is a 3rd-year medical student at Touro College of Osteopathic Medicine in New York, NY, USA.

Nazanin Izadi, HBSc

Fentanyl and fentanyl analogues, such as carfentanil, are driving an opioid overdose crisis in North America.

 In 2019 alone, there were 3831 opioid-related deaths in Canada

 and 47,600 fatalities involving opioids in the United States (

 The COVID-19 pandemic has only heightened the tragic impact of opioids on individuals who use the drugs, on their families, and on communities across both countries.

National Overdose Deaths Involving Any Opioid

 are needed for this complex problem, and efforts are already underway. To mitigate the overdose crisis, both Canada and the United States have implemented multiple public health and treatment strategies. Extant strategies include providing opioid agonist therapies (OAT), naloxone for reversing fatal opioid overdoses, and access to harm-reduction services. In addition, injectable/implantable buprenorphine is available in both countries. However, the opioid receptor 

, while available in the oral formulation in both Canada and the United States, is not available in the depot formulation in Canada. Currently, OAT with methadone or buprenorphine/naloxone are the first-line interventions for individuals with moderate-to-severe opioid use disorder (OUD).

 is preferred over methadone for its superior safety profile, these treatments have many limitations. Moreover, in Canada, there are barriers to accessing OAT, including reduced access to OAT prescribers in rural areas and a shortage of pharmacies that offer on-site OAT.

OAT clinics often lack psychosocial supports and, frequently, high out-of-pocket expenses prove problematic for individuals with OUD who have limited financial means.

 Similar economic, geographic, attitudinal, and organizational barriers exist in the United States.

 Additionally, in the United States, where public insurance providers favor methadone whereas private insurance providers favor buprenorphine/naloxone, health insurance barriers have caused rampant racial and economic disparities in OAT access across the country.

, Canada has taken several novel harm-reduction approaches to combat it. Harm reduction refers to a wide array of public health policies intended to reduce the adverse consequences of human behaviors, including, but not limited to, substance use. In the context of the opioid crisis, harm-reduction interventions have included rapid-access addiction medicine services, provision of take-home naloxone kits, supervised consumption facilities (SCFs), and education around overdose risk mitigation.

Historically, the success of harm-reduction services for OUD has been difficult to quantify; most studies have small sample sizes and poorly defined outcome measures. These studies have limited generalizability to most individuals with OUD, who respond to first-line treatments. However, mounting evidence demonstrates proof of efficacy and effectiveness for a range of harm-reduction services. Recent studies have shown that they can reduce opioid overdose mortality, infection-related complications, and crime commitment among individuals with treatment-refractory OUD (TR-OUD).

In recent years, Canadian health care providers have implemented 3 critical harm-reduction measures that have curtailed opioid-related fatalities: (1) heroin-assisted treatment (HAT), (2) hydromorphone-assisted therapy, and (3) SCFs. 

 provides a summary of each of these novel treatments.

 A Comparison of 3 Novel Harm Reduction Methods to Address the Opioid Crisis

We advocate for the provision of substantiated harm-reduction services in the United States that, following the Canadian example, could save countless lives by increasing access to evidence-based treatment options for OUD.

HAT, or heroin maintenance, is an evidence-based intervention for managing the symptoms of TR-OUD. Although definitions of TR-OUD vary, most studies refer to the failure to respond meaningfully to 1 or more first-line treatments for OUD (eg, methadone or buprenorphine/suboxone). HAT is available in Canada (eg, Vancouver and Montreal) and some European countries (eg, Germany, Switzerland, and the United Kingdom) and has shown efficacy in select groups experiencing TR-OUD. To receive HAT, individuals with TR-OUD visit a designated HAT clinic, where they receive injectable medical-grade heroin (diacetylmorphine) up to 3 times daily under strict nursing and medical supervision.

 In essence, most HAT clinics operate under a supervised consumption model.

Results from randomized controlled trials have shown promising findings for individuals with TR-OUD. In one trial, HAT reduced illicit heroin use, improved treatment retention, reduced criminal activities, and improved mental and physical health compared with methadone therapy.

 While HAT is more expensive than oral methadone treatment, the social and economic benefits justify its provision for select patients with TR-OUD who have not benefited from first-line therapies. Nonetheless, studies have shown an association between HAT and a higher risk of adverse events such as seizures and opioid overdoses

. Although HAT carries a more dangerous safety profile than other forms of OAT, HAT administration typically occurs in supervised clinical settings, which lessens these risks. Thus, while HAT carries an increased absolute risk of adverse events—including opioid overdose—it is still a harm-reduction measure as it lessens the risk relative to the unsupervised consumption of street-sourced heroin or fentanyl.

Given the regulatory restrictions in providing HAT, investigators in Vancouver, British Columbia, considered alternative strategies for treating individuals with TR-OUD. The search for alternative OAT led to hydromorphone, a synthetic opioid used to treat chronic pain. Consequently, researchers at St Paul’s Hospital in Vancouver conducted the Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) trial.

In brief, the SALOME trial was an innovative study investigating the use of injectable hydromorphone (IH) as an alternative to intravenous diacetylmorphine (eg, HAT) for TR-OUD. The researchers aimed to establish the noninferiority of IH to HAT. Ultimately, the researchers found that delivering the 2 interventions under the same conditions (eg, supervised consumption facilities) led to positive outcomes in both groups. For example, participants receiving either treatment showed improved treatment retention, greater global functioning, reduced illicit opioid use, and diminished illegal activities.

 The SALOME trial was among the first to establish the efficacy of these harm-reduction measures for individuals with TR-OUD. Consequently, the SALOME trial results suggest that when diacetylmorphine is unavailable or other treatments are unsuccessful, IH can be a suitable alternative for treating severe TR-OUD.

In January 2019, Vancouver started the first hydromorphone tablet distribution program, based on the SALOME trial’s promising results. A qualitative study evaluated the program’s effects suggested that it can decrease illicit drug use, 

, and engagement in illegal activities, and can help address social inequalities surrounding drug use.

 Currently, in response to the COVID-19 pandemic and rising overdoses, take-home hydromorphone has been permitted, and the effects of this expansion can be promising for the widescale implementation of similar programs in rural, suburban, and urban settings.

 However, further study of injectable and oral hydromorphone in patients with TR-OUD in diverse settings is warranted.

 (SCFs) are safe, clean, indoor facilities where individuals can use preobtained drugs under the supervision of trained medical professionals to ensure safe injection or consumption by other methods (eg, oral or smoked). SCFs can implement rapid responses in cases of opioid overdoses, such as by providing intranasal or intramuscular naloxone.

 In recent years, mobile or pop-up SCFs have emerged in Toronto, Ottawa, Halifax, and other Canadian cities; these have been grassroots initiatives to address the unmet needs of special populations with TR-OUD or other substance use disorders. SCF initiatives can also offer assistance by providing counseling and psychosocial supports, referrals to social services, and access to medical and psychiatric treatment as necessary.

SCFs were first developed in response to the HIV epidemic in Vancouver when Insite—North America’s first SCF—proved to be a tremendous asset in combating the opioid crisis.

 SCFs also provides a multifaceted opportunity to address comorbidities, such as psychiatric illness, HIV/AIDS, and other infectious diseases. Because individuals with TR-OUD frequently experience co-occurring medical and psychiatric disorders, SCFs have created critical opportunities to engage with a population that can be otherwise difficult to reach. Studies have demonstrated the myriad benefits of SCFs, such as decreasing rates of overdose deaths, crime, and infectious disease transmission, while remaining cost-effective.

A recent study estimated the cost and impact of establishing SCFs in New York City. The results showed that an SCF could prevent 19 to 37 opioid overdose fatalities per year in that city, and save its health care system between $831,700 and $2.9 million as well.

 However, the establishment of SCFs remains controversial in the United States, and advocacy for drug policy changes must continue.

 has negatively affected all Canadian provinces and territories, with British Columbia, Ontario, and Alberta recording the highest number of opioid-related overdose deaths in 2019.

 The United States has also seen a widespread increase in the number of opioid-related deaths since the 2000s, with the northeastern, mid-Atlantic, and midwestern states being most affected.

 Currently, most of the overdose fatalities involve synthetic opioids such as fentanyl and its analogues,

 and most overdoses (more than 90%) appear to be accidental. The high prevalence of fentanyl as an adulterant in the illegal supplies of heroin and other injectable drugs (eg, cocaine and crystal methamphetamine) are the major factors accounting for the growing number of overdose-related deaths.

The rising number of opioid-related fatalities is a call to action to implement sustainable measures to prevent overdose occurrences beyond acute naloxone administration. Canada has implemented multiple harm-reduction measures since the beginning of its opioid crisis, which have reduced overdose mortality. For example, the current safe-supply programs focus on prescribing pharmaceutical-grade opioids, such as injectable hydromorphone and diacetylmorphine, to individuals who are at high risk of opioid overdose. This strategy is powerful in reducing the harms caused by fentanyl-related opioids on the illicit drug market, and as a result, overdose events have been prevented and overdose mortality has been decreased.

 Canadian and international studies on SCF have shown that the facilities are effective in reducing overdose fatalities, needle sharing, unsafe injection practices, and involvement in criminal activities.

As Canada and the United States seek comprehensive, collaborative, and evidence-based approaches to combat the current opioid crisis, they each can learn from the collective expertise and strategies implemented on the other side of the border.

is a third-year medical student at Touro College of Osteopathic Medicine in New York. 

is a fellow in addiction psychiatry at the University of Calgary’s Cumming School of Medicine.

is a staff psychiatrist in the addictions division at the Centre for Addiction and Mental Health (CAMH) and a lecturer in psychiatry, Temerty Faculty of Medicine, University of Toronto.

is an advanced practice clinical leader at CAMH, and a PhD candidate in the Bloomberg School of Nursing at the University of Toronto.

is professor of anthropology and psychiatry, and research chair in the social medicine theme, at UCLA’s David Geffen School of Medicine, Los Angeles.

is professor of psychiatry in the Temerty Faculty of Medicine at the University of Toronto and a clinician-scientist in the addictions division of CAMH in Toronto. He also serves as deputy editor of the journal Neuropsychopharmacology.

Acknowledgments - The constructive and critical comments of Eric C. Strain, MD, of John Hopkins University on the manuscript are gratefully acknowledged.

1. Ivsins A, Boyd J, Beletsky L, McNeil R. 

Tackling the overdose crisis: the role of safe supply.

2. Opioid- and stimulant-related harms in Canada [maps]. Government of Canada. June 2021. Accessed July 22, 2021. 

https://health-infobase.canada.ca/substance-related-harms/opioids-stimulants/maps

3. Overdose death rates. National Institute on Drug Abuse. Updated January 29, 2021. July 22, 2021. 

https://www.drugabuse.gov/drug-topics/trends-statistics/overdose-death-rates

4. Opioid- and stimulant-related harms in Canada [key findings]. Government of Canada. Updated June 2021. Accessed July 22, 2021. 

https://health-infobase.canada.ca/substance-related-harms/opioids-stimulants

5. Overdose deaths accelerating during COVID-19. News release. CDC; December 17, 2020. Accessed July 22, 2021. 

https://www.cdc.gov/media/releases/2020/p1218-overdose-deaths-covid-19.html

7. Priest KC, Gorfinkel L, Klimas J, et al. 

Comparing Canadian and the United States opioid agonist therapy policies.

8. Hansen HB, Siegel CE, Case BG, et al. 

Variation in buprenorphine and methadone treatment by racial, ethnic, and income characteristics of residential social areas in New York City.

Expanding supervised injection facilities across Canada: lessons from the Vancouver experience.

10. Heroin-assisted treatment (HAT). Drug Policy Alliance. February 2016. Accessed July 22, 2021. 

https://drugpolicy.org/sites/default/files/DPA%20Fact%20Sheet_Heroin-Assisted%20Treatment_(Feb.%202016).pdf

11. Oviedo-Joekes E, Brissette S, Marsh DC, et al. 

Diacetylmorphine versus methadone to treat opioid addiction.

12. Oviedo-Joekes E, Guh D, Brissette S, et al. 

Hydromorphone compared with diacetylmorphine for long-term opioid dependence: a randomized clinical trial.

13. Timko C, Schultz NR, Cucciare MA, et al. 

Retention in medication-assisted treatment for opiate dependence: a systematic review.

“It’s helped me a lot, just like to stay alive”: a qualitative analysis of outcomes of a novel hydromorphone tablet distribution program in Vancouver, Canada.

15. Behrends CN, Paone D, Nolan ML, et al. 

Estimated impact of supervised injection facilities on overdose fatalities and healthcare costs in New York City.

Articles

Harnessing Harm-Reduction Methods to Combat the Opioid Crisis

North America is currently experiencing an opioid overdose crisis driven mainly by fentanyl and fentanyl analogs, such as carfentanyl.

fatalities involving opioids in the United States

 The COVID-19 pandemic has only heightened the 

 of opioids on individuals who use the drugs, their families, and communities across 

 Novel solutions are needed for this complex problem.

Much is already being done. In an effort to mitigate the overdose crisis, both Canada and the United States have implemented multiple public health and treatment strategies. Extant strategies include providing opioid agonist therapies (OAT), naloxone for reversing fatal opioid overdoses, and access to harm reduction services. In addition, injectable/implantable buprenorphine is available in both countries. However, the opioid receptor antagonist naltrexone, while available in the oral formulation in both Canada and the United States, is not available in the depot formulation in Canada. Currently, OAT with methadone or buprenorphine/naloxone are the first-line interventions for individuals with moderate to severe 

 Although buprenorphine/naloxone is preferable over methadone in terms of its superior safety profile, there are many limitations to these treatments. Moreover, in Canada, there are barriers to accessing OAT, including reduced access to OAT prescribers in rural areas, and the shortage of pharmacies offering on-site OAT.

OAT clinics often lack psychosocial supports, and there are often high out-of-pocket expenses that prove problematic for individuals with OUD who have limited financial means.

 Additionally, in the United States, health insurance barriers, where public insurance providers favour methadone while private insurance favours buprenorphine/

, have caused rampant racial and economic disparities in OAT access across the United States.

Since the start of the opioid crisis, Canada has taken several novel harm reduction approaches to combat the opioid crisis. Harm reduction refers to a wide array of public health policies intended to reduce the adverse consequences of human behaviours, including—but not limited to—substance use. In the context of the opioid crisis, harm reduction interventions have included rapid access addiction medicine services, providing take-home naloxone kits, supervised consumption facilities (SCFs), and education around overdose risk mitigation.

Historically, the success of harm reduction services for OUD has been difficult to quantify; most studies have small sample sizes and poorly defined outcome measures. These studies have limited generalizability to most individuals with OUD, who respond to first-line treatments. However, there is mounting evidence that demonstrates proof of efficacy and effectiveness for a range of harm reduction services. Recent studies have shown that they can reduce opioid overdose mortality, infection-related complications, and crime amongst individuals with treatment-refractory OUD (TR-OUD).

In recent years the Canadian health care providers have implemented 3 critical harm reduction measures that have curtailed opioid-related fatalities: (1) heroin-assisted therapy, (2) hydromorphone-assisted therapy, and (3) supervised consumption facilities (SCFs). A summary of each of these novel treatments is provided in 

Table 1: A Comparison of 3 Novel Harm Reduction Methods to Address the Opioid Crisis

Following the Canadian example, we advocate for the provision of 

 in the United States that could save countless lives by increasing access to evidence-based treatment options for OUD.

Heroin-assisted treatment (HAT), or heroin maintenance, is an evidence-based intervention for managing the symptoms of treatment-refractory OUD (TR-OUD). While there are varying definitions of TR-OUD, most studies refer to the failure to respond meaningfully to 1 or more first-line treatments for OUD (eg, methadone or buprenorphine/suboxone). HAT is available in Canada (eg, Vancouver and Montreal) and in some European countries (eg, Germany, Switzerland, and the United Kingdom) and has shown efficacy in select groups experiencing TR-OUD. To receive HAT, individuals with TR-OUD must visit designated 

, where they will receive injectable medical-grade heroin (diacetylmorphine) up to 3 times daily under strict nursing and medical supervision.

 While HAT is more expensive than oral methadone treatment, the social and economic benefits justify its provision for select patients with TR-OUD who have not benefited from first-line therapies. Nonetheless, studies have shown an association between HAT and a higher risk of adverse events such as seizures and opioid overdoses11 than methadone or buprenorphine/naloxone. While HAT carries a more dangerous safety profile than other forms of OAT, HAT administration typically occurs in supervised clinical settings, which lessens these risks. Thus, while HAT carries an increased absolute risk of adverse events—including opioid overdose—it is still a harm reduction measure as it lessens the risk relative to the unsupervised consumption of street-sourced heroin or fentanyl.

Given the regulatory restrictions in providing HAT, investigators in Vancouver, Canada, considered alternative strategies for treating individuals with TR-OUD. The search for alternative OAT led to hydromorphone, a synthetic opioid used to treat chronic pain. Consequently, researchers at St Paul’s Hospital in Vancouver conducted the Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) trial.

 The SALOME trial was one of the first to establish the efficacy of these harm reduction measures for a population of individuals with TR-OUD. Consequently, the SALOME trial suggests that when diacetylmorphine is unavailable or other treatments are unsuccessful, IH can be a suitable alternative for treating severe TR-OUD.

In January 2019, Vancouver started the first hydromorphone tablet distribution program, based on the promising results of the SALOME trial. A qualitative study evaluated its effects, suggesting that it can decrease illicit drug use, overdose risk, engagement in illegal activities, and address social inequalities surrounding drug use.

, take-home hydromorphone has been permitted, and the effects of this expansion can be promising for the wide-scale implementation of similar programs in rural, suburban, and urban settings.

 However, further study of injectable and oral hydromorphone in TR-OUD patients in diverse settings is warranted.

Supervised consumption facilities (SCFs) are safe and clean indoor facilities where individuals can use pre-obtained drugs under the supervision of trained medical professionals to ensure safe injection or other consumption (eg, oral or smoked) methods. In parallel, SCFs can implement rapid responses in opioid overdoses, such as by providing intranasal or intramuscular naloxone.

 SCFs have emerged in Canadian cities such as Toronto, Ottawa, and Halifax as grassroots initiatives to address unmet needs for special populations with TR-OUD or other substance use disorders. These SCF initiatives can also assist in different ways by providing counselling and psychosocial supports, referrals to social services, and access to medical and psychiatric treatment where necessary.

SCFs were first developed in response to the HIV epidemic in Vancouver when Insite—North America’s first SCF—proved to be a tremendous asset in combating the 

 One of the additional benefits of SCFs is that they can provide a multifaceted opportunity to address comorbidities, such as psychiatric illness, HIV/AIDS, and other infectious diseases. As individuals with TR-OUD frequently experience co-occurring medical and psychiatric disorders, SCFs have created critical opportunities to engage with a population that is difficult to reach otherwise. Various studies have demonstrated their myriad benefits, such as decreasing overdose deaths, crime, and infectious disease transmission while remaining cost-effective.

A recent study estimated the cost and impact of establishing SCFs in New York City. It showed that an SCF can prevent 19 to 37 opioid overdose fatalities per year in New York City and between $831,700 and $2.9 million in costs would be saved by the healthcare system.

 However, this remains a controversial topic in the United States, and advocacy for drug policy changes must continue.

The overdose crisis has negatively affected all Canadian provinces and territories, with British Columbia, Ontario, and Alberta recording the highest number of opioid-related overdose deaths in 2019.

 The United States has also seen a widespread increase in the number of opioid-related deaths since the 2000s, with the Northeast, Mid-Atlantic, and Mid-Western states being most impacted.

 (> 90%) appear to be accidental. The high prevalence of fentanyl as an adulterant in the illegal supplies of heroin and other injectable drugs (eg, cocaine and crystal methamphetamine) are the major factors accounting for the growing number of overdose-related deaths.

The most commonly used opioid agonist therapies (OAT) in Canada and the United States are methadone and buprenorphine/naloxone. However, their availabilities vary across regions and by insurance coverage.

The rising number of opioid-related fatalities is a call to action to implement sustainable measures to prevent overdose occurrences beyond acute naloxone administration. Canada has implemented multiple harm reduction measures since the beginning of its opioid crisis, which have reduced overdose mortality. For example, the current safe supply programs focus on prescribing pharmaceutical-grade opioids, such as injectable hydromorphone and diacetylmorphine, to individuals at high risk of 

. These can be powerful aids to reducing the harm of fentanyl-related opioids from the illicit drug market, and as a result, prevent overdose events and decrease overdose mortality.

 Canadian and international SCF studies have shown effectiveness in reducing overdose fatalities and decreasing needle sharing, unsafe injection practices, and involvement in criminal activities.

 As Canada and the United States take action to combat the current opioid crisis, they can learn from the collective expertise and strategies implemented on either side of the border to search for comprehensive, collaborative, and evidence-based approaches to the opioid crisis.

is a Fellow in Addiction Psychiatry in the Cumming School of Medicine at the University of Calgary, Calgary, Canada.

is a Staff Psychiatrist in the Addictions Division at the Centre for Addiction and Mental Health (CAMH) and Lecturer in Psychiatry, Temerty Faculty of Medicine, University of Toronto.

is an Advanced Practice Clinical Leader at CAMH, and a PhD candidate in the Bloomberg School of Nursing at the University of Toronto.

is Professor of Anthropology and Psychiatry, and Research Chair in the Social Medicine Theme, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

is Professor of Psychiatry in the Temerty Faculty of Medicine at the University of Toronto, and Clinician-Scientist in the Addictions Division at CAMH in Toronto, Canada. He also serves as Deputy Editor of the journal Neuropsychopharmacology (NPP).

The constructive and critical comments of Dr Eric C. Strain of John Hopkins University on the manuscript are gratefully acknowledged.

1. Ivsins A, Boyd J, Beletsky L, McNeil R. Tackling the overdose crisis: The role of safe supply. 

2. Government of Canada. Opioid- and Stimulant-related Harms in Canada (Maps). Accessed March 24, 2021. 

3. National Institute on Drug Abuse. Overdose death rates. January 29, 2021. 

4. Government of Canada. (March 24, 2021). Opioid- and Stimulant-related Harms in Canada (Key Findings). 

5. Centers for Disease Control and Prevention. Overdose deaths accelerating during COVID-19 – expanded prevention efforts needed. December 18, 2020. 

6. Schuckit MA. Treatment of opioid-use disorders. 

7. Priest KC, Gorfinkel L, Klimas J, et al. Comparing Canadian and the United States opioid agonist therapy policies. 

8. Hansen HB, Siegel CE, Case BG, et al. Variation in buprenorphine and methadone treatment by racial, ethnic, and income characteristics of residential social areas in New York City. 

9. Young S, Fairbairn N. Expanding supervised injection facilities across Canada: lessons from the Vancouver experience. 

10. Drug Policy Alliance. Heroin assisted treatment (HAT). February 2016. 

11. Oviedo-Joekes E, Brissette S, Marsh DC, et al. Diacetylmorphine versus methadone to treat opioid addiction. 

12. Oviedo-Joekes E, Guh D, Brissette S, et al. Hydromorphone compared with diacetylmorphine for long-term opioid dependence: A randomized clinical trial. 

13. Timko C, Schultz NR, Cucciare MA, et al. Retention in medication-assisted treatment for opiate dependence: A systematic review. 

14. Ivsins A, Boyd J, Mayer S, et al. "It’s helped me a lot, just like to stay alive": a qualitative analysis of outcomes of a novel hydromorphone tablet distribution program in Vancouver, Canada. 

15. Behrends CN, Paone D, Nolan ML, et al. Estimated impact of supervised injection facilities on overdose fatalities and healthcare costs in New York City. 

How can understanding the opioid crisis in Canada inform strategies in the United States?

Nazanin Izadi, HBSc

Articles

Harnessing Harm-Reduction Methods to Combat the Opioid Crisis

Lessons from Novel Harm Reduction Methods