Emerging National Security Threat: Xylazine Laced With Fentanyl Exacerbates Opioid Crisis

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In November 2022, the Food and Drug Administration (FDA) wrote a letter to stakeholders to describe a new drug that’s causing significant health risks in the U.S. The letter describes the drug xylazine, its origin, intended uses, illicit uses, and side effects. The letter warned treatment professionals, emergency room personnel, and the judicial and law enforcement community about the increasing presence of xylazine in the illicit drug supply, and what to watch for in people experiencing substance- or mental health-related emergencies.

Here’s an overview of the information provided by the FDA in that letter.

What is Xylazine?

Xylazine is a non-opioid agent that FDA originally approved in 1972 as a sedative and analgesic for use in veterinary medicine. There are no approved uses of xylazine for humans.

Xylazine and Illicit Drugs

Law enforcement has identified the presence of xylazine in:

  • Opioids:
  • Stimulants:
  • Opioids and Stimulants, e.g. speedball
    • When users combine opioids and stimulants, it’s called a speedball
    • Reports indicate users add xylazine to this combination to “offset the effects of the individual components” of the combined drugs

Street/slang names for xylazine include:

  • Tranq
  • Tranq dope
  • Sleep-cut
  • Philly dope
  • Zombie drug

Negative Health Consequences of Xylazine

The FDA indicates that xylazine toxicity may include:

  • CNS depression
  • Respiratory depression
  • Hypotension
  • Bradycardia
  • Hypothermia
  • Miosis, or high blood glucose levels

Chronic, repeated exposure to xylazine may include:

  • Dependence
  • Withdrawal symptoms, including:
    • Agitation
    • Severe anxiety
  • Intravenous use of xylazine is associated with severe, necrotic skin ulcerations

In addition, the FDA warned that although the effects of xylazine may mimic those of opioids, xylazine is not an opioid. This causes three additional problems:

  1. Naloxone – a.k.a. Narcan – cannot reverse a xylazine overdose.
  2. Standard toxicity screens – i.e. drug tests – cannot detect the presence of xylazine
  3. Medications for opioid use disorder (MOUD) typically used in medication-assisted treatment (MAT) for opioid use disorder (OUD), such as methadone, buprenorphine, and naltrexone, do not successfully manage xylazine withdrawal symptoms of reduce cravings

There are currently no FDA-approved medications to manage xylazine withdrawal, which makes xylazine a challenge for everyone involved. Its presence in the illicit supply of opioids increases the harm associated with the opioid epidemic, which has claimed over a million lives since 1999, and caused over one hundred thousand overdose fatalities in 2021.

The Drug Enforcement Agency and White House Weigh In

The FDA wrote that letter in November 2022 based on an unclassified report circulated to relevant government agencies the month before by the Drug Enforcement Agency (DEA), called “The Growing Threat of Xylazine and its Mixture with Illicit Drugs.” The FDA letter summarizes the contents of the DEA report, but also provides additional information that helps clarify the overall situation with regards to xylazine.

Here’s what they report:

  • Xylazine is easy to purchase online through pharmaceutical distributors that work with veterinarians
  • Xylazine is inexpensive
  • The psychoactive effects of xylazine allow drug traffickers to reduce the amount of opioids in illicit substances, which increase their profit
  • Since xylazine can extend the euphoric experience associated with opioid misuse, some users intentionally seek fentanyl or heroin with xylazine
  • Others have no idea what xylazine is or that it may be in the drug they ingest, leading to complications in an overdose situation: if the individual doesn’t know they ingested xylazine, medical personnel will not know to alter their emergency support appropriately

The DEA also includes the following statistics on xylazine-associated overdose fatalities.

Xylazine-Positive Overdose Deaths by Region (DEA Report)


  • 2020: 631
  • 2021: 1,281


  • 2020: 116
  • 2021: 1,423


  • 2020: 57
  • 2021: 351


  • 2020: 4
  • 2021: 34

From 2020 to 2021, those figures show a 103 percent increase in the Northeast, a 1,127 percent increase in the South, a 516 percent increase in the Midwest, and a 750 percent increase in the West. The DEA explains the regional variations in xylazine presence mimic the path fentanyl took in the mid-2010s. It began in the white powder heroin distribution centers in the Northeast, spread to the South, and later appeared in illicit drug supplies in the Midwest and Western U.S.

Those escalating numbers cause the FDA to write their general warning letter last November, and for the White House to identify xylazine as an emerging threat in an announcement on April 12th, 2023. We’ll discuss that announcement now.

Xylazine Warning from the White House

The announcement was – as many things over the past several years in the U.S. have been – unprecedented. The authority of an administration to designate an illicit drug as an emerging threat to our national security is new, bestowed by Congress in 2018.

In the past, emerging threats involved:

  • Military capabilities of international adversaries
  • Foreign espionage operations
  • Economic espionage/technology and intellectual property theft
  • Developing technologies and weaponry

Those threats are ongoing. This threat – in the form of a medication now used in the illicit drug supply – is new. That means it requires new strategies and new approaches to protect our citizens from its potential dangers.

According to the new guidelines created by the Office of National Drug Control Policy (ONDCP), a drug must meet the following five criteria to be designated as an emerging threat.

ONDCP: When Does a Drug Become an Emerging Threat?

A drug becomes an emerging threat to the national security of the United States when evidence shows it causes:

  1. An increase in morbidity or mortality due to drug overdose. Increases must occur in at least three census regions among the general population.
  2. An increase in polysubstance use and substance use disorders involving multiple substances. Increases must occur in at least three census regions among the general population.
  3. An increase in individuals or groups diagnosed with substance use disorder, or an increase in drug-related overdose rates. Increases must occur in a specific group in at least three census regions.
  4. An increase in emergency department visits, hospitalizations, or treatment related to the use of a new drug, class of drugs, or other substance. Increases must occur in at least three census regions.
  5. Increased reporting by health care providers or laboratories of new or novel clinical illnesses by patients with suspected or known exposure to a drug, class of drugs, or other substance. Increases must occur in at least three census regions.

When we read the report published by the DEA and the letter circulated by the FDA, we can see clearly that xylazine meets all these criteria. Here’s how the White House describes the threat in the press release entitled “Biden-⁠Harris Administration Designates Fentanyl Combined with Xylazine as an Emerging Threat to the United States.”:

“Levels of geographic distribution and rapid increase in negative health outcomes meet the Emerging Threats Criteria used by ONDCP to judge when the novel use of a substance should be considered as an emerging threat to the nation. While national overdose death numbers have flattened or decreased for seven straight months, xylazine is complicating efforts to reverse opioid overdoses with Naloxone and threatens progress being made to save lives and address the opioid crisis.

Now let’s take a look at the steps the White House plans to take to meet this emerging threat.

Action Steps: Countering the Impact of Xylazine

After the announcement we quote above, Dr. Raul Gupta, Director of the ONDCP, outlined the overall National Drug Control Policy, which we’ll discuss in another article. The announcement itself included their strategy for addressing the xylazine threat.

The xylazine strategy includes:

  • Developing new and more efficient protocols for testing for xylazine
  • Developing evidence-based treatment and supportive care of people with xylazine-related substance use disorder
  • Creating comprehensive data systems to track the source and supply of xylazine
  • Increased law enforcement focus on disrupting and preventing the illicit supply of xylazine
  • Rapid research efforts on the interactions between xylazine, fentanyl, and other opioids and substances of misuse

These steps align with the strategy to prevent the supply of illicit fentanyl in the U.S. Since xylazine and fentanyl are now two aspects of the same problem, the law enforcement actions to mitigate the harm caused by fentanyl now apply to xylazine.

These steps include, but are not limited to:

  • Coordinating a global law enforcement effort with international partners to disrupt the illicit synthetic drug trade
  • Promoting and strengthening information sharing among U.S. law enforcement and intelligence agencies
  • Partnering with private business to prevent them from being used/manipulated by drug traffickers to conduct business and expand distribution
  • Expanding efforts to identify and prevent drug traffickers from manipulating the U.S. financial system to hide, access, and launder drug profits

These efforts are important, because the initiatives in place at the local, state, and federal level have resulted in a levelling off of overdose deaths in the U.S. between 2021 and 2022. Preliminary data shows that our prevention, treatment, and harm reduction efforts are working. To protect this progress, it’s essential to address the harm caused by xylazine. We’ll close with the words of Dr. Gupta, from the emerging threat announcement in April 2023:

Fentanyl was dangerous before and it is even more dangerous now due to its combination with xylazine. Addressing the fentanyl crisis also requires addressing the drugs—in particular xylazine—with which fentanyl is being combined.
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