United States Drug Enforcement Administration

The United States continues to face an unprecedented and evolving drug threat driven by illicit fentanyl, which is increasingly mixed with a dangerous array of synthetic substances emerging in the illicit market. These combinations are making an already deadly drug supply even more unpredictable and lethal.

Law enforcement and public health officials are seeing fentanyl combined with highly potent substances such as xylazine, nitazenes, cychlorphine, and medetomidine. Many of these substances are not approved for human use and are often undetectable to the user.

Xylazine and medetomidine are used by veterinarians to sedate animals. Nitazenes and cychlorphine are potent, unregulated, synthetic opioids. New nitazenes tend to be introduced when regulatory actions, enforcement, and drug scheduling put pressure on existing analogues. DEA has reported 22 unique nitazenes compounds since 2020, 21 of which are listed as Schedule I controlled substances. 

Why This Matters:

• Extreme Potency: These emerging synthetic drugs can be significantly more powerful than fentanyl and greatly increase the risk of suffering a fatal overdose.
• Hidden Mixtures: These substances are frequently mixed into counterfeit pills or fentanyl powder without the user’s knowledge.
• Reduced Reversal Effectiveness: Drugs like xylazine and medetomidine are not opioids, meaning naloxone may not fully reverse their effects, complicating overdose response. Other synthetics, such as nitazenes and cychlorphine, might require several doses of naloxone to be effective. 
• Severe Health Impacts: Xylazine has been linked to devastating soft tissue damage, infections, and prolonged sedation, while other synthetics can cause rapid respiratory depression and death.

Public Safety Guidance:

• Never take a pill that wasn’t prescribed to you and dispensed by a licensed pharmacy.
• Assume all illicit drugs may contain fentanyl or other deadly additives.
• Carry naloxone and be trained in how to use it but understand it may not fully reverse all substances present.
• Call 911 immediately in any suspected drug poisoning or overdose. Time is critical.
• Stay informed and spread awareness. This threat is evolving rapidly.

Today’s illicit drug supply is more dangerous, more deceptive, and more deadly than ever before. One pill, one try can kill.

Public awareness and prevention are critical. For more information, visit DEA.gov/fentanyl free and DEA.gov/onepill. 

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