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The opioid crisis that grips the United States has a central chemical villain: fentanyl. The synthetic drug, deadly even in the tiniest doses, flows into the country and is mixed with other narcotics, such as heroin and cocaine, and is sometimes pressed into pills that masquerade as prescription painkillers. In 2022, more than 73,000 people died from fentanyl overdoses in the U.S. alone, according to data from the Centers for Disease Control and Prevention.
The primary ingredient in fentanyl is piperidine, a ring-shaped organic molecule that sits in the center of a compound that includes three other components: an aniline ring, an alkyl chain, and an acyl group. Andrea Holmes, a chemist at Doane University in Nebraska, told Reuters last year that the chemical structure of fentanyl is best imagined as a Mr. Potato Head toy—piperidein is the head while the other three compounds make up the eyes, nose, and mouth.
Piperidine is used in the manufacture of many other pharmaceuticals, but the U.S. government has placed the toughest restrictions on precursors of fentanyl, which all have piperidine at their core, that make it relatively simple to synthesize the deadly drug. These include 4-anilino-N-phenethylpiperidine (4-ANPP), N-Phenethyl-4-piperidone (NPP), 4-Aminopyridine (4-AP), and norfentanyl, each just a simple chemical tweak away from becoming fentanyl.
Read more: “Painkillers That Don’t Kill”
According to a 2020 report from the U.S. Drug Enforcement Administration, China is the main source of fentanyl and fentanyl-related products that end up in the U.S. That latter class includes chemical precursors of the drug, which make their way to Mexico, where cartels oversee the manufacture and export of fentanyl.
Exporters can and do alter the chemical makeup of these precursors to mask their identity, making it extremely difficult to track and stem their flow across borders, and potentially leading to fentanyl analogs—such as the elephant tranquilizer carfentanil—that can be 100 times more potent than fentanyl.
The lethal game of cat and mouse between drug exporters and manufacturers and authorities shows no signs of slowing, but fentanyl deaths did dip in 2023 and 2024, according to provisional data from the CDC.
As authorities seek to slow the damage that fentanyl is causing in the U.S. and beyond, they must keep an eye on an entire spectrum of chemicals, from the finished product to all the components that make it up. 
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Lead image: United States Drug Enforcement Administration (DEA) / Wikimedia Commons
