There are few people across North America who are unaware of the ongoing opioid epidemic. In the late 1990s, due to perceived safety and pharmaceutical corporate influence, medical prescribing patterns for pain management shifted increasingly toward opioid use. By the 2010s, what was known as the “opioid public health crisis” had become a fully blown epidemic, affecting people of all socioeconomic classes, postal codes and ages across North America – killing almost 45,000 people in Canada in the last seven years.
Today, solutions to the epidemic remain complex, nuanced, debated, and sadly, politicized. While efforts revolve around recovery-oriented policy and effective harm reduction approaches, the emergence of a toxic drug supply has thrown a wrench into this policy debate. In March 2023, it was reported that 97 per cent of samples that drug-users believed were solely fentanyl were in fact laced with other substances. Adulterants in the illicit drug supply have become the major driver for the precipitous rise in fatal drug poisonings. Chief among these substances is xylazine, a potent alpha-2-adrenergic agonist (non-opioid tranquilizer) and clonidine analog first synthesized in 1962. Xylazine is usually found in the veterinary medicine field (namely for animals like cows and horses) where it is being used for its strong sedative, anesthetic and muscle relaxant effects. However, due to its severe central nervous system effects like profound stupor, decreased respiratory rate, slow heart rate and dangerously low blood pressure, the risk of overdose and death in humans is significantly high. For these reasons, xylazine continues not to be approved for human-use in North America.
If we hope to address this opioid epidemic, we must arm ourselves against adulterants like xylazine. In fact, Ontario’s Chief Medical Officer of Health report highlights that “when we see preventable threats, like substance use, that harm too many people too young, devastate families, destroy communities and reduce life expectancy, we must act.” Yet, here we are – with a new preventable, insidious threat right under our noses – and little to nothing being done.
Also known as “tranq” or “tranq-dope,” xylazine permeated the Canadian illicit drug supply in early 2019, initially in Alberta and British Columbia before quickly making its way to Ontario, where it has been found as a co-occurring substance, most notably with fentanyl. Three-quarters of Ontario samples submitted by law enforcement agencies for testing in 2022 contained xylazine.
The combination of xylazine and opioids further complicates response protocols. Although the symptoms of xylazine and opioids are similar, naloxone (Narcan) can only temporarily reverse opioid effects and has zero effect on xylazine, a non-opioid. While naloxone is still advised to address the opioid’s impacts, current guidelines only suggest supportive management for xylazine as there are no available pharmaceutical antidotes.
Xylazine is unknowingly consumed by users as those distributing unregulated opioid supplies are often combining it with other drugs to increase bulk (cost-cutting), increase addictive properties, and enhance/extend the effects of opioids. The opioid-user population is largely unaware of its presence and clinicians are not able to recognize its involvement due to similar symptomatology.
Importantly, recovery may also be further complicated for individuals who are seeking treatment as their reliance on substances now includes both opioids and xylazine since physical dependency and subsequent withdrawal also may result with repeated exposure of xylazine. Severe anxiety or agitation may occur with sudden cessation of drug mixtures containing xylazine, further undermining patients’ efforts to obtain appropriate treatment for concurrent opioid use disorder and perpetuate an individual’s dependence upon illicit drugs.
Recovery may also be further complicated for individuals who are seeking treatment as their reliance on substances now includes both opioids and xylazine.
With a problem as complex and multifaceted as the opioid epidemic, addressing this challenge is not something that can be done overnight or with a silver bullet. We are dealing with a poorly understood substance that has infiltrated the opioid supply at an alarming rate. To keep up, it is critically important to invest in a comprehensive strategy:
Increase Awareness Among Drug Users & Clinicians
Provide high-quality education around xylazine to individuals who use drugs – irrespective of their drug of choice. Besides xylazine prevalence, drug users should be aware of other essential information, for instance, that fentanyl test strips cannot detect xylazine. In other words, even if their fentanyl strips turn negative, the user’s drugs could have still been cut with xylazine.
Destigmatize adulterants. It is important to realize that most consumers of xylazine do it unknowingly. Blaming drug users will alienate them further. Moreover, the language we use has power. Referring to xylazine as a “zombie drug” (so called due to disfiguring, severe necrotic skin ulcerations that arise from its use, distinct from wounds associated with intravenous drug use) damages rapport with active drug-users, making them more unlikely to reach out for medical assistance.
Invest in Prevention Tools & Research
Prevention is key and to this effect, rapid test strips and other reliable point-of-care tests for biologic specimens and drugs must be implemented liberally across jurisdictions (xylazine test strips can be used for suspected laced drug samples). However, there is a need to evaluate their efficacy and accuracy before implementation in the community. Likewise, xylazine detection assays (to determine systemic xylazine absorption) should also be an investment priority.
Investment in the discovery of xylazine antagonists is essential. To date, there is no treatment or reversal agent for xylazine in humans. However, some drugs have been developed to reverse the drug’s effects within the veterinary population, namely atipamezole – an alpha-2-adrenergic antagonist. Studies have shown some preliminary effectiveness in reversing sedative and cardiovascular effects of alpha-2-agonists (like xylazine) in humans. If optimized for human physiology, atipamezole could become a key tool in addressing this growing problem – akin to naloxone’s role in the opioid epidemic.
System-wide Harm Reduction
Ultimately, the definitive solution for xylazine and other adulterants in the illicit drug supply remains a regulated, safer drug supply.
Unfortunately, the fact is that xylazine has found its way into the illicit drug supply and has the potential to bring the lives of tens of thousands of people crashing down if it is not addressed promptly. Furthermore, xylazine may serve as a foot-in-the-door substance for many new adulterants to come.
We must be proactive. We cannot afford to sit back and watch what happens to our friends and family. Indecision is indeed a decision, and in this case, it would be a decision to watch our fellow Canadians die when we could have saved so many.
Now is the time to act and stay ahead of this expanding syndemic.
