There is a paradox in the current drug overdose crisis. For the first time in years, opioid overdose deaths are significantly declining—by over a third in some measures. However, the illicit drug supply is not disappearing; it is transforming.
Fentanyl has been the dominant, potent base of the illicit opioid market for the last decade. However, one study showed that after a 25-fold increase in 15 years, fentanyl deaths peaked with some 73,000 fatalities in 2023 but turned suddenly downward at midyear [1].
In this article, I look at changes in the fentanyl market, supply, and use; why fentanyl is in non-opioid drugs; powerful new adulterants; the lethal consequences; and the clinical implications and harm reduction initiatives.
Economic and Supply-side Reasons
When OxyContin was reformulated in 2010 to be abuse-deterrent, it didn’t eliminate demand; it pushed users toward heroin, igniting the next wave of the epidemic.
Fentanyl is 50–100 times more potent than morphine and far stronger than heroin, so a tiny amount can replace a much larger quantity of other opioids while producing a similar high.
It is relatively inexpensive to synthesize, easy to press into counterfeit pills or mix into powders, and far cheaper per “dose” than heroin or diverted oxycodone.
Producers and dealers can “stretch” more expensive drugs (e.g., heroin, oxycodone) by cutting them heavily with fillers and then adding a small amount of fentanyl to restore perceived strength, increasing profit margins.
Because it’s compact and potent, it is easier and more profitable to traffic than bulkier plant-based opioids like heroin, contributing to a shift from heroin to illicitly manufactured fentanyl in the street supply since around 2015–2016.
A Global Fentanyl Market in Transition: It’s Whack-a-Mole
By the end of 2024, the annual rate of fatal fentanyl overdoses had fallen by over a third, according to statistics from the Centers for Disease Control and Prevention [1].
The previously mentioned study reported that this reversal was likely driven not by changes in domestic treatment or prevention efforts, but by a disruption in the global supply of illicit fentanyl. This was most likely due to restrictions on precursor chemicals used in its production in China. How long this scenario will last is unknown and difficult to predict.
However, the agility of illicit drug manufacturers knows no bounds. Now fentanyl is increasingly showing up mixed with other drugs—particularly veterinary tranquilizers like medetomidine and xylazine—not by accident, but as a direct result of market forces.
Crackdowns on one substance simply cause traffickers to innovate and substitute with new, often more dangerous compounds in a continuous “whack-a-mole” cycle.
Traffickers, needing to maintain profit margins and product volume, began seeking new, legal, or less-regulated chemicals to cut with or replace scarce fentanyl. This led to the rise of veterinary sedatives.
Why Fentanyl Is In Non-opioid Drugs
Fentanyl is sometimes intentionally added to stimulants like cocaine or methamphetamine and to MDMA to intensify or modify the high, increase “addictiveness,” and encourage repeat business from customers who perceive the product as unusually strong [2].
In other cases, non-opioid drugs become contaminated because the same surfaces, tools, and scales are used to cut and package multiple substances; with fentanyl’s potency, even trace residue can produce clinically significant contamination.
Counterfeit prescription pills (sold as “Oxycodone,” “Percocet,” “Xanax,” “Adderall,” etc.) are often actually pressed with fentanyl or methamphetamine instead of the advertised medication, so people think they are taking a known dose of a legit pill but are actually consuming fentanyl [3] [4].
The crackdown on prescription opioid diversion and some heroin supply routes created an opportunity for illicitly manufactured fentanyl to fill demand because it does not depend on poppy cultivation and can be mass-produced in clandestine labs.
As fentanyl became the main opioid in the market, it started to “bleed” into many street drug categories simply because the same networks and spaces handle multiple substances, and there is no quality control.
The result is that people who do not identify as “opioid users” (e.g., those using only cocaine or party drugs) are now at risk of opioid overdose because of hidden fentanyl in their supply.
The New Adulterants: From Xylazine to Medetomidine
Xylazine (“Tranq”) was the first major adulterant. It extended the short high of fentanyl but caused severe side effects like sedation and horrific flesh wounds.
As states like Pennsylvania began scheduling xylazine, its presence dropped. It was almost immediately replaced by medetomidine (“Rhino Tranq”), an even more potent animal tranquilizer (100-200x stronger than xylazine) [5].
In Toronto, Canada, for example, medetomidine is now found in up to 80% of fentanyl samples, up from just 25% in early 2025 [6]. And reports out of the U.S., particularly in Philadelphia, show the drug has increased hospitalizations, including stays in intensive care units.
Why Are These Substances Being Mixed?
There are several reasons [1]:
- Economic Motivation (The “Profit Motive”): These adulterants are cheap and potent. A small amount can “stretch” a supply of fentanyl, maximizing profits for traffickers.
- Extending the High: Fentanyl’s euphoric effects are intense but very short. Mixing it with long-acting sedatives like medetomidine creates a more sustained, sedated state that users may inadvertently seek, even though it drastically increases health risks.
- Bypassing Detection: Using novel, unscheduled chemicals helps producers evade law enforcement and customs controls that target known fentanyl precursors
The Lethal Consequences for the User
There are numerous very serious consequences for users [5] [7].
- The “Unpredictable Cocktail”: People who buy what they think is fentanyl, or even cocaine or counterfeit pills, are often consuming a mystery mix of potent opioids and veterinary sedatives without their knowledge.
- Naloxone is No Longer Enough: This is a critical point. Naloxone (Narcan) reverses opioid overdoses but does nothing for xylazine or medetomidine. First responders are now dealing with patients suffering from profound sedation, low blood pressure, and cardiac issues that standard antidotes can’t fix.
- New Health Crises: These mixes are causing a surge in ICU admissions for severe withdrawal, limb amputations from tissue necrosis, and organ damage from prolonged suppressed breathing.
Clinical and Harm Reduction Implications
The very features that make fentanyl attractive to illicit markets—high potency, low cost, easy mixing—also dramatically raise overdose risk, because minute dosing errors can turn a “normal” batch into a lethal one [7].
Core harm reduction responses to this new supply reality include:
- Drug checking (e.g., fentanyl test strips, spectroscopy services)
- Expanded naloxone distribution
- Messaging that “any pill or powder not from a pharmacy may contain fentanyl.”
Key Takeaways
- The contamination of fentanyl is a direct consequence of supply-side enforcement in a persistent market. As long as demand exists, the market will innovate to meet it.
- This volatility makes the current crisis fundamentally different from the past. Treatment and emergency response must evolve just as quickly as the drug supply.
- The decline in overdose deaths is fragile and welcome. However, the rise of these complex poly-drug cocktails presents a new, more complicated challenge that requires a nimble, health-focused response rather than relying on enforcement alone.
Find Supportive Care at Red Rock Recovery
Substance use disorder, or addiction, can feel insurmountable, but Red Rock Recovery Center is here to help you begin your recovery journey today with our core values of Community, Connection, and Purpose and a trauma-informed approach.
Red Rock Recovery Center stands out from most drug and alcohol rehab centers in Colorado by offering a full continuum of care approach to substance use disorder (SUD) and addiction treatment.
Our Colorado rehab center is proud to offer an addiction treatment program that includes all necessary steps to healing, from medical detox to aftercare services. Located close to major cities such as Colorado Springs, we are uniquely equipped to help countless families find healing.
Sources
[1] Driscoll G 2026. Study: Global Fentanyl Supply Disruption Led to Drop in Opioid Overdose Deaths. Maryland Today.
[2] O’Donnell J, et al. Drug Overdose Deaths with Evidence of Counterfeit Pill Use — United States, July 2019–December 2021. MMWR Morb Mortal Wkly Rep 2023;72:949–956.
[3] Drug Enforcement Agency. nd. Counterfeit Pills.
[4] Friedman, J., et al. (2023). Fentanyl, Heroin, and Methamphetamine-Based Counterfeit Pills Sold at Tourist-Oriented Pharmacies in Mexico: An Ethnographic and Drug Checking Study. medRxiv : the preprint server for health sciences, 2023.01.27.23285123.
[5] Leggin J. 2025. The Illicit Opioid Market: Patterns and Implications. The Rothman Institute. Foundation for Opioid Research and Education.
[6] Draaisma M. 2026. Animal tranquilizer being mixed with fentanyl in Toronto’s illicit drug supply, experts warn. CBC News.
[7] Macmillan C. 2024. Why Is Fentanyl Driving Overdose Deaths? Yale Medicine