Benzodiazepines and xylazine: effects and harms of sedatives in the unregulated drug supply

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Benzodiazepines and xylazine have begun appearing unexpectedly in unregulated drugs, particularly fentanyl, and are causing multiple health concerns. Increased understanding of this situation and related health issues can help service providers to respond and reduce harms.

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What are benzodiazepines and xylazine?

Benzodiazepines are sedatives that slow the body down. They produce feelings of calm, muscle relaxation and sleepiness.1,2 Benzodiazepines are prescribed to treat anxiety, sleep and seizure disorders, to manage alcohol withdrawal and to cause sedation for some medical procedures.1,2 Side effects of benzodiazepines vary by dose and include symptoms such as dizziness, challenges with learning, memory loss, reduced breathing and hallucinations.1

Medical benzodiazepines are very commonly prescribed and include lorazepam (Ativan), alprazolam (Xanax) and diazepam (Valium). Most benzodiazepines found in the unregulated drug supply are non-medical benzodiazepines, such as etizolam, flualprazolam and bromazolam.2 The term non-medical benzodiazepines refers to benzodiazepines and benzodiazepine-like substances that have been illegally produced or diverted from legal sources.2 Many non-medical benzodiazepines have not been licensed for use in Canada and have never been tested on humans or animals.2

Xylazine was originally developed to treat high blood pressure.3 However, it was found to cause excessive sedation and was not approved for human use.3 Xylazine is now used by veterinarians as a sedative and muscle relaxant.3

In humans, available evidence indicates that xylazine slows the body down and can cause muscle relaxation and sedation and can reduce pain.4 It also appears to be associated with a wide range of side effects, including reduced breathing, cardiovascular effects (e.g., low blood pressure, low heart rate, constricted blood vessels) and other effects (e.g., high blood sugar, reduced bladder control).3–6

Where and in what drugs are benzodiazepines and xylazine being detected?

Available evidence can provide insight into large-scale trends and patterns related to benzodiazepines and xylazine in Canada’s unregulated drug supply. However, the majority of communities do not have access to comprehensive and timely monitoring of the unregulated drug supply (e.g., drug checking programs, wastewater monitoring, data from toxicology laboratories). This makes it challenging to monitor the presence, type(s), and prevalence of sedatives in each local unregulated drug supply.

Multiple types of non-medical benzodiazepines have been detected in the unregulated drug supply in Canada since at least 2018.2,7 In testing data from law enforcement drug seizures in 2021, benzodiazepines were most commonly detected with opioids such as fentanyl (60.7%; sometimes called benzodope), but also alone (27.8%) and occasionally with stimulants (5.4%).2 Their prevalence in the unregulated supply increased rapidly in certain regions during the COVID-19 pandemic.8 Data from 2021 indicate that it was most common for unregulated opioids to contain benzodiazepines in Ontario, British Columbia and Alberta, although benzodiazepines have been detected with opioids in several other provinces and territories.2

Xylazine emerged as a concern in Canada’s unregulated drug supply in 2019. While it remains relatively uncommon in most of Canada, its prevalence increased rapidly in 2021 and 2022.4 Xylazine is mostly detected with other drugs, in particular fentanyl (sometimes called tranqdope). Of drugs seized by law enforcement between May 2022 and April 2023, 99% of samples with xylazine also contained fentanyl and 52% contained both fentanyl and benzodiazepines.9 Over the same period, xylazine was very rarely detected with stimulants (0.3% of samples containing methamphetamine, 0.2% of samples containing cocaine).9 As of April 2023, xylazine has been detected in nine provinces or territories, most commonly in Ontario, British Columbia, Alberta and Quebec.4

Why are benzodiazepines and xylazine being found in the unregulated drug supply?

There are a number of potential reasons why benzodiazepines and xylazine might be added to opioids in the unregulated drug supply, including the following:

  • Benzodiazepines and xylazine can mimic the effects of fentanyl and can add more bulk or weight to the drugs. This can allow for less fentanyl to be used in production and can reduce costs.4,8,10
  • Benzodiazepines and xylazine are long-acting drugs: effects can last from seven to 15 hours for benzodiazepines and for eight to 72 hours for xylazine.2,5,10 When added to fentanyl, they can extend and enhance its effects, masking fentanyl’s short (30 minutes to an hour) duration of action.3,4,10,11

Some people enjoy the effects of benzodope and/or tranqdope. The presence of benzodiazepines and/or xylazine can allow some people to avoid opioid withdrawal for longer and use drugs less frequently, saving money.10 For others, the presence of sedatives is undesirable because of the potential for increased harms.

The addition of sedatives to opioids is occurring within the context of broader changes to the unregulated drug supply. These changes have seen synthetic drugs become more dominant, displacing drugs made with organic materials in the market (e.g., fentanyl displacing heroin, methamphetamine displacing cocaine).10,12 Prohibition laws and policies are a key factor in the arrival of sedatives. This is because prohibition has resulted in a harmful lack of oversight of the contents and quality of substances that people consume and has enabled the growth of an unregulated market that is incentivized to produce smaller and stronger drugs to reduce costs and increase profits.10,13,14

Are benzodiazepines and xylazine increasing the risk of drug toxicity death?

Fentanyl remains the primary driver of drug toxicity deaths in Canada.15 It is unclear whether the addition of benzodiazepines and/or xylazine to opioids in the unregulated drug supply is directly contributing to an increased risk of drug toxicity death. Concerns have been raised about their potential to increase risk of drug toxicity death for several reasons:

  • When sedatives and opioids are consumed at the same time, drug interactions may cause the combined effects (e.g., with respect to reduced breathing) to be greater than those from either drug alone. This could increase the risk of death.2
  • When individuals consume sedatives and opioids at the same time, it can be more complicated to respond to overdose or drug toxicity.2 This is because benzodiazepines and xylazine can cause people to stay sedated or unconscious even after they have been given naloxone to reverse their opioid overdose and their breathing has returned to normal.
  • Benzodiazepines have been detected in a significant proportion of drug toxicity deaths in Canada.16–18 Xylazine has been detected in a growing proportion of drug toxicity deaths in the United States, nearly always combined with fentanyl.9,19

However, the variable potency of sedatives and opioids in the unregulated drug supply makes it challenging to determine whether sedatives are increasing the risk of death. Sedatives may be detected when a person experiences drug toxicity, but the amount and potency — alone or in combination with opioids — may not be enough to have contributed to the overdose.20 For example, in Ontario, the proportion of drug toxicity deaths where benzodiazepines were determined to have directly contributed to the death is much lower than the proportion of those deaths in which these drugs were detected.17,18 As of April 2023, xylazine had not been reported to have directly contributed to a death in Canada.9 Further research is needed to better understand how xylazine and benzodiazepines are affecting people’s risk of drug toxicity deaths.

What are the health effects of benzodiazepines and xylazine in the unregulated drug supply?

The evidence suggests that benzodiazepines and xylazine in the unregulated drug supply are causing significant harms for people who use drugs.

Prolonged sedation

Xylazine and benzodiazepines can cause prolonged sedation, which means that people remain sedated or unconscious for extended periods.3,8 This can cause harm in a number of ways, including the following:

  • People’s vulnerability to theft, physical assault and sexual assault is increased due to extended periods of sedation or unconsciousness.2,3,8,21
  • People have “blackouts” where they lose track of time and cannot remember their actions (only associated with benzodiazepines).2,8,21 Blackouts may cause people to take risks that they otherwise would not take and can leave them vulnerable to theft, physical and sexual assault.8
  • People may remain in awkward body positions (e.g., positions that reduce blood circulation) for long periods or in harmful environments (e.g., outdoors in the cold or in the sun).2,3 This can increase risk of harms such as pressure ulcers, frostbite and heatstroke.3

Prolonged sedation can also complicate responses to drug toxicity and can be challenging for responders to manage in both community and service settings. For example, supervised consumption services (SCS) and overdose prevention sites (OPS) have not been designed to provide ongoing support to people experiencing prolonged sedation. In addition, other potential medical emergencies (e.g., low blood sugar) may be mistaken for prolonged sedation.

Tolerance and withdrawal

Using drugs containing xylazine and/or benzodiazepines, intentionally or unintentionally, can lead people to develop tolerance to these drugs.8,22 Tolerance to benzodiazepines can develop quickly — in as little as four weeks of regular use.2 It is unclear how long it takes to develop tolerance to xylazine. If people’s consumption of sedatives in unregulated drugs decreases for any reason (e.g., changes in the unregulated supply, accessing treatment for substance use disorder, being incarcerated), they may unexpectedly experience withdrawal from benzodiazepines and/or xylazine.

Withdrawal symptoms are as follows:

  • Benzodiazepine withdrawal symptoms include anxiety, nausea, reduced appetite, diarrhea, confusion, disorientation, hallucinations and seizures, and they can be fatal.8,23,24
  • Xylazine withdrawal is not yet well understood. Symptoms are reported to be severe and can involve irritability, anxiety, headaches, rapid heart rate and high blood pressure.10,22,25

Benzodiazepine withdrawal can be life-threatening and requires medical support from healthcare providers to manage.23,24 While less is known about xylazine withdrawal, healthcare providers can also provide supports to manage xylazine withdrawal symptoms.26

Xylazine-related wounds

Xylazine has been associated with distinct skin wounds. Among people who use drugs, wounds are usually caused by bacteria getting into to the body while injecting. They are commonly found at or near the injection site. In contrast, xylazine-related wounds can appear in places that have not been used to inject3,5 and can appear among people who do not inject their drugs.22 It is not yet known why xylazine causes wounds, but some propose that it may be due to xylazine’s effects on the circulatory system3,5,22 or suspect that xylazine may damage tissues in the skin.27

Xylazine-related wounds can vary in appearance but often: 3,5

  • cover a large surface area (greater than 10 cm across)
  • resemble burns or ulcers
  • appear first as small “punch hole” wounds in a cluster, then come together to form a larger wound
  • show signs of necrosis (tissue death) at the centre of the wound (e.g., redness, blisters, grey liquid draining from wound, black tissue)
  • appear quickly and get worse more quickly than other wounds

Medical care is usually needed to treat these wounds. More research is needed to understand why xylazine is causing such distinct and complicated wounds.22

Implications for service providers and policy makers

Service providers should be aware of and prepared for sedatives in their community’s unregulated drug supply. Responses can involve providing education, adapting programs and services to address emerging needs, and advocating for and changing policies to reduce harms.

Education can include the following topics:

  • The contents of the local unregulated drug supply. This can include information from drug checking about changes to the contents and/or potency of drugs and information from people who use drugs about notable or unexpected effects of drugs.
  • Potential harms and signs to watch out for (e.g., prolonged sedation, blackouts, appearance of strange wounds) with people who use drugs and their networks. Avoiding sensationalist or fear-based messaging around changes to the unregulated drug supply is important as these approaches can compound stigmas against people who use drugs.
  • How to access and use benzodiazepine and xylazine test strips, as well as their limitations. Test strips are not 100% reliable and can only provide information about whether a particular drug is present or not. For example, they cannot indicate how much of the drug is present, they cannot detect all types of benzodiazepines and they cannot detect xylazine in very small quantities.28,29
  • How to respond to overdoses with prolonged sedation, including prioritizing rescue breaths every five seconds and giving naloxone. Naloxone should be given every three to five minutes until the person’s breathing has been restored to normal (at least 10 breaths per minute and no choking or gurgling sounds).
  • How to support someone experiencing prolonged sedation. This can include making sure that they are not experiencing another medical emergency, they are not in a strange position, and their joints and airway are supported; laying them on a smooth surface; turning them over at least every two hours; and making sure they stay warm and dry.3
  • Strategies for safer substance use that may reduce people’s vulnerability to assault, theft, and other harms due to prolonged sedation. These could include encouraging people to use with someone they trust and to use at an SCS or OPS, if one is available.
  • Safer injecting and substance use practices. For xylazine, this may involve avoiding subcutaneous or intramuscular injections, if possible. When injecting xylazine, care should be taken to ensure the needle is in the vein to prevent xylazine from leaking into the surrounding muscle or tissue. This may reduce the risk of wounds.6
  • Information for people who use drugs about wound care and signs that a wound needs medical attention. Xylazine-related wounds have been associated with increased stigma and discrimination by healthcare providers, which creates barriers to care.21 It is important to discuss wounds and wound care in a non-judgmental, harm reduction-oriented approach.3 Discussions can include strategies to help keep wounds clean and covered, strategies to help avoid injecting into or near wounds, and signs that wounds are getting worse.3,27
  • Information for healthcare providers about caring for xylazine wounds. The severe appearance of xylazine-related wounds should not be assumed to mean that they cannot be treated or that extreme measures such as amputation are needed.3 Treatment for xylazine wounds is not yet standardized but steps include changing dressings frequently, using clean, moist bandages and keeping open wounds covered.27

Program-level responses can include the following:

  • Adapting organizational policies to respond to prolonged sedation. This could include increasing staffing levels, adjusting operating hours and developing partnerships with other services to ensure that continuing care is always available for people experiencing prolonged sedation.
  • Adapting organizational procedures to respond to prolonged sedation. This could include creating guidelines with steps for evaluating individuals to ensure that they are not experiencing other medical emergencies (e.g., head injury, high or low blood sugar). It could also include ensuring that equipment and guidance are available to provide care to people who are experiencing prolonged sedation (e.g., by monitoring oxygen levels, placing people on mats with their heads supported, regularly turning them over, keeping their possessions safe).
  • Providing access to drug checking services. For organizations without access to drug checking machines, this could involve distributing test strips and partnering with local or regional organizations that do have drug checking machines.30
  • Supporting people to access low-barrier, non-stigmatizing wound care. This can include integrating nurses with expertise in wound care in community settings, providing people with consistent access to wound care supplies (e.g., through outreach and onsite) and implementing multidisciplinary care teams to support people to engage in hospital-based treatment for wounds, when necessary.3,27
  • Developing and implementing policies and procedures for recognizing and managing withdrawal symptoms from sedatives in opioid agonist therapy (OAT), injectable OAT (iOAT), other treatment programs and safer supply programs. Guidance exists for managing withdrawal from benzodiazepines,23,24 but less is known about treating xylazine withdrawal.26 The perspectives and needs of people who use drugs should be centred in the development and implementation of these policies and procedures.

Policy-level responses can include the following:

  • Providing funding to expand access to drug checking services. Drug checking can help people to make decisions about their drug use, inform responses to benzodiazepines and/or xylazine in the unregulated drug supply, and monitor the unregulated drug supply for future contaminants.21
  • Providing funding to expand access to OAT, iOAT and safer supply.2 These services provide people with pharmaceutical alternatives to the unregulated drug supply and can play a crucial role in reducing people’s exposure to non-medical benzodiazepines and xylazine.
  • Addressing the factors that underly the toxic and unpredictable drug supply. This could include exploring alternatives to prohibition laws and policies (e.g., public health approaches to the regulation of currently illegal drugs).
  • Addressing underlying social and structural factors that increase the vulnerability of people who use drugs. For example, access to safe housing can prevent people from having to use outdoors or in situations that would put them at increased risk if they were to experience prolonged sedation.

Related resources

References

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Externally reviewed by: Steph Beaumont, Lachlyn Habermehl, Doris Payer & Samantha King

Production of this article has been made possible through a financial contribution from Health Canada's Substance Use and Addictions Program. The views expressed herein do not necessarily represent the views of Health Canada.

 

 

About the author(s)

Magnus Nowell is CATIE’s knowledge specialist in harm reduction. Magnus has previously worked in harm reduction research, community organizing and housing. He has a master’s degree in health promotion.