Illicit Opioid Drugs Are Rarely What They Seem
From quinine, fentanyl, xylazine to lidocaine today and nitrazenes tomorrow.
Updated August 19, 2025 | Reviewed by Monica Vilhauer Ph.D.
Illicit drugs aren’t tested by the FDA or pure, nor as advertised by drug dealers. Illegal drugs are cartel-driven around profit maximization, cash-only trading, and a form of entrepreneurship. Dealers cut drugs to increase bulk and maximize sales. They also adulterate drugs to boost subjective potency. In addition, dealers use other drugs to mask poor quality or maintain a texture/color.
When Herb Kleber and I worked at Yale’s School of Medicine addiction evaluation and treatment programs, we observed street heroin was rarely pure. Starches, sugars, talc, or powdered milk were added to street supplies to increase volume. In 1975, quinine was so common an adulterant, we often identified heroin users by finding quinine in their urine.
By the 1990s–2000s, adulterants included toxic agents like levamisole, (an animal anti-parasitic). The analgesic acetaminophen was often added, as was dextromethorphan, an over‑the‑counter cough suppressant.
Cocaine has been one of the most adulterated street drugs since the 1980s. In some cities, over 70% of street cocaine contains levamisole. Lidocaine and benzocaine were/are used to mimic the numbing effects of pure cocaine. I remember a celebrity drug bust for cocaine, which turned out to be Sudafed (an old cold medicine) and lidocaine with phenacetin, a banned analgesic, added for its white color. Often, methamphetamine is cut with caffeine, ephedrine, or dimethylsulfone (“MSM”) to increase bulk or simulate cocaine’s appearance.
What Makes Today’s Fentanyl Supply Different?
What sets illegally manufactured fentanyl (IMF) apart today isn't adulteration but the scale, potency, unpredictability, and number of Americans at risk from the adulteration. In a national survey of 1,515 adults conducted in June 2024, 166 respondents (11.0%) reported illicit opioid use and 114 (7.5%) reported illicitly manufactured fentanyl (IMF) use within the past 12 months. These rates are much higher than previously reported estimates.
Fentanyl is 50–100x more potent than morphine, thus even minute changes can be lethal. Many adulterants (xylazine, local anesthetics) aren’t responsive to naloxone (Narcan) or routine overdose management . The speed with which new agents enter the illicit drug supply is faster than ever before. This makes harm reduction often feel like a horrible game of "Whack-a-Mole."
David M. Martin, PhD, Science Team Director of the Global Toxic Adulterant Project of the U.S. State Department and the Colombo Plan, helped redefine the opioid and stimulant supply chain from source countries by testing illicit drug formulations from source to streets. Dr Martin told me, “There are profound changes in street drugs that jeopardize the health of substance users worldwide with multiple pharmaceuticals, toxic adulterants, veterinary medications, and novel psychoactive substances (NPS) not seen in the last 50 years of research in this area.” Dr. Martin said many users ingest 3–5 pharmacologically active agents in one dose, often unknowingly. With drugs that are powders and pressed pills, it’s hard/impossible to tell what’s inside these drugs. Harm reduction advocates have tried to develop methods to test drugs, but often such testing occurs after a catastrophe, spurring new additives and changes that go undetected.
A few years ago, veterinary tranquilizers, anesthetics, and α2-agonists like xylazine and medetomidine were introduced as Tranq Dope. I reviewed these previously .
The rise of these compounds signaled an intent shift—adulterants were no longer added solely for profit or potency, but also for user-perceived subjective effects like more prolonged sedation or smoother intoxication. This made adulteration harder to predict and more challenging to mitigate in clinical practice. These agents also made overdose reversal increasingly difficult, as they required prolonged resuscitation efforts and aggressive supportive care, often without a specific antidote.
Surge in Lidocaine, Procaine, and Other Local Anesthetic Adulteration
According to the recent article by NYU’s Joseph Palamar et al., adulteration of fentanyl with local anesthetics has surged dramatically. Most recently, illegally manufactured and street-sold fentanyl contains local anesthetics like lidocaine, procaine, tetracaine, benzocaine, and bupivacaine, added to fentanyl to mimic a speedball. (A speedball is a drug combination of a depressant and a stimulant.)
Based on data from the National Drug Early Warning System (NDEWS) and the CFSRE’s NPS Discovery program (an open-access drug early warning system), there was a 705% increase in IMF–lidocaine codetections from 2022 to 2024. By December 2024, nearly 30% of IMF samples contained multiple anesthetic agents. Yet traditional fentanyl test strips do not detect these adulterants, giving users a false sense of security.
The Nitazenes Opioids
Nitazenes (e.g., isotonitazene ; protonitazene) are a class of opioids synthesized in the 1950s for pain relief but abandoned due to overdose risks. Potency varies widely. The most potent forms can be 43× more powerful than fentanyl. Some analogs reach potency levels of roughly 1000× morphine.
I asked U.F. Dean Dr. Linda Cottler about National Drug Early Warning System (NDEWS) insights on nitazenes. She pointed me to a report covering January 2023 to April 2025 showing that most nitrazene overdoses occurred in the southeastern region of the United States. Dr Cottler said the University of North Carolina at Chapel Hill's (UNC) Street Drug Analysis Lab detected nitazenes in 135 samples from 14 states as of the end of April 2025. Yet labs often miss these drugs because they are either not tested for or are present in tiny amounts. When detected, they have frequently been found with fentanyl or benzos. The UNC report can be found here .
Although naloxone can reverse nitazene overdoses, even tiny amounts can be lethal, and high or repeated doses of naloxone may be required. Nitazenes may be trending downwards, as in June 2025, China's Ministry of Public Security announced placing nitrazene analogues under national control. But it is unclear what, if any, impact this announcement will have on Nitazenes .
The most recent adulteration development in 2025 was the detection of BTMPS, an obscure industrial chemical often used in plastic and polymer production, and also used as a fentanyl adulterant.
BTMPS is among the top 10 compounds detected in January 2025 IMF samples. While the intent of including BTMPS is unclear—perhaps as a bulking agent or cutting substance—its presence has alarmed public health and forensic experts due to its unknown toxicity.
Overdoses should be managed as usual (airway, ventilation, repeat naloxone as indicated), recognizing BTMPS does not change naloxone’s responsiveness to fentanyl.
The adulteration of illicit drugs has been a recurring feature of unregulated drug markets for decades. What we’re seeing now is an extreme escalation in a long-standing trend, marked by higher potency, greater adulterant diversity, fentanyl toxicity, and more lethal consequences. As a result, the current IMF environment is significantly more dangerous and less predictable going forward than in previous drug eras.
Palamar JJ, DeBord JS, Krotulski AJ, Goldberger BA. Local Anesthetics Adulterating the Illicit Fentanyl Supply. JAMA Psychiatry. 2025;82(8):755–756. doi:10.1001/jamapsychiatry.2025.0952)
Powell D, Jacobson M. Estimates of Illicit Opioid Use in the US. JAMA Health Forum. 2025 May 2;6(5):e250809. doi: 10.1001/jamahealthforum.2025.0809. Erratum in: JAMA Health Forum. 2025 Jun 7;6(6):e252563. doi: 10.1001/jamahealthforum.2025.2563. PMID: 40343715; PMCID: PMC12065033.
Shover CL, Godvin ME, Appley M, et al. UV Stabilizer BTMPS in the Illicit Fentanyl Supply in 9 US Locations. JAMA. 2025;333(11):1000–1003. doi:10.1001/jama.2024.27550
Martin, David M. Jones, Joseph Costantino, Anthony et al. Characteristics and Laboratory Testing Standards for Drugs of Abuse, Editor(s): John D. England, Encyclopedia of the Neurological Sciences (Third Edition), Academic Press, 2025, Pages 277-302, ISBN 9780323957052, https://doi.org/10.1016/B978-0-323-95702-1.00010-5 .
Murphy L, Krotulski A, Hart B, Wong M, Overton R, McKeever R. Clinical characteristics of patients exposed to medetomidine in the illicit opioid drug supply in Philadelphia - a case series. Clin Toxicol (Phila). 2025 Jun;63(6):438-441. doi: 10.1080/15563650.2025.2500601. Epub 2025 May 21. PMID: 40396666. Abstract
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Mark S. Gold, M.D., is a pioneering researcher, professor, and chairman of psychiatry at Yale, the University of Florida, and Washington University in St Louis.
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