A Decade into the Fentanyl-death Crisis in Canada: Selected Insights and Implications for Strategic Paths Forward

INTRODUCTION Just over 10 years ago, synthetic, toxic opioids (STOs; ie, fentanyl and analogues) began to appear and quickly spread in Canada’s illicit drug supply.1,2 Their adverse consequences rapidly evolved into the country’s worst and persistent epidemic of drug overdose deaths (DOD) and related public health crisis. A decade into this crisis, some—mostly young and middle-aged—60,000 Canadians have died from a DOD, with yet the highest levels of DODs (8049 or 20.8/100,000) recorded in 2023; of these DODs, more than 80% were fentanyl-caused while approximately half also involved psychostimulants, which overall indicates a reality of poly-substance—and in many instances poly-toxicological—dynamics in play.1,3 Yet despite extensive efforts and resources invested overtime—and recent slight declines in DOD levels, the combined responses have overall proven to be insufficient to effectively address this crisis of tragic deaths and related suffering. Its sobering “silver anniversary” provides the opportunity for a few select basic insights and observations on the DOD crisis' essential characteristics and implications, with some possibly useful to inform or guide strategic paths and options forward. STOs are here to stay When STO drugs first appeared in the illicit drug supply and rapidly accelerated DOD levels, many of us thought—or quietly hoped—that this was a temporary phenomenon that would somehow resolve itself with things returning to prior “normals” in terms of the drugs and harm levels involved. Just a decade but tens of thousands of DODs later, it needs to be accepted that this has been an unrealistic expectation for several reasons. As one key factor, STO production is a relatively quick and simple process based on advanced technologies. It mainly relies on widely available chemical precursors that are independent of vulnerable agricultural crops and time-consuming processes; beyond, STOs' efficient production and multiple distribution modes translate into generous profit margins and related price-flexibility among illicit suppliers to accelerate demand.4,5 But STOs' “advantages” exceed production-related factors. Estimates suggest that fentanyl offers 100 times higher potency-per-cost unit—or “bang-for-the-buck”—than heroin, contributing to persistently high demand by its consumers.4,5 A somewhat similar shift of supply and use has occurred in the area of psychostimulants, where synthetic formulations (eg, methamphetamine) have replaced more traditional (eg, cocaine) products to a large extent while with amplified risks for harm outcomes, especially in socio-economically marginalized populations.6 All considered, STOs—and, similarly, other synthetic drug categories as noted—and the excessive harms their use produces, especially among the most vulnerable consumers, are foreseeably here to stay, and our drug policy and intervention systems must adapt and respond to these fundamentally new realities.5,7 STOs are no longer a “foreign”-made problem When the STO-driven DOD crisis began to evolve, a key element feeding the collective outrage arose from the perception that this problem met the classic “illicit drug” narrative: This, centrally, included that the STO drugs involved were illicitly produced in foreign countries (eg, China, Mexico) and subsequently shipped to and distributed by criminal networks in North America.5 This came as a welcome departure or perceived relief from the uncomfortable dynamics of the opioid crisis’ recently preceding (eg, pre-2012) chapter, where most DODs had been caused by opioid medications produced and/or prescribed—but commonly diverted—for medical use in Canada.8,9 But these assumed constellations of a foreign-made and supplied STO crisis do no longer appear to be correct. Rather, recent enforcement data suggest that large extents of the illicit fentanyl consumed in Canada has shifted in origin from supply imported from abroad to domestic production.10 While some of the precursors used may still be imported, domestic production appears to have become the major supply source for STOs available. Even more so, Canada has become an STO export nation, with recent seizures of fentanyl shipments to other countries (eg, the United States) reported to far outweigh the seizures of imports into Canada.10 Supply enforcement’s reach is highly constrained It is well-established that drug interdiction efforts only manage to detect and seize a miniscule proportion of illegal drug supply in circulation, and its capabilities to “dry up” a drug problem from the supply end are largely mute.11 These limited odds for enforcement's impact potential are even more adversely stacked in the case of STO production and distribution. While the occasional (even “super”) laboratory, based on extensive enforcement resources invested—and with related isolated “success” stories broadly showcased—will regularly be detected and shut down, this is not a realistically “winnable” fight against this formidably high-powered and flexible enemy.5,12 As an additional key factor, illicit fentanyl comes with exceptionally high drug potency compressed in the smallest amounts of unit-amounts. To illustrate: the fentanyl contained in a small, one-pound parcel is sufficient for 200,000 fentanyl pills or use episodes, and estimates suggest that the annual fentanyl consumption amount for the United States is in the single-digit metric tons, and fits into just a single transport truck or container13; the corresponding amounts for Canada would likely translate into a minor proportion of that. On this basis, even with far extended resources, supply enforcement efforts are most unlikely to eradicate, or even markedly disrupt STO production and markets beyond isolated symbolic “successes”; short of surrendering to these adverse dynamics, the extensive enforcement resources involved are likely better invested in reducing key market-related (eg, violence) harms and for the direct protection of the health and safety of drug consumers. Treatment is a universally desirable, useful but practically limited intervention There have been ample voices demanding (more) “treatment” as the primary intervention response to the STO crisis. Naturally, among those many embracing addiction as a chronic disease, this is an ultimately desirable perspective and proposition. But while evidence-supported treatments for opioid use disorder (OUD) exist, one must consider their reality-based limitations. For OUD, the basic “gold-standard” treatments include medication-assisted opioid agonist (eg, methadone-based/buprenorphine-based) treatments (OATs) which are well available in many parts of Canada, while in others, access is still limited and/or treatment approaches do not meet best practices.14,15 While generally considered “effective” for reducing adverse (eg, overdose-risk) outcomes compared with no treatment, OATs typically only engage half or less of individuals with OUD. Moreover, they retain only 20% to 50% of patients (eg, at 6–12 months post-initiation) entering OAT, with the rest disengaging from treatment; in addition, half or more of those retained continue involvement with nonmedical, commonly risky drug use that exposes them to overdose and other severe health risks.14–16 These limited and compromised treatment response outcomes for OAT are commonly amplified among individuals involved in fentanyl—compared with other opioid use.15,17 While some high-intensity (eg, injection opioid-based OAT) treatment modalities produce better rates of outcomes (eg, for retention or illicit drug use), these are resource-demanding “last resort” options for treatment available only to very limited patient sub-groups.18,19 Given that there is evidence that OAT remains comparably effective for DOD prevention among those minorities of individuals consistently treatment engaged even in contexts of common fentanyl use, the factors working against protective OAT engagement among the majority of others need to be better understood, and addressed.20 There have been increasing calls for alternative (eg, abstinence-oriented/recovery-oriented or compulsory) treatment approaches, but the evidence-based supporting their effectiveness is thin and/or equivocal; plus, they raise fundamental ethical and other concerns in regards to possible indirect adverse outcomes.21 At the same time, not all overdose deaths occur in individuals with previously established OUD and, therefore, outside of the reach of possibly protective treatment interventions.22,23 Overall, these dynamics in current realities mean that—even if optimally scaled up—presently available evidence-based treatments for OUD will only manage to effectively treat a limited minority of STO-involved individuals to a degree where these are reliably protected from STO use and related (eg, overdose) risks; this minority may be likely smaller than the number of newly initiated users. Treatment options for psychostimulants ought to be considered even more limited in availability and outcomes than those for OUD.6,24 In other words, while treatment interventions are an integral core component of the system response to the DOD crisis, we will not be able to universally “treat” ourselves out of the STO problem with a singular focus on treatment as the primary intervention response, even under further optimized conditions. “Harm reduction” measures—an important but also limited toolbox There is ample evidence that “harm reduction” measures [eg, supervised consumption/overdose prevention sites (SCS/OPS), naloxone distribution, drug checking] present a mostly effective intervention armory towards reducing the STO-related risk for DOD in instances where available and utilized; robust evidence has shown that these measures have resulted in a significant number of averted DODs.1,16,25 However, especially in contexts of the present STO-driven dynamics, “harm reduction” measures face—similar while natural—limitations as the evidence-based OUD treatments described, which likely render them not realistically capable of profoundly reduce DODs below current levels. Crucial reasons for this include the particular nature or design, but also the scalability of related interventions available. For example, while SCS/OPS are effective in preventing DODs in instances when utilized, and their availability has been substantially expanded across Canada, only a very limited subfraction of STO use episodes actually occur under their protective intervention umbrella.16,26 Naloxone is a solely reactive death prevention measure that requires an overdose to happen in conducive circumstances (eg, presence of a responder with naloxone ready for administration), while facing additional challenges from STOs unique pharmacology for effective reversal interventions to occur.27,28 The actual impacts of “drug checking” on effectively altering actual DOD risk or outcomes among drug consumers remain to be ascertained.29 Overall, there are substantial gaps, and there is extensive room for optimization in the availability and access of “harm reduction” measures, especially in select under-served parts of Canada which could contribute to decreasing DOD levels in these regions. Importantly, “harm reduction” and “treatment” measures are not mutually alternative but complementary interventions, yet neither—whether singularly or jointly—are realistically capable or sufficient by nature of their intrinsic limitations in reach and design-related effects to effectively resolve the presently excessive DOD burden on a population level. This has been tangibly shown in settings like BC with high and increasing intervention availability yet continuously increasing DOD rates for most of the past decade. CONCLUSIONS The continuous STO-driven DOD crisis presents a paradigmatically new reality for drug problems, including profound consequential challenges for policy and intervention design and delivery; these dynamics will likely remain or even intensify for the foreseeable future. The decade-old STO crisis has tangibly demonstrated that currently available—for example, evidence-based harm reduction and treatment—intervention responses have been limited in their remedial impact and insufficient to significantly curb and address this problem, even in settings where widely established and available.1,25 Going forward, the realistically best response approach to the STO crisis in the short- or mid-term will likely come from a complementary and well-coordinated “patchwork” approach of delivering, optimizing, and scaling up available evidence-based (eg, harm reduction, treatment) interventions as far as possible; there are parts of Canada for which there is extensive room and needs to do so. A recently new while, possibly valuable, additional intervention element comes in the form of “safer opioid supply” (SOS) measures, which provide alternative medication-grade opioid products to those individuals acutely involved in STO use and at related risk for DOD. While work remains to be done toward the optimization of the design and delivery modes (eg, through community-based while observed distribution to minimize diversion as a main collateral risk) and appropriate scale-up of SOS measures, emerging evidence suggests SOS measures' potential to reduce STO exposure and DOD-risk among certain high-risk participants for benefits.30,31 As is well-known, the DOD crisis is characterized by other key factors and determinants, such as common severe (eg, mental health) comorbidities and socio-economic (eg, rehousing) disenfranchisement—amplified by the adverse effects of drug use criminalization—among its victims that require sustained, effective solutions. Direly needed intervention efforts to effectively combat the acute STO-driven DOD crisis will not effectively occur with narrow focus on a singular strategy, but presumably produce realistically best possible impacts by utilizing and optimizing the combined potential across the available spectrum of evidence-supported interventions.1,5 These interventions ought to actively address the prevalent co-morbidities (eg, mental health, pain) that commonly co-occur with problematic, high-risk substance use. Even if done so, based on the natural limitations of the interventions described, this approach ought not to be expected to produce miracle solutions; however, it is the realistically most likely path to finally bending the curve and achieving tangible reductions of the DOD-epidemic’s tragic death toll as it is advancing its second decade. Toward long-term solutions, radical rethinking will likely be required to prevent the persistence or recurrence of similar crisis. This, on the one hand, will likely need to rely much more on social investments and specifically addressing the upstream social determinants of health (eg, housing, poverty) that contribute to harmful substance use, especially among marginalized populations, for improved prevention and population health outcomes.32,33 At the same time, also given the challenging dynamics of new synthetic substances and the natural limitations of post hoc- and primarily behavior change-based (eg, harm reduction, treatment) interventions for curtailing related harm, fundamentally alternative perspectives and control paradigms (eg, regulated drug availability) for psychoactive substance use and related risk populations may need to be collectively discussed and considered for development and implementation.34

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