Xylazine Toxicity

What is Xylazine Toxicity?

Xylazine is a non-narcotic substance that’s often used in veterinary medicine to sedate animals, relieve their pain, and relax their muscles. It’s sometimes referred to as “anestesia de caballo” or “horse anesthetic.” This medication is a version of a drug called clonidine that was discovered by German Farbenfabriken Bayer in 1962. Initially, the idea was to use it to decrease high blood pressure in humans, but it was found to lower blood pressure severely and make people excessively sleepy.

Eventually, xylazine was introduced as a medication for animals, not humans, to make them feel sleepy, induce vomiting, relieve pain, and relax muscles. This use of the drug started in the late 1960s. Today, it’s a commonly used non-addictive tranquilizer in veterinary medicine. In research studies involving animals like dogs, cats, horses, rabbits, and rats, xylazine is often used alongside an anesthetic drug called ketamine.

However, xylazine has recently become a popular illegal drug among people who inject drugs. This started in Puerto Rico in the early 2000s. Data on the illegal use of xylazine, its prevalence in different parts of the world, and its immediate and long-term effects on humans is limited. The misuse of xylazine has recently increased in the northeastern US and is spreading across many states, as seen from the growing number of drug samples testing positive for it. In Philadelphia, xylazine is commonly known as “tranq”. When mixed with other widely used illegal drugs like heroin or fentanyl, the mixture is referred to as “tranq dope”.

It’s often combined with synthetic drugs like fentanyl in the unregulated market. It’s also been found with drugs like cocaine and methamphetamine, and more recently, it’s been mixed with oxycodone and alprazolam. It’s believed that the xylazine used for recreational purposes comes from the supply intended for animal use.

The rapid spread of xylazine is due to various factors such as cost-cutting, its addictive qualities, and its ability to extend the duration of the opioids it’s combined with. The use of xylazine is a problem for the US healthcare system since the drug can have serious consequences for people who knowingly or unknowingly use it. This is compounded by the lack of information about xylazine and the absence of an approved antidote for it.

What Causes Xylazine Toxicity?

For use in animals, xylazine comes in a liquid form that can be injected. It comes in different strengths: 20 mg/mL, 100 mg/mL, and 300 mg/mL. This liquid can be dried to make a powder or be mixed with salt. The powder can be white or brown.

Sometimes, xylazine is mixed with illegal drugs for various reasons.

The powder can be used to add volume to street drugs like heroin and fentanyl. Because it’s hard to tell xylazine apart from other powders, it can be mixed with them or crushed into tablets to make more of a drug. The fact that xylazine is easy to get, cheap, and can increase the effect of opioids makes it appealing for those selling drugs, as it allows them to use less heroin or fentanyl and make more money. However, most people actually don’t want xylazine mixed in with their opiates, according to a survey from a popular social media site, Reddit. When mixed with stimulants, xylazine can help to reduce unwanted side effects and withdrawal symptoms.

Taking too much of a drug mixed with xylazine can cause severe problems, like extreme tiredness, trouble breathing, slow heart rate, low blood pressure, and in very serious cases, the heart stopping completely. Long term use of these mixed substances can cause ongoing toxic effects, leading to things like chronic wounds and skin ulcers. Xylazine use in people is a complicated issue, and we need more research to understand why it’s being abused.

Risk Factors and Frequency for Xylazine Toxicity

Xylazine is a substance that has been increasingly found in illegal drugs, making an already serious opioid crisis even worse. The danger of xylazine wasn’t fully known before its use became widespread.

Before the year 2000, it was rare to hear about xylazine intoxication in people. It initially became a more common ingredient in Puerto Rico and then spread to Puerto Rican communities in the United States. Users of injectable drugs and health workers started to notice more xylazine in Philadelphia’s street opioids since the mid-2010s.

By 2014, xylazine was found in recreational drugs like heroin or mixed opioid-stimulants known as “speedballs.” Between 2015 and 2021, it was reported to be combined mostly with drugs like fentanyl, cocaine, benzodiazepines, methamphetamine, and heroin. In Canada, multiple other similar substances were also often found with xylazine. In the state of Rhode Island in the U.S., a 2022 study found that xylazine was increasingly mixed with popular drugs like Percocet (oxycodone and acetaminophen) and Xanax (alprazolam). These findings show xylazine is being combined with more and more substances.

• In Connecticut, recent records linked xylazine to an increasing number of overdose deaths in 2019 and 2020.
• A 2021 study of data from 38 states and Washington, D.C., showed that xylazine was found in 1.8% of overdose-related deaths in 2019.
• Another study found xylazine in 10 different areas across the U.S., with Philadelphia having the highest rate of xylazine-related deaths (25.8%), followed by Maryland (19.3%), and Connecticut (10.2%).
• In 2021, Philadelphia’s Department of Public Health found that 91% of supposed heroin or fentanyl samples from the area contained xylazine, making it the most common additive in the local drug supply.

A 2023 study analyzed almost 60,000 drug samples collected from people aged 20 to 73 across 25 states. These samples were taken when doctors ordered tests. The most common substances found were fentanyl, buprenorphine, nicotine, cocaine, naloxone, D-methamphetamine, and delta-9-tetrahydrocannabinol, with xylazine being quite common. Among a group of similar substances known as designer benzodiazepines, etizolam and clonazolam were the most commonly detected. Ethnographic evidence indicates that xylazine is extremely harmful to those who inject drugs. Numerous recent studies suggest a sharp increase in the percent of deaths linked to xylazine or other drugs when combined with it.

Signs and Symptoms of Xylazine Toxicity

Xylazine toxicity can be hard to identify because it is often mixed with other substances. Its symptoms can include feelings of euphoria, sedation, dry mouth, slurred speech, low reflexes, confusion, poor coordination, small pupils, low blood pressure, slow heartbeat, low body temperature, and high blood sugar. If it is combined with other substances that also depress the central nervous system, such as opioids, benzodiazepines, or alcohol, it can lead to severe central nervous system depression, with signs like unresponsiveness, coma, muscle relaxation, and sometimes abnormal blood pressure, slow or no reflexes, weakness or no breath at all, and heart irregularities or stoppage.

The pleasurable effects of xylazine can last up to 6 hours, which can make users seek out another dose while they are still high. This makes quitting the drug difficult. It becomes even more difficult because standard medications for opioid withdrawal don’t work for xylazine withdrawal. Frequent use of xylazine mixed with drugs like heroin and fentanyl can cause serious skin problems and infections. These can increase the risk of getting bloodstream infections, heart infection, full-body infection, limb removal, and even death. Any patient with a hard-to-heal ulcer, whether they inject the drug or not, should be checked for xylazine usage.

Xylazine is most often mixed with another drug called fentanyl. People under the influence of this combination will show signs of opioid poisoning, such as small pupils along with central nervous system and breathing depression. They might also display rapid, involuntary eye movements due to the xylazine. Fentanyl and xylazine both work together to depress the central nervous system and breathing, which could lead to full stoppage and death. If a person shows signs of fentanyl overdose but doesn’t improve much after being given naloxone (a medication that reverses opioid overdose), they might have overdosed on xylazine or another substance.

It is essential to educate people who use illicit substances on the signs, symptoms, and potential outcomes of overdosing on xylazine. They should also be taught the benefits of using naloxone in cases of opioid overdose, even if the opioids are mixed with xylazine. While naloxone doesn’t reverse the symptoms of xylazine use, reversing the symptoms of opioid use can reduce the overall risk of dying.

Testing for Xylazine Toxicity

If you are suspected of having overdosed on a drug called xylazine, your doctor will take similar steps as if you’d overdosed on any other substance. The first things they’ll look to secure is your ability to breathe and your overall blood flow. They’ll assess your mental state and try to get your full medical history if they can. They’ll also perform a physical examination, a test to measure your blood sugar levels, and, for women, a pregnancy test.

Unfortunately, typical drug screenings that are done on urine samples do not usually pick up xylazine. These drug screenings are focused on the five substances people most commonly abuse: opiates, cannabinoids (marijuana), amphetamines, cocaine, and phencyclidine (a hallucinogen also known as PCP). Patients on prescription pain medications are also tested for benzodiazepines, barbiturates, and methadone, using more specialized tests. In cases of drug overdose, these tests can also assess levels of other drugs like LSD, propoxyphene, buprenorphine, tramadol, fentanyl, and oxycodone.

To confirm that there is xylazine in a urine sample, more expensive and time-consuming testing procedures–like gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry–are needed. However, these tests don’t provide immediate results and can take up to a week. This makes them impractical for real-time treatment decisions.

There’s also the issue that xylazine passes through the body very quickly, which increases the likelihood of false-negative test results. More research will be needed to develop cost-effective tests that can detect xylazine more quickly and accurately.

In response to the growing problem of xylazine abuse, a more economical test has been developed that uses a method called lateral flow immunoassay to test for xylazine. This test has a detection sensitivity of up to 1000 ng/mL and can be used to test the substance itself. People suffering from substance abuse disorder have access to these test strips, which can be bought online or obtained through harm-reduction programs. Occasionally, but quite rarely, these strips are used in healthcare settings, although they have limited value in such settings. This is because patients who have just taken the drug usually don’t have it with them. However, as a tool for reducing harm, they can be very useful.

Treatment Options for Xylazine Toxicity

If someone is suspected of overdosing on xylazine, an emergency medication called naloxone should be given and the person should be placed in a specific position, known as the “recovery position”. This position helps to keep the person’s airway clear and prevents choking, especially if they are unconscious but still breathing on their own. Here’s how you do it:

* First, kneel next to the person.
* Stretch out the arm that’s closest to you above their head.
* The other arm should cross their body, with their hand on their cheek that’s closest to you.
* Bend the knee that is furthest from you and place it flat on the ground.
* Then, gently roll the person onto their side facing you.
* Tilt their head back to open their airway and remove any obstruction if you can.
* Adjust their upper leg so the hip and knee form two right angles.
* Stay with the person and keep checking their breathing.
* If necessary, you may need to give them rescue breaths or start chest compressions.

As of 2023, there is no drug approved by the FDA (the main U.S. health regulator) that can specifically counter the effects of xylazine. Instead, doctors treat the symptoms which can include giving oxygen, managing breathing, giving intravenous fluids, replenishing electrolytes, and treating high blood sugar. Medicines that can depress the central nervous system should be avoided. If opioids, a type of pain medication, have also been taken, naloxone should also be provided. Long periods of sedation can increase the risk of a blood clot, so this needs to be watched for.

If the drug has caused skin ulcers, there’s a specific procedure for care:

* First, the wound is cleaned.
* Then, doctors will check if secondary infection occurred.
* A special gauze and topical ointment are applied.
* The dressing is changed daily.
* Any dead tissue is removed from the ulcer
* In serious cases, some patients might need skin grafts or, at worst, amputation.
* Antibiotics may also be required to prevent any additional infection.

With regular use of xylazine, withdrawal symptoms can appear. However, there’s limited information on how to treat these symptoms. One report noted the use of multiple drugs used in combination to manage withdrawal; the drugs included tizanidine, phenobarbital, and dexmedetomidine followed by an ongoing course of clonidine, buprenorphine, and gabapentin.

The public health officials in Philadelphia have offered their own advice on managing withdrawal symptoms. They recommended using one of several known drugs for withdrawal symptoms along with short-term opioids, pain relievers, and anti-inflammatory drugs. They also recommended medications for sleep, if needed, and treating any anxiety or restlessness. Any withdrawal symptoms due to opioids should be treated immediately. Unfortunately, traditional therapies designed to help with opioid withdrawal might not work with xylazine as it is not an opioid.

What else can Xylazine Toxicity be?

If someone overdoses on xylazine, their symptoms might appear similar to those of the following medical emergencies:

• Fainting (syncope)
• Low blood sugar (hypoglycemia)
• Low body temperature (hypothermia)
• Seizure disorders
• Stroke (cerebrovascular accidents)

There are also other types of drug overdoses that share symptoms with xylazine overdose. For example:

• Opioid overdose is commonly seen together with xylazine overdose. While the drug naloxone can reverse opioid overdose effects, it won’t do the same for xylazine. Missing a simultaneous opioid overdose can lead to severe, even deadly consequences.
• Benzodiazepine overdose can also result in symptoms similar to xylazine overdose, with less effect on breathing and heart rate.
• Other drugs that can mimic xylazine toxicity include barbiturates and ethyl alcohol.

Some other medications, if taken in too large of quantities, can also show up like a xylazine overdose. These medicines include:

• Drugs in the same group as xylazine, called alpha-2 adrenergic agonists, like clonidine, tizanidine, guanfacine, and dexmedetomidine.
• Heart medications like beta blockers and calcium channel blockers.

If someone uses xylazine, they may also have skin sores regardless of how they took the drug. It’s crucial to check other possible causes for the sores. Doctors will need to thoroughly investigate the patient’s medical history, do a complete physical exam, and possible even conduct tests on wound cultures, biopsy samples or do imaging studies. Possible causes of skin sores can include:

• Different infections, like bacterial cellulitis, necrotizing fasciitis, bullous impetigo, fungal skin diseases, and viral infections.
• Using other drugs like heroin or methamphetamine.
• Using cocaine that has been cut with a drug called levamisole can cause sores, frequently on the ears and nose.
• Chronic vein stasis, peripheral artery disease, poorly managed diabetes, vasculitides (blood vessel inflammation), and autoimmune diseases can result in sores.
• Rarely, pressure sores, a skin condition called pyoderma gangrenosum, and an advanced form of skin cancer called squamous cell carcinoma can also present as chronic, non-healing skin sores.

What to expect with Xylazine Toxicity

The use of a substance called xylazine in humans can lead to various health consequences. Many factors can impact how a person recovers from xylazine toxicity or poisoning. These factors include the amount of xylazine they have taken, if xylazine was mixed with other powerful painkillers called opioids, the individual’s general health condition, and how quickly medical help is received.

Recognizing the symptoms early and seeking medical help as soon as possible can massively affect the outcome. Swift medical intervention can help avoid serious complications like severe difficulty in breathing and improve the chances of a person recovering well. However, continuous exposure or use can lead to very severe health problems, even death.

Avoiding the use of xylazine is crucial. If someone has xylazine-induced skin ulcers, quick and appropriate treatment could lead to healing. However, if these ulcers are not properly taken care of and get infected, the risk of acquiring a body-wide infection known as sepsis increases significantly. This could further lead to complications like the requirement for a limb amputation and an increased risk of death.

Possible Complications When Diagnosed with Xylazine Toxicity

Taking too much xylazine, or being affected by its toxicity, can have significant health risks, even leading to death. The exact ways in which different parts of the body are affected are not well-studied in humans. However, some research on both humans and animals suggests that xylazine use can lead to severe health problems, like heart failure, fluid build-up in the lungs, heart muscle damage, heart valve problems, and diabetes that requires insulin for control.

The main compound that forms in the body when we break down xylazine, called 2,6-xylidine, can cause changes to our cells that might lead to cancer. People who use xylazine for an extended period may be at a higher risk of developing cancer. Some studies show that xylazine can increase short-living molecules, reactive oxygen species (ROS), in certain cells in the body, which can lead to DNA damage. More research is required to understand this process better, as it could potentially start or increase the likelihood of cancer.

There’s no information on how xylazine affects human pregnancies. However, veterinary studies have shown that in pregnant animals like cows and goats, xylazine can cause increased uterus contractions, decreased blood flow to the uterus, and loss of the fetus.

It’s also worth noting that addiction to xylazine can be stronger compared to addiction to opioids, including a strong opioid called fentanyl. Extended use of xylazine might lead to dependency, which can make it harder for people to stop using it. There are currently no effective treatments for people going through withdrawal from xylazine or for long-term xylazine addiction.

Possible risks from xylazine include:

• Heart failure
• Fluid build-up in the lungs
• Heart muscle damage
• Heart valve problems
• Insulin-dependent diabetes
• Cancer risk from the breakdown product 2,6-xylidine
• DNA damage
• Unknown effects on human pregnancy
• Increased uterus contractions, decreased uterus blood flow and possible fetus loss in animals
• Strong addiction potential, potentially stronger than opioids
• Lack of effective treatments for withdrawal or long-term addiction

Preventing Xylazine Toxicity

The rising issue of xylazine toxicity in humans is a growing concern in a time when substance abuse and related deaths are increasing. We need strategies to discourage people from misusing xylazine, and we also need to educate people about the risks involved.

Deterrence

Deterrence is a comprehensive and complex approach to prevent drug misuse. It involves law enforcement officers, health regulators, healthcare workers, and members of the community.

Law enforcement and regulators: It’s important to put robust measures in place to prevent the misuse of xylazine, including better monitoring, stricter punishments for illegal distribution, and global cooperation to prevent cross-border smuggling. Given the risk of misuse and the potential benefits of xylazine as an anesthetic in veterinary medicine, halting the production of this drug altogether could be beneficial. It might be worth exploring different anesthetics. Officials and policymakers can help establish safer supply programs to reduce people’s reliance on unregulated and dangerous drug supplies and accidental exposure to xylazine.

Healthcare professionals: Healthcare workers, especially veterinarians worldwide, have a key role to play in preventing drug misuse. This is because xylazine originally entered the human market from veterinary use, not illegal production. They can help identify and intervene in cases of substance misuse. Doctors can also help reduce addiction by checking patients for substance use disorders and quickly referring them to addiction treatment services.

Community members: Initiatives led by community members can significantly contribute to prevention efforts. That includes building awareness about the dangers of drug misuse, offering resources for safely disposing of unused veterinary drugs, and promoting community programs that educate potentially at-risk groups about xylazine and its dangers.

Patient Education

Besides deterrence, patient education is crucial in our fight against xylazine misuse and toxicity.

* Risks and consequences: Education about the dangers and potential outcomes of xylazine misuse is vital. This should cover health issues like breathing difficulties, addiction risk, low blood pressure, and fatal overdose. Importantly, people need to understand that xylazine is not designed for human use and its long-term effects on humans are unknown.

* Recognition of symptoms: It’s also important to educate people who might be at risk, including those who inject drugs, about the signs of xylazine toxicity. They need to understand the difference between feeling high and experiencing a depressed central nervous system, breathing difficulties, and low blood pressure. With proper education, they can recognize harmful effects in themselves or others sooner and get medical help more quickly during an overdose.

* Safe practices: Those who handle xylazine as part of their job should be educated about safely storing and disposing of it to prevent accidental exposure or misuse.

* Resources and support: People should be informed about where they can get help for addiction, including local addiction treatment services, support groups, and easy-to-use support apps.

Harm Reduction Strategies

If stopping drug use is not immediately possible, harm-reduction strategies can be discussed and suggested. Two crucial harm reduction approaches involve wound care and safer drug use. Wound care involves providing personal wound care supplies and guidance on safer drug use such as not injecting into wounds and not using drugs alone.

Healthcare agencies can also provide patients with clean syringes, training on how to administer naloxone (a medication used to reverse opioid overdose), and training on how to use and interpret the results of fentanyl (a potent opioid) test strips, as part of supervised consumption strategies.