Illicit fentanyl is rarely pure. It typically contains a mix of inactive bulking agents, pharmacologically active adulterants, and, increasingly, other potent drugs that make overdoses harder to reverse. What’s in any given batch varies by region, form, and supplier, but several categories of additives show up consistently across drug seizures and testing programs nationwide.
Inactive Fillers and Bulking Agents
The simplest additives are cheap, white powders used to stretch the supply. Sugars, starches, lactose, and mannitol are common choices because they’re easy to buy, pharmacologically inactive, and look similar to fentanyl powder. These fillers carry minimal health risk on their own beyond minor nasal irritation, but they serve an important economic purpose: a small amount of fentanyl can be diluted into a much larger quantity of sellable product. The problem is that mixing is almost never precise, so one portion of a batch may contain far more fentanyl than another.
Active Adulterants That Mimic or Enhance Effects
Beyond simple fillers, illicit fentanyl frequently contains chemicals that are pharmacologically active. These are added to produce synergistic effects, enhance absorption, or simulate the feel of other drugs.
Caffeine is one of the more common stimulant adulterants. Combining a stimulant with an opioid can produce a longer-lasting euphoric effect while offsetting some of the sedation that opioids cause on their own.
Lidocaine, a local anesthetic, shows up regularly in seized samples. It creates a numbing sensation that can mimic the feel of cocaine, suggesting it may carry over from cocaine production rather than being intentionally added to fentanyl. It’s one of the most commonly encountered white powder additives alongside sugars and starches.
Diphenhydramine, the active ingredient in many over-the-counter sleep aids, is a sedative that can intensify fentanyl’s drowsy, euphoric effects. However, combining sedatives with opioids also increases the risk of dangerously slowed breathing, which is the mechanism behind fatal overdoses.
Xylazine: The “Tranq” Problem
Xylazine is a veterinary sedative designed for large animals like horses and cattle. It has become one of the most concerning adulterants in the fentanyl supply. DEA lab data from 2022 found that roughly 23% of seized fentanyl powder and 7% of seized fentanyl pills contained xylazine. In some regions the numbers are far higher: testing from eight syringe services programs in Maryland between 2021 and 2022 found xylazine in almost 80% of drug samples that also contained opioids.
Xylazine creates two specific dangers. First, it causes severe skin wounds, including ulcers, abscesses, and tissue death (necrosis) that can appear far from the injection site. Left untreated, these wounds can lead to amputation or become life-threatening. Second, naloxone (Narcan) has no effect on xylazine. Because xylazine suppresses breathing independently of opioid receptors, a person experiencing an overdose involving both fentanyl and xylazine may continue to have dangerously slow breathing even after naloxone is administered. Naloxone should still be given because it reverses the fentanyl component, but rescue breathing is especially important when xylazine is involved.
The geographic spread has been rapid. In Pennsylvania, the percentage of drug overdose deaths involving xylazine jumped from 2% in 2015 to 26% in 2020. Nationally, among deaths involving illicitly made fentanyl, xylazine detection rose from 3% in January 2019 to 11% by mid-2022. Standard fentanyl test strips cannot detect xylazine, so people have no way to screen for it with common tools.
Benzodiazepines and “Benzo Dope”
Benzodiazepines, the class of drugs that includes Xanax and Valium, are increasingly showing up in the illicit opioid supply. Street terms like “benzo dope” describe fentanyl that has been cut with these sedatives. People may be taking benzodiazepines alongside fentanyl knowingly or without realizing it.
This combination is particularly dangerous because both drug classes suppress breathing. When taken together, the risk of fatal respiratory depression is significantly higher than with either drug alone. Like xylazine, the benzodiazepine component of an overdose will not respond to naloxone, since naloxone only reverses opioid effects.
Fentanyl Showing Up in Stimulants
Fentanyl contamination isn’t limited to the opioid supply. A study analyzing 718 confirmed samples of methamphetamine and cocaine from community drug-checking services found fentanyl in about 12.5% of powder methamphetamine and 14.8% of powder cocaine samples. The rates varied significantly by location.
Crystalline forms carried far less risk: fewer than 1% of crystal methamphetamine samples and zero crack cocaine samples contained fentanyl. This suggests that powder drugs, which are easier to mix and cross-contaminate during handling or packaging, pose the greater risk of inadvertent fentanyl exposure. For someone who uses stimulants and has no opioid tolerance, even a trace amount of fentanyl can be lethal.
Nitazenes: A Newer Threat
Nitazenes are a class of synthetic opioids that are increasingly being detected in the U.S. and European drug supplies. They have been found mixed into heroin, fentanyl, and even counterfeit versions of prescription drugs like oxycodone and alprazolam. Some nitazene compounds are significantly more potent than fentanyl, which raises the overdose risk even further. Their presence in the supply is still relatively new, but detection rates are climbing.
Why Testing Strips Have Limits
Fentanyl test strips are a widely recommended harm reduction tool, but they have notable blind spots. Lab testing has found that several common adulterants cause false positives, including diphenhydramine, lidocaine, MDMA, and methamphetamine. This means a positive result on a test strip doesn’t always confirm fentanyl is present, and substances like xylazine and nitazenes won’t trigger a positive result at all because the strips aren’t designed to detect them.
The practical takeaway is that test strips are useful but imperfect. A negative result reduces the likelihood of fentanyl contamination, but no strip can provide a complete picture of everything in a sample. More advanced drug-checking services, where available, use lab equipment that can identify a broader range of substances.