The U.S. opioid crisis has not ended even as overdose deaths have fallen. Drug overdose deaths reached roughly 110,000 in 2022 before dropping to about 70,000 last year. But fentanyl is increasingly being mixed with animal sedatives, stimulants and other chemicals made in illicit laboratories, changing both the drug supply and the way overdoses present.
In Columbus, Ohio's Linden neighborhood, 48-year-old veteran Mike continues to use fentanyl. He has a 20-year history of opioid use and supports himself with temporary jobs at pawn shops and gas stations. He said a small amount of the drug costs about $3 to $4, but once an overdose is inhaled, there is no taking it back — like "a bullet after it has been fired."
Fentanyl is entirely synthetic and is estimated to be 50 to 100 times more potent than heroin. Street samples now frequently contain other synthetic sedatives, making users harder to wake and emergency treatment less predictable.
Naloxone cannot reverse every component
Naloxone nasal spray, widely used in the United States, can quickly reverse an opioid overdose and has helped save many lives. But the sample Mike used may have contained more than fentanyl. His pupils were unusually constricted, and he later said the drug may have contained xylazine and another difficult-to-pronounce substance: medetomidine.
Xylazine and medetomidine are both synthetic veterinary sedatives. They can prolong fentanyl's effects while suppressing breathing, but naloxone does not directly counteract either sedative. Xylazine can also cause necrotic skin ulcers. In severe cases, wounds can extend to the bone and require lengthy treatment.
At Glenwood Church in Columbus, the recovery group Hope Dealer Community holds weekly meetings. Members share experiences of overdoses, withdrawal and losing relatives. One man recalled overdosing in July 2022. Emergency responders administered naloxone three times without success before a final attempt revived him.
Another member, Tonya, described the death of her nephew from an overdose. At the same time, she was overdosing herself after using cocaine contaminated with fentanyl. She said surviving was not a given.
Stimulant users face growing exposure
Scott Sanders, head of Hope Dealer Community, said stimulants were involved in 78% of fatal overdoses in Franklin County, where Columbus is located, during the past 12 months. Some users believe they are buying cocaine or another stimulant but receive a product mixed with fentanyl or other opioids, leading to an overdose without their knowledge.
The group works with the U.S. Centers for Disease Control and Prevention on drug sampling. Participants can submit swabs from needles or pipes, and the samples are sent to a laboratory in North Carolina. One of the samples Mike brought tested positive for medetomidine, supporting his suspicion about the drug's contents.
Sanders said the street supply in 2026 is no longer simply a matter of traditional adulteration. Multiple substances are being blended directly, including fentanyl, methamphetamine and other chemicals produced in illicit settings. He also said overdose deaths among Black men in Ohio are still increasing.
Soaked paper emerges in Chicago jail
The changing synthetic-drug supply is also appearing in the prison system. Cook County Jail in Chicago averages one or two overdose deaths a year, but eight detainees died from fatal seizures in 2023.
Cook County Sheriff Tom Dart said surveillance footage showed some detainees setting paper on fire in microwave ovens in the jail's cell kitchens. Investigators found that drugs had been soaked into book pages and letters, then inhaled when the paper was burned. The substances included the fully synthetic cannabinoid product K2, which was linked to the fatal seizures that year.
The jail subsequently tightened mail inspections. All packages and letters entering the facility are now tested for moisture. About one-fifth to one-quarter of the mail is found to contain abnormal moisture and is rejected. During cell searches, officers also focus on burn marks near books, letters and ventilation openings.
Illicit synthesis makes the supply chain harder to trace
In Chicago, a distributor working for a Mexican drug-trafficking group said supplies from Mexico continue despite the U.S. government's designation of some trafficking groups as terrorist organizations and its characterization of fentanyl as a weapon of mass destruction. He said shipments may be diverted underground or through other routes when they cannot cross the border, allowing the supply chain to adjust.
The distributor said the main change is the scale and variety of synthetic drugs. He acknowledged that the business has caused many deaths but continues to participate, arguing that the result justifies the means.
Dart, who has worked as sheriff for 20 years, said law enforcement once focused primarily on cross-border transport and traditional drug sources, including growing regions in Colombia, Mexico, China and Afghanistan. As synthetic drugs have spread, production can move into homes, basements and even bathrooms, making it impossible to cover every stage through supply-chain interdiction alone.
Dart said reducing demand also requires broader access to substance-use treatment and recovery programs. Cook County Jail operates several recovery initiatives, and he said addressing the long-term addiction problems faced by users is necessary to reduce repeated overdoses and deaths.
In a Chicago suburb, recovery worker Karen Bell helped a man with a severe wound on his leg. Bell previously used heroin and has not used hard drugs for 17 years. She said users can no longer be sure what is in a bag of drugs, while the wounds, withdrawal symptoms and other effects caused by the mixtures have become more complicated.
Recovery organizations are distributing test strips to detect fentanyl, medetomidine and xylazine. For emergency responders, recovery providers and users, uncertainty over a drug's contents remains the most immediate problem: naloxone can reverse an opioid overdose, but it cannot by itself address every effect caused by synthetic sedatives.