Fentanyl has been around since the late 1950s, when it was first synthesized in a Belgian laboratory. It received FDA approval for medical use in the United States in 1968, meaning it has been part of clinical medicine for well over half a century. But the drug’s role in society has shifted dramatically over that time, from a tightly controlled surgical painkiller to the single deadliest driver of overdose deaths in the country.
How Fentanyl Was Created
Fentanyl was developed by Dr. Paul Janssen, founder of Janssen Pharmaceutica (now a division of Johnson & Johnson), in Beerse, Belgium. In the late 1950s, Janssen’s team set out to create stronger painkillers for conditions that existing drugs couldn’t adequately treat. Over three to four years, they synthesized and tested a series of new molecules in animal models. The best-performing compound became fentanyl.
What made fentanyl stand out was its extraordinary potency. It is roughly 100 times more potent than morphine and about 50 times more potent than heroin. That potency made it useful in very small, precisely measured doses for surgical anesthesia, where doctors needed a fast-acting painkiller they could tightly control.
FDA Approval and Medical Use
The FDA first approved fentanyl in 1968 under the brand name Sublimaze, an injectable form used primarily during and after surgery. For decades, fentanyl remained mostly a hospital drug, administered by anesthesiologists in operating rooms and intensive care units. Its rapid onset and short duration made it ideal for procedures where pain control needed to be switched on and off quickly.
Over the following decades, new delivery methods expanded its use beyond the operating room. Transdermal patches (the familiar slow-release skin patches) arrived in the early 1990s, allowing fentanyl to treat chronic pain in patients who needed round-the-clock relief, particularly cancer patients. Lozenges and other formulations followed. Throughout this period, fentanyl was considered a specialist drug, prescribed primarily by pain management doctors and oncologists rather than general practitioners.
Fentanyl Analogues
Janssen’s laboratory didn’t stop at fentanyl. The same research program produced a family of related compounds over the next two decades. Carfentanil, discovered in 1974 and approved for veterinary use in 1986, is roughly 10,000 times more potent than morphine and was designed to sedate large animals like elephants. Sufentanil, remifentanil, and several others were developed for specialized roles in human surgery and animal medicine.
These analogues matter today because their chemical blueprints are publicly known, and clandestine labs have used them to produce a rotating menu of synthetic opioids that are difficult for law enforcement to track and extremely dangerous in uncontrolled doses.
The Shift to Illicit Manufacturing
For roughly 45 years after its invention, fentanyl’s presence in the illegal drug supply was minimal. That changed around 2013, which the CDC identifies as the start of the “third wave” of the U.S. opioid epidemic. The first wave, beginning in the 1990s, was driven by prescription opioid pills. The second, starting around 2010, was driven by heroin. The third wave brought illegally manufactured fentanyl, often called IMF, into the picture on a massive scale.
Between 2013 and 2014, fentanyl-related law enforcement submissions surged across 27 states, and overdose deaths involving synthetic opioids climbed sharply. Unlike diverted pharmaceutical fentanyl, the illicit supply was being produced in overseas labs (primarily in China initially, then increasingly in Mexico) using precursor chemicals. The drug was cheap to make, incredibly potent in tiny quantities, and easy to smuggle. Dealers began mixing it into heroin, pressing it into counterfeit prescription pills, and eventually lacing it into stimulants like cocaine and methamphetamine.
Where Things Stand Now
Fentanyl remains the dominant synthetic opioid in the U.S. illegal drug supply. In 2024, the DEA seized 9,950 kilograms of fentanyl powder and 61.1 million counterfeit pills containing fentanyl. When you include seizures from all federal, state, and local agencies, the total reached 23,256 kilograms for the year. The vast majority entered through the Southwest Border, with 14,069 kilograms seized there alone, most of it at the Arizona-Mexico crossing. By comparison, just 22.7 kilograms of fentanyl were seized at the U.S.-Canada border in the same period.
Those 2024 numbers actually represent a roughly 25 to 29 percent decrease from 2023, though it’s unclear how much of that reflects reduced supply versus shifts in trafficking patterns. Either way, the scale remains enormous. A single kilogram of fentanyl can theoretically produce hundreds of thousands of doses at street-level potency.
So while fentanyl has existed for nearly 70 years, the version of it that dominates headlines today bears little resemblance to the carefully dosed surgical tool Paul Janssen’s team created in Belgium. The molecule is the same, but the context has changed entirely: from sterile hospital vials measured in micrograms to bulk powder pressed into pills that users often don’t even know contain fentanyl.