Illicit fentanyl is rarely sold in pure form. It is typically mixed with a combination of inert fillers to add bulk, active drugs that alter the high, and sometimes dangerous adulterants that the buyer has no way of detecting. The specific mix varies by region, supplier, and whether the fentanyl is sold as powder or pressed into counterfeit pills, but several categories of cutting agents show up consistently across the U.S. drug supply.
Inert Fillers That Add Bulk
The most common cutting agents are ordinary sugars and sugar alcohols: lactose, sucrose, dextrose, and mannitol. These are cheap, legally available, and look similar to powdered drugs. Their purpose is simple economics. Because fentanyl is active in microgram quantities, dealers need filler material to stretch a small amount of pure fentanyl into a sellable volume. A batch might be 95% or more filler by weight.
These inert fillers carry minimal health risks on their own, though they can cause nasal irritation when snorted. The real danger is inconsistent mixing. Because fentanyl is so potent, even slight clumping within a batch of filler means one portion could contain a harmless amount while the next contains a lethal dose. In counterfeit pills, the DEA estimated that by 2022, roughly six in ten seized counterfeit oxycodone pills contained 2 milligrams or more of fentanyl, considered a potentially lethal dose.
Xylazine: The Veterinary Tranquilizer
Xylazine is one of the most concerning adulterants in the current fentanyl supply. It is a sedative approved only for use in animals, and it has become widespread in street drugs. In 2024, 36 percent of fentanyl powder samples and nearly 6 percent of fentanyl pills tested positive for xylazine, with the highest concentrations in the Northeast, South, and Midwest.
Xylazine deepens and prolongs sedation beyond what fentanyl alone produces, which some users and dealers see as desirable. But it creates two serious problems. First, it causes severe skin wounds, even at injection sites and sometimes at distant locations on the body. These wounds range from surface irritation to deep tissue destruction that resembles a chemical burn, sometimes reaching bone. The tissue damage appears to result from xylazine’s direct toxicity to skin and blood vessels.
Second, xylazine does not respond to naloxone (Narcan). Naloxone reverses fentanyl’s effects on breathing, but because xylazine suppresses breathing through a completely different mechanism, a person who has taken both may continue to struggle to breathe even after naloxone is administered. First responders have noted that rescue breathing is especially important in these cases, and more than one dose of naloxone is often needed to counteract the fentanyl component alone.
Benzodiazepines and Designer Sedatives
Both prescription and illicit benzodiazepines frequently appear alongside fentanyl. These include standard pharmaceuticals like alprazolam as well as novel designer benzodiazepines not approved for medical use. Between 2019 and 2020, emergency department overdose visits involving both benzodiazepines and opioids jumped by 34.4 percent. During the first half of 2020, over 92 percent of fatal benzodiazepine overdoses also involved opioids.
Like xylazine, benzodiazepines slow breathing, and their effects stack on top of fentanyl’s respiratory depression. Naloxone will not reverse benzodiazepine sedation either, making these combinations particularly dangerous and harder for bystanders to manage during an overdose.
Nitazenes: Synthetics More Potent Than Fentanyl
A newer class of synthetic opioids called nitazenes has begun appearing in the drug supply, and some are dramatically more potent than fentanyl itself. Fentanyl is roughly 50 times stronger than heroin. Some nitazenes dwarf that figure: isotonitazene is an estimated 250 times stronger than heroin, and etonitazene reaches 500 times heroin’s potency. Even protonitazene, at 100 times heroin’s strength, is twice as potent as fentanyl.
Nitazenes have been detected in substances sold as other opioids, benzodiazepines, and even cannabis products. Their presence is especially dangerous because users have no way of knowing they’re consuming something far more potent than what they expected, and standard doses of naloxone may be insufficient to reverse an overdose.
Caffeine, Lidocaine, and Other Active Cuts
Several pharmacologically active substances are routinely used as cutting agents because they mimic certain properties of the drug being sold. Caffeine is commonly added because it vaporizes at a temperature that makes the product easier to smoke. Lidocaine and other local anesthetics are mixed in because they produce a numbing sensation that mimics the feel of cocaine or high-quality heroin when tested on the gums or tongue, giving buyers the false impression of purity.
These active cuts aren’t typically lethal on their own at the concentrations found in street drugs, but they add unpredictability to an already dangerous product. A user who relies on taste or sensation to judge potency is getting feedback from the cutting agent, not from the fentanyl content.
Fentanyl in Cocaine and Methamphetamine
Fentanyl doesn’t only appear in products sold as opioids. Community drug checking services have found fentanyl in roughly 12.5 percent of powder methamphetamine samples and 14.8 percent of powder cocaine samples. This cross-contamination is a major driver of overdose deaths among people who don’t use opioids intentionally.
The form of the drug matters. Crystal methamphetamine and crack cocaine are far less likely to contain fentanyl: less than 1 percent of crystal meth samples and zero percent of crack cocaine samples tested positive. Powder forms are more vulnerable to contamination, likely because they’re easier to mix or because they share equipment and packaging during distribution.
How Testing Strips Can Help
Fentanyl test strips and xylazine test strips are now widely available through harm reduction programs and some pharmacies. Fentanyl strips detect even trace amounts of fentanyl in a sample dissolved in water. Xylazine test strips have been validated with a sensitivity of about 97 percent and a specificity of 100 percent, reliably detecting xylazine at concentrations commonly found in street drugs.
These strips have real limitations, though. They tell you whether a substance is present, not how much. A positive fentanyl strip result from a cocaine sample tells you fentanyl is there but not whether the amount is a trace residue or a lethal dose. The strips also cannot detect nitazenes or novel synthetic opioids that are structurally different from fentanyl. A negative fentanyl test strip does not guarantee a sample is free of potent synthetic opioids.