; of its 3,026 fatal overdoses in 2022, 81% involved fentanyl. 

Fentanyl is a particularly difficult target for supply control efforts, which have not even done well against cocaine, heroin or methamphetamine. Its high potency means that the quantity of pure fentanyl that needs to be smuggled into the United States is tiny, probably less than 10 tons. Surprisingly, the smuggling target is a lot larger than that because so much is imported in the form of pills; the fentanyl in the pill is typically just 2% of the total weight. However, production is cheap and completely flexible. No need to worry about droughts or floods or government spraying of poppy fields; just ask one of the labs to run a few more batches after a big seizure at the border. There are a few clever ideas for reducing drug-related violence in Mexico, but none offer a realistic prospect of reducing exports to the United States. 

Every drug epidemic in the past has run its course. The rise in new users turns down rapidly as the bad effects of the use of the drug become prominent. 

Fentanyl is wreaking its havoc largely among those who were already using illegal drugs but also in those who mistake counterfeit tablets for prescription opioids. The death rates amongst those who use opioids and stimulants are high enough that the population of individuals dependent on these drugs may now be declining.

Thus, the downturn in fatalities, when it comes, may reflect not a decline in the popularity of fentanyl but just the falling numbers who are exposed to its effects. This will be good news wrapped in awful news. Expanding treatment and harm reduction services in quality, quantity and accessibility is perhaps all that can be done at this stage. Alas, expectations of success in significantly reducing the death toll in the near future should be low.