By Dr. Nicolette Natale

Last updated: 14 March 2024 & medically reviewed by Dr. David Miles

Xylazine, used initially as a non-opioid tranquilizer in veterinary medicine, has taken the American drug scene by storm. It proves to be both dangerous and sometimes deadly for its users. 

The combination of xylazine with other synthetic opioids like fentanyl, commonly referred to as "tranq dope" has caused a rise in overdose deaths in recent years due to the catastrophic physiological effects of combining these two highly sedative drugs. 

In this article, we will explore the pharmacological properties of xylazine, the emergence of "tranq dope" in the United States (U.S.), and its severe side effects. We will also dive into the potential for overdose, addiction, withdrawal, and available treatment options for those battling a xylazine addiction. 

Xylazine: Side Effects, Addiction, and Withdrawal

What is Xylazine?

Xylazine is a non-narcotic tranquilizer used in veterinary medicine for sedation, muscle relaxation, and pain relief. It is commonly referred to as a horse anesthetic.[1] 

Created in Germany in 1962 for use as an antihypertensive, the powerful central nervous system depressant led to profound sedation, drowsiness, amnesia, slowed breathing, heart rate, and dangerously low blood pressure levels, which led to approval being denied for use in humans.[1] 

Later, the Federal Drug Administration (FDA) approved it for use in veterinary medicine, in particular large animals like horses.[1]

 Xyalazine's mechanism of action

Xylazine is known as an alpha-2 adrenergic receptor agonist.[2] This means it works by binding and activating the alpha-2 adrenergic receptors of the cells in the brain and spinal cord.[2] This activation leads to the inhibition of the release of norepinephrine, an essential neurotransmitter in the nervous system.[1] The inhibition of norepinephrine release results in the inhibition of the sympathetic branch of the autonomic nervous system, which is responsible for our fight-or-flight response.[1] This response causes elevated blood pressure, increased heart rate, and constriction of blood vessels. A lack of norepinephrine activity leads to sedative and analgesic effects.

What is 'tranq dope'?

and other synthetic opioids, such as fentanyl and heroin. This deadly mixture has become increasingly prevalent in the illegal drug supply of the United States, often with opioid users being unaware that xylazine has been added to the mixture. 

The combination of these two potent sedatives may lead to the prolongation of the short high of these drugs, which also carries an increased risk of overdose and severe side effects such as skin ulceration and infections.[1] 

The stark rise in overdoses led to the FDA issuing a warning in November 2022 regarding the potential risks of xylazine exposure in humans after it was identified in the illicit drug supply in combination with drugs, such as heroin, fentanyl, cocaine, and even methamphetamine.[3] The FDA urges drug users to be on the lookout for drugs sold under the street name "tranq," "tranq dope," "sleep-cut," "Philly dope," and "zombie drug," which are known to contain xylazine and can cause toxicity resulting in decreased breathing, low blood pressure, low heart rate, and high blood glucose levels. These effects can be potentially fatal and do not respond to standard treatments for opioid overdose.[3]

The emergence of tranq dope in the U.S.

The use of xylazine as an additive in illicit drug mixtures has become a growing concern in the United States.[1][4][5] The White House has classified it as an emerging drug threat in the U.S. as overdoses and death tolls skyrocket. 

Xylazine was first found to be combined with heroin in Puerto Rico over twenty years ago. Since then, xylazine has increasingly spread throughout the United States, first making its mark as an additive in the street opioid supply in Philadelphia in the mid-2010s.[6] According to the most recent data, over 90% of Philadelphia's dope samples test positive for xylazine.[6] 

Since then, it has spread rapidly to other states in the United States, including Maryland, Connecticut, New York, and Rhode Island, and eventually making its way into Canada.[1][6] It has been detected in combination with other substances such as cocaine, benzodiazepines, and methamphetamine. A 2023 study detected xylazine in 413 out of 59,498 samples across 25 states, most frequently in combination with fentanyl.[1]

Unfortunately, the spread of xylazine doesn't come without consequences as overdose death tolls continue to rise. A Connecticut report implicated xylazine as the culprit in the rising overdose deaths from 2019-2020 in the state.[1] Additionally, a 2021 study evaluating data from 38 states and Washington D.C. found that xylazine was present in 1.8% of overdose-related deaths in 2019.[1] 

The presence of xylazine in drugs tested in labs increased in every region of the United States from 2020-2021, with the largest increase in the South.[4] A recent study from the Centers for Disease Control (CDC) found that the monthly percentage of deaths involving illegally made fentanyl with xylazine had risen from 3% in January 2019 to 11% in June 2022.[4] 

These alarming statistics have led to a National Response Plan issued by the White House to address the emerging threat of fentanyl combined with xylazine.[7] This plan outlines action steps and key responsibilities for departments and agencies across the federal government, including heightened awareness campaigns, intensified law enforcement actions targeting distribution networks, improved healthcare interventions, and legislative measures to reduce availability.[7] The goal of this National Response Plan is a 15% reduction of xylazine-related drug overdose deaths in at least three of four U.S. census regions by 2025.[7]

The FDA has also restricted imports of xylazine, to reduce easy access to the drug. The combination of these efforts hopefully will result in fewer xylazine-related deaths in the coming years. 

Side effects of xylazine

Xylazine's depressant effects on the central nervous system cause a slew of side effects, or what some users would describe as a "high" feeling.[1] 

The typical mild side effects of xylazine intoxication include [1]:

  • Sedation

  • Dry mouth

  • Hyporeflexia, or reduced reflexes

  • Pupil constriction

  • Disorientation

  • Dysarthria or difficulty speaking 

  • Lack of coordination of movement, or dysmetria

Moderate side effects of intoxication with tranq dope include [1]:

  • Low blood pressure

  • Low heart rate

  • Low body temperature

  • High blood glucose

As the dosage of tranq dope increases, side effects increase and can become lethal.

Severe side effects of tranq dope

Xylazine use, particularly in combination with other central nervous system depressants like fentanyl or heroin, can result in more severe side effects that can ultimately result in death. 

Severe side effects of tranq dope include [1]:

  • Reduced levels of alertness 

  • Coma

  • Severe muscle relaxation

  • Severely low or high blood pressure

  • Respiratory depression

  • Cardiac arrhythmias

  • Cardiac arrest 

The risk of severe side effects, overdose, or death is much greater when multiple substances, such as cocaine, heroin, benzodiazepines, and alcohol, are concurrently used.[1] 

Xylazine sores

Due to xylazine's strong vasoconstrictive properties, it reduces blood flow to certain areas of the body, such as the skin. Skin ulcers, sores, and abscesses similar to those found in methamphetamine addicts are common complications of chronic xylazine use.[1]

These skin ulcers, sores, or abscesses can be disfiguring if left untreated. They can also lead to severe complications, such as bacteremia, endocarditis, sepsis, limb amputation, and even death.[1]

Xylazine overdose

A xylazine overdose is a medical emergency that requires immediate medical attention. The symptoms of a xylazine overdose include [1]:

  • Heavy sedation 

  • Difficulty breathing

  • Extremely low blood pressure

  • Extremely low heart rate

  • Cardiac arrest

When used in combination with other opioids, the risk of overdose increases.[8] It is essential for users of opioids to be aware of the signs and symptoms of xylazine overdose and to seek immediate medical attention if they occur. 

Can naloxone help with xylazine overdose?

Naloxone, or Narcan, is a medication that can rapidly reverse the effects of commonly used opioids, such as fentanyl or heroin.[9] It is a life-saving medication for opioid overdoses with a rapid onset, resulting in the elimination of overdose symptoms.[9] 

Unfortunately, xylazine is not an opioid medication, so the use of naloxone will not reverse its effects. However, because xylazine is usually mixed with other substances, particularly opioids, naloxone is recommended in a suspected xylazine overdose.[1] Naloxone administration may reverse the effects of the opioid medication and provide life-saving improvements in blood pressure, heart rate, and respiratory rate.[9] 

Is xylazine addictive

On its own, xylazine is a highly addictive substance. It has been reported that xylazine addiction may be more robust than opioid addiction, including addiction to fentanyl.[1] It is presumed that the prolonged effects of xylazine can encourage addiction and dependency, which may complicate recovery.[1]

When used in combination with other opioids, the euphoric effects of opioids are enhanced, which may increase the risk of developing substance use disorder.[8] 

Xylazine withdrawal

Xylazine withdrawal can be a challenging process. Although withdrawal symptoms are not deadly, they can be extremely severe and include [1]: 

  • Anxiety

  • Restlessness

  • Insomnia

  • Muscle aches

  • Nausea and vomiting

These severe withdrawal symptoms are a part of what makes dependence on these substances so common. 

Treatment for xylazine withdrawal

Unlike the medication-assisted therapies for opioid withdrawal, there are currently no effective withdrawal treatments for xylazine, which may make abstinence from xylazine more difficult. 

However, with the rising number of xylazine-adulterated products, it has become increasingly important to identify effective treatments for these symptoms. 

Currently, there is limited literature on the management of withdrawal symptoms. One case report shows managing xylazine withdrawal using a combination of tizanidine, dexmedetomidine, and phenobarbital, followed by clonidine.[10] 

Similarly, the Philadelphia Department of Public Health released recommendations for managing withdrawal from xylazine by prescribing replacement therapy with alpha-2 adrenergic agonists, such as clonidine, tizanidine, dexmedetomidine, or guanfacine.[1] They also recommend pairing these agonists with pain management agents, such as short-acting opioids, gabapentin, ketamine, ketorolac, acetaminophen, or nonsteroidal anti-inflammatory drugs (NSAIDs).[1] 

They also recommend managing insomnia with trazodone, quetiapine, or mirtazapine, while anxiety-related symptoms should be treated with hydroxyzine or benzodiazepines.[1] 

The goal of xylazine withdrawal is to help reduce or eliminate the withdrawal symptoms to allow patients to come off of xylazine comfortably.

Xylazine resources

If you or someone you know are struggling with xylazine or tranq dope addiction and looking for more information, support, or treatment options, there are many resources available. 

The Substance Abuse and Mental Health Services Administration (SAMHSA) has a national helpline that is free, confidential, and open 24/7 to help individuals and families struggling with addiction.[11] They provide information on substance abuse treatment facilities, helplines, and support services.

Additionally, the CDC has a plethora of resources for the general public regarding xylazine use, including fact sheets, harm reduction strategies, test strips, overdose management, and wound care information.[12] 

If you need assistance or want to learn more, check out these resources to get the most up-to-date information on xylazine.