COLUMBUS, OHIO — A new generation of homemade synthetic drugs is reshaping America's overdose crisis, public health workers and law enforcement say, as fentanyl is increasingly cut with animal tranquilizers and obscure lab-made opioids that even the overdose-reversal drug naloxone cannot touch.
The shift was documented in detail by the BBC, which spent days with users, dealers and recovery workers in Ohio and Illinois. Fentanyl, 50 to 100 times more powerful than heroin, is now routinely mixed with xylazine and medetomidine, veterinary sedatives that prolong its high but do not respond to naloxone, the nasal spray credited with reversing tens of thousands of opioid overdoses nationwide. Xylazine use also causes deep, necrotic skin ulcers that are difficult to treat.
These adulterants, along with newer synthetic opioids known as nitazenes, are increasingly produced in small domestic labs rather than imported wholesale — cocktails that can be mixed in American basements and bathtubs, complicating efforts to track and intercept the supply.
Deaths falling, but not evenly
The crisis comes even as the national overdose death toll keeps falling. Provisional data released by the Centers for Disease Control and Prevention show an estimated 69,973 Americans died of drug overdoses in 2025, down nearly 14% from 81,313 in 2024 and well below the 2022 peak of roughly 110,000 deaths. Opioid-involved deaths fell to about 44,500 from more than 55,000 a year earlier.
But the decline has been uneven, and the new synthetic compounds are straining detection and treatment systems built around fentanyl alone. At Cook County Jail in Chicago, one of the largest in the country, officials said synthetic cannabinoids soaked into paper mail caused a cluster of fatal seizures, prompting the jail to begin scanning all incoming letters for moisture; officials said between a fifth and a quarter of mail now tests positive and is rejected. Recovery groups in Columbus and Chicago, including the Illinois harm-reduction group Liv4Lali, say they are now distributing test strips that screen for fentanyl, xylazine, medetomidine and other adulterants, after finding that users who believed they were smoking fentanyl alone were often unknowingly taking far more.
Recovery workers describe a population still being left behind by the broader national improvement. Overdose deaths among Black men in Ohio are rising even as the state's overall numbers fall, said Scott Sanders, who runs the Hope Dealers recovery group in Columbus and works with the CDC on a drug-sampling program that tests users' paraphernalia for contaminants.
Officials say there is no sign the underlying supply chains, run largely by Mexican cartels moving precursor chemicals from China, have been disrupted despite stepped-up enforcement, including the designation of cartels as terrorist organizations and military strikes on suspected trafficking boats. Treatment providers say the next phase of the fight will depend less on interdiction than on expanding access to fentanyl test strips, naloxone and the kind of community-based recovery programs now trying to keep pace with a drug supply that keeps changing faster than the response to it.
