Multi-drug combinations in national apparent opioid and stimulant toxicity deaths

On this page

• Key findings
• Definitions
• Background
• Methods
• Results
• Discussion
• Limitations
• Conclusion
• Acknowledgements
• Technical notes
• References

Key findings

• Data from the national opioid- and stimulant-related harms surveillance system were used to identify and classify the substances and substance class combinations in Canada that occurred the most. Reports were included if more than 1 substance or substance class from the opioid, stimulant or psychoactive substance class was involved in substance-related toxicity deaths in Canada from 2018 to 2022. A substantial overlap in apparent opioid toxicity deaths (AOTDs) and apparent stimulant toxicity deaths (ASTDs) was observed, as most AOTDs involve a stimulant and most ASTDs involve an opioid.
• The most common substance and substance class combinations identified in AOTDs were fentanyl with methamphetamine, cocaine or other psychoactive substances. In ASTDs, common combinations included cocaine with fentanyl and methamphetamine with fentanyl. However, these varied by year, sex and province or territory.
• Combinations involving non-fentanyl opioids were more common among females compared to other substances. Fentanyl involvement was more common among males across all years for AOTDs. Combinations involving methamphetamine were more common among females compared to other substances for ASTDs. Cocaine involvement was more common among males across all years.
• Among AOTDs in Western and Central provinces, fentanyl with other psychoactive substances and fentanyl with methamphetamine were predominately identified in 2022. In Atlantic Canada, the prevailing combination was non-fentanyl opioids with other psychoactive substances.
• Among ASTDs in Western and Central provinces, combinations such as methamphetamine with fentanyl and cocaine with fentanyl were predominantly identified in 2022. In Atlantic Canada, the most common combinations were cocaine with other psychoactive substances and cocaine with non-fentanyl opioids.

Definitions

Apparent opioid toxicity death (AOTD)

Death caused by intoxication or toxicity (poisoning) resulting from substance use, where 1 or more of the substances is an opioid, regardless of how it was obtained (for example, illegally or prescription). Other substances may also be involved.

Apparent stimulant toxicity death (ASTD)

Death caused by intoxication or toxicity (poisoning) resulting from substance use, where 1 or more of the substances is a stimulant, regardless of how it was obtained (for example, illegally or prescription). Other substances may also be involved.

Multi-drug toxicity

The involvement (detection or contribution) of at least 2 substances or substance classes from the opioid, stimulant or other psychoactive substance class for AOTDs and ASTDs.

Other psychoactive substances

A broad category of substances, including alcohol, benzodiazepines, gabapentinoids, ketamine, LSD, PCP, psilocin, W-18 and Z-drugs. This definition may vary across jurisdictions.

Background

The ongoing substance-related overdose crisis continues to have a significant public health impact in Canada. As of December 2023, national surveillance data reported 36,442 apparent opioid toxicity deaths (AOTDs) between January 2016 and December 2022. The number and rate of deaths has increased since the beginning of the COVID-19 pandemic^{Footnote 1}. In 2022, 7,328 AOTDs were reported in Canada, with 8 provinces and territories reporting 2,308 apparent stimulant toxicity deaths (ASTDs)^{Footnote 1}.

Multiple factors have contributed to the escalation of the crisis, such as^{Footnote 2Footnote 3Footnote 4Footnote 5} :

• the emergence and widespread shifts in the drug supply to potent synthetic substances
• drug adulteration, which includes the combination of multiple substances
• the long-lasting impact of the COVID-19 pandemic lockdowns and subsequent economic and mental health impacts

In Canada in 2022, more than half (56%) of accidental AOTDs involved a stimulant, while over three-quarters (78%) of accidental ASTDs also involved an opioid. This reflects the polysubstance nature of the crisis^{Footnote 1}.

In addition to intentional polysubstance use for a preferred experiential effect, an increase in polysubstance use may have been driven by disruptions in illegal drug supply and reduced access to pharmaceuticals due to COVID-19 lockdowns^{Footnote 6Footnote 7Footnote 8}. Unintentional polysubstance use due to contamination and unpredictable compositions of substances in the illegal drug supply may increase the risk of acute toxicity^{Footnote 2}. Polysubstance use, whether intentional or not, may lead to multi-drug toxicity events, including death^{Footnote 9Footnote 10Footnote 11}.

Identifying the combinations of substances that are involved in fatal outcomes is crucial for understanding the impact and developing effective public health actions to address the complex landscape of multi-toxicity deaths. While previous studies have explored substance combinations involved in substance-related toxicity deaths^{Footnote 10Footnote 11}, there is a gap in recent knowledge at the national level in Canada.

Research gap and objective

This work seeks to address this gap by exploring the most frequently occurring combinations of substances and substance classes from 2018 to 2022. In this study, more than 1 substance from the opioid, stimulant and other psychoactive substance class was involved in reported AOTDs and ASTDs in Canada.

Methods

Data source

Data were obtained from the national opioid- and stimulant-related harms surveillance system, as reported by the federal, provincial and territorial Special Advisory Committee on the Epidemic of Opioid Overdoses. The surveillance system relies on death investigation findings from the 13 provincial and territorial chief coroner and chief medical examiner offices. Deaths with completed or ongoing investigations, where death was classified as accident, suicide or undetermined, from January 2018 to December 2022, were included in analysis.

AOTD data from all 13 provinces and territories in Canada for all years and ASTD data for up to 8 provinces and territories, varying by year, for the reporting period were available. As AOTDs and ASTDs are not mutually exclusive, there is an overlap between deaths classified as AOTDs and ASTDS. Therefore, the number of deaths cannot be summed due to duplication of cases.

The substances or substance classes in these data were:

• fentanyl
• fentanyl analogues
• non-fentanyl opioids
• cocaine
• methamphetamine
• other stimulants
• other psychoactive substances (for example, benzodiazepines and alcohol)

The only specific substances identified were fentanyl, cocaine and methamphetamine. Data for fentanyl analogues, non-fentanyl opioids, other stimulants and other psychoactive substances were broad categories that did not specify the individual substances involved in the deaths. Due to variations in death classification methods, the term "involving" was used to describe deaths where substances were detected in the death, whether or not it contributed to the death.

Inclusion and exclusion criteria

All available provincial and territorial surveillance data for AOTDs and ASTDs from January 2018 to December 2022 and submitted to the Public Health Agency of Canada (PHAC) by May 3, 2023, were included in the analysis. AOTDs that occurred before 2018 were excluded due to challenges in distinguishing fentanyl from fentanyl analogues in many jurisdictions. Data on stimulants and other psychoactive substances were not collected before 2018 as well.

Additional data notes on provincial specific data are in the technical notes section.

Statistical analysis

Aggregate surveillance data for AOTDs and ASTDs were used to describe national estimates of multi-drug combinations, where at least 2 different substances or substance classes were involved in deaths. The analysis was limited to 2 substances or substance classes. However, more than 2 substances or substance classes may have been involved in deaths.

Percentages of deaths were reported for each substance and substance class combination by year. Descriptive analyses were also stratified by sex (male or female) and by province and territory. Due to varying data availability across jurisdictions and years, the denominators used to calculate percentages differ across substance and substance class combinations. For example, where provinces and territories were unable to report information on substances or substance classes involved in deaths, deaths reported by these jurisdictions were excluded from national-level denominators.

In the analysis, 15 possible combinations were considered. However, the focus was on identifying the top combinations based on their most frequent occurrences across various categories, including nationally, by province and territory and by sex.

Weighted frequencies were used to identify the 5 highest substance and substance class combinations by jurisdiction. From these, a value (ranging from 2 to 10) was assigned based on their ranking. The highest frequency (rank #1) for each region was assigned 10 points and the lowest (rank #5) was assigned 2 points. Points were then summed for each combination to determine the top 5 combinations overall. All percentages associated with small counts (5 or less) were suppressed.

Results

Overall

The following deaths were reported from 2018 to 2022:

• 29,687 deaths from AOTDs in Canada
• 13,238 deaths from ASTDs deaths by 8 provinces and territories
  • not all of them provided data every year

There appears to be an increase in the number of AOTDs and ASTDs in Canada. Fentanyl was involved in a substantial proportion of AOTDs, followed by cocaine, methamphetamine and other psychoactive substances (Table 1A). Among ASTDs, methamphetamine and fentanyl were involved in a majority of deaths (Table 1B).

There was also an overlap in the involvement of both opioid and stimulants. Approximately 30% of AOTDs involved cocaine or methamphetamine and 70% of ASTDs involved fentanyl.

Table 1A: Percentage of AOTDs by substance or substance class involved in deaths, Canada, 2018-2022

Substance or substance class involved with AOTDs	Year
	2018	2019	2020	2021	2022Footnote 1
Fentanyl	4,207 (70%)	1,967 (60%)	4,693 (80%)	5,285 (81%)	3,347 (64%)
Fentanyl analogues	368 (9%)	672 (21%)	764 (13%)	1,163 (18%)	825 (16%)
Non-fentanyl opioids	1.939 (46%)	1,456 (44%)	1,820 (31%)	1,559 (24%)	1,215 (23%)
Cocaine	1,414 (28%)	1,026 (30%)	2,089 (37%)	2,089 (41%)	1,328 (33%)
Methamphetamine	1,086 (37%)	896 (34%)	2,022 (38%)	2,496 (34%)	1,556 (28%)
Other stimulants	74 (2%)	47 (2%)	258 (5%)	252 (4%)	80 (2%)
Other psychoactive substances	1,843 (44%)	1,428 (43%)	2,574 (44%)	2,924 (48%)	2,011 (43%)
TotalFootnote 2	4,207	3,291	5,862	6,551	5,224
Footnote 1 Deaths observed in 2022 are preliminary and subject to change as investigations are closed. Return to footnote 1 referrer Footnote 2 Due to varying data availability across provinces and territories, denominators used for percentage calculations differ per substance involved (refer to the methods section). Return to footnote 2 referrer

Table 1B: Percentage of ASTDs by substance or substance class involved in deaths, Canada (based on 5 to 8 provinces and territories), 2018-2022

Substance or substance class involved with ASTDs	Year
	2018	2019	2020	2021	2022Footnote 1
Fentanyl	1,462 (70%)	923 (53%)	2,410 (75%)	2,565 (75%)	1,596 (69%)
Fentanyl analogues	122 (6%)	363 (21%)	441 (14%)	546 (16%)	343 (15%)
Non-fentanyl opioids	654 (31%)	415 (24%)	619 (19%)	569 (17%)	365 (16%)
Cocaine	1,573 (44%)	1,219 (46%)	2,226 (51%)	2,138 (54%)	1,477 (53%)
Methamphetamine	920 (70%)	798 (65%)	1,632 (66%)	1,848 (63%)	1,213 (64%)
Other stimulants	158 (7%)	132 (7%)	463 (14%)	336 (10%)	115 (5%)
Other psychoactive substances	693 (31%)	537 (29%)	1,044 (31%)	987 (29%)	638 (28%)
TotalFootnote 2	2,256	1,870	3,395	3,408	2,309
Footnote 1 Deaths observed in 2022 are preliminary and subject to change as investigations are closed. Return to footnote 1 referrer Footnote 2 Due to varying data availability across provinces and territories, denominators used for percentage calculations differ per substance involved (refer to the methods section). Return to footnote 2 referrer Note: Data on AOTDs and ASTDs were not mutually exclusive. A high proportion of deaths involving a stimulant also involved an opioid. Adding up those numbers would overestimate the burden of opioids and stimulants. For some provinces and territories, only data on deaths with completed investigations, where relevant toxicology information was available, were reported. Substances collected differ by province and territory. Data on stimulant involvement in AOTDs for Quebec and New Brunswick were not available (refer to the technical notes section for details). Fentanyl, fentanyl analogues and non-fentanyl opioids belong to the opioids class. Cocaine, methamphetamine and other stimulants belong to the stimulants class. Data on individual substances within the "other psychoactive substances" class were not available (refer to Table C). The number of provinces and territories reporting ASTDs was 5 in 2018, 6 in 2019 and 8 in 2020 to 2022.

Most common substance and substance class combinations in AOTDs

The 7 most common substance or substance class combinations in AOTDs for each year (Figure 1) were:

• fentanyl with cocaine (25% to 34%)
• fentanyl with other psychoactive substances (23% to 37%)
• fentanyl with methamphetamine (23% to 39%)
• non-fentanyl opioids with other psychoactive substances (11% to 23%)
• fentanyl with non-fentanyl opioids (8% to 20%)
• fentanyl with fentanyl analogues (5% to 16%)
• fentanyl analogues with other psychoactive substances (4% to 13%)

The combinations of fentanyl with cocaine, fentanyl with other psychoactive substances and fentanyl with methamphetamine became more frequent in the most recent years. The involvement of non-fentanyl opioids was more frequent before the COVID-19 pandemic, but seems to have decreased since 2020, particularly with other psychoactive substances.

Figure 1 - Text description

Long description for the bar chart illustrating the percentage of total AOTDs by the top substance and substance class combinations involved in deaths in Canada from 2018 to 2022.

Figure 1: Percentage of total AOTDs by the top substance and substance class combinations involved in deaths, Canada, 2018 to 2022.

Substance and substance class combination	Year
	2018	2019	2020	2021	2022
Fentanyl with cocaine	1,196 (31%)	753 (25%)	1,889 (34%)	1,885 (31%)	1,146 (25%)
Fentanyl with other psychoactive substances	1,091 (26%)	761 (23%)	1,904 (32%)	2,270 (37%)	1,381 (29%)
Fentanyl with methamphetamine	949 (25%)	687 (23%)	1,883 (34%)	2,350 (39%)	1,420 (31%)
Non-fentanyl opioids with other psychoactive substances	905 (22%)	758 (23%)	970 (17%)	722 (12%)	518 (11%)
Fentanyl with non-fentanyl opioids	824 (20%)	479 (15%)	763 (13%)	778 (12%)	443 (8%)
Fentanyl with fentanyl analogues	193 (5%)	262 (8%)	696 (12%)	1,032 (16%)	700 (13%)
Fentanyl analogues with other psychoactive substances	170 (4%)	151 (5%)	386 (7%)	770 (13%)	521 (11%)
Total	4,207	3,291	5,862	6,551	5,224

Note: As the deaths by substance and substance class combination are not mutually exclusive, the percentages may not sum up to 100%. For some provinces and territories, only data on deaths with completed investigations, where relevant toxicology information was available, were reported. As such, the decrease in deaths observed in 2022 is preliminary and subject to change as investigations are closed. Substances collected differ by jurisdiction as well. Data on stimulant involvement in AOTDs for Quebec and New Brunswick were not available (refer to the technical notes section for details). Due to varying data availability across jurisdictions, the denominators used to calculate the percentage of AOTDs differ per substance and substance class combination (refer to the methods section).

Sex distribution

Since 2018, the top 7 substance and substance class combinations in AOTDs have differed between sexes.

Among females (Figure 2A):

• nearly 40% of AOTDs consistently involved non-fentanyl opioids with other psychoactive substances
• 20% to 30% of AOTDs involved other substance combinations across all years

Among males, a high proportion of deaths across all years involved the following substance and substance class combinations (Figure 2B):

• fentanyl with fentanyl analogues (72% to 80%)
• fentanyl analogues with other psychoactive substances (71% to 80%)
• fentanyl with cocaine (74% to 78%)

In both sexes, variations were evident from year to year.

Figure 2A and 2B - Text description

Long description for the bar charts illustrating the percentage of total AOTDs by the top 5 substance and substance class combinations involved in deaths by sex in Canada from 2018 to 2022.

Figures 2A and 2B. Percentage of total AOTDs by top 7 substance and substance class combinations involved in deaths by sex, Canada, 2018 to 2022

Substance and substance class combination	Sex	Year
		2018	2019	2020	2021	2022
Fentanyl with methamphetamine	Female	240 (25%)	189 (28%)	472 (25%)	649 (28%)	407 (29%)
	Male	709 (75%)	498 (72%)	1,411 (75%)	1,699 (72%)	1,009 (71%)
Fentanyl with other psychoactive substances	Female	263 (24%)	203 (27%)	440 (23%)	597 (26%)	369 (27%)
	Male	828 (76%)	558 (73%)	1,464 (77%)	1,672 (74%)	1,011 (73%)
Fentanyl with cocaine	Female	273 (23%)	189 (25%)	417 (22%)	482 (26%)	285 (25%)
	Male	923 (77%)	564 (75%)	1,472 (78%)	1,401 (74%)	856 (75%)
Non-fentanyl opioids with other psychoactive substances	Female	343 (38%)	302 (40%)	380 (39%)	265 (37%)	193 (37%)
	Male	562 (62%)	456 (60%)	590 (61%)	590 (63%)	325 (63%)
Fentanyl with non-fentanyl opioids	Female	211 (26%)	142 (30%)	226 (30%)	219 (28%)	130 (29%)
	Male	613 (74%)	337 (70%)	537 (70%)	558 (72%)	313 (71%)
Fentanyl with fentanyl analogues	Female	38 (20%)	62 (24%)	157 (23%)	289 (28%)	196 (28%)
	Male	155 (80%)	200 (76%)	539 (77%)	743 (72%)	502 (72%)
Fentanyl analogues with other psychoactive substances	Female	38 (22%)	30 (20%)	90 (23%)	204 (26%)	152 (29%)
	Male	132 (78%)	121 (80%)	296 (77%)	566 (74%)	369 (71%)

Note: The deaths by substance and substance class combination are not mutually exclusive, and so the percentages may not sum up to 100%. For some provinces and territories, only data on deaths with completed investigations, where relevant toxicology information was available, were reported. As such, the decrease in deaths observed in 2022 is preliminary and subject to change as investigations are closed. Also, substances collected by provinces and territories vary. Therefore, the number of jurisdictions that contribute to national estimates differs by substance and substance class combination. In particular, data on stimulant involvement in AOTDs for Quebec and New Brunswick were not available (refer to the technical notes section for details). Due to varying data availability across jurisdictions, the denominators used for percentage calculations differ per substance and substance class combination (refer to the methods section). Deaths where sex was reported as "other" or "unknown" were excluded from the analysis.

Regional distribution

The most frequently identified substance and substance class combinations in AOTDs reported in 2022 differed by region. This may reflect differences in substance access, use and composition across jurisdictions.

The most commonly identified combinations in AOTDs in British Columbia and Alberta included fentanyl with other psychoactive substances and fentanyl with methamphetamine. In Ontario, fentanyl with cocaine was the most commonly identified combination. In Saskatchewan, Manitoba and Quebec, fentanyl analogues with other psychoactive substances was commonly reported. In Newfoundland, Nova Scotia and New Brunswick, the most common substance combination was non-fentanyl opioids with other psychoactive substances (Figure 3). In Yukon, the most common substance combinations were fentanyl with other psychoactive substances as well as fentanyl with cocaine.

Figure 3 - Text description

Long description for the bar chart illustrates the percentage of total AOTDs by top 5 substance and substance class combinations involved in deaths and jurisdiction in 2022.

Figure 3: Percentage of AOTDs by top substance and substance class combinations involved in deaths and jurisdiction in 2022

Province or territory	Substance and substance class combination
	Fentanyl with non-fentanyl opioids	Non-fentanyl opioids with other psychoactive substances	Fentanyl analogues with other psychoactive substances	Fentanyl with other psychoactive substances	Fentanyl with cocaine	Fentanyl with methamphetamine	Fentanyl with fentanyl analogues
BC	37 (16%)	28 (12%)	31 (13%)	119 (50%)	75 (32%)	102 (43%)	50 (21%)
AB	82 (5%)	116 (8%)	265 (18%)	636 (42%)	175 (12%)	479 (32%)	258 (17%)
SK	24 (10%)	58 (25%)	114 (49%)	123 (52%)	19 (8%)	119 (51%)	150 (64%)
MB	27 (52%)	58 (58%)	43 (83%)	43 (83%)	28 (54%)	33 (63%)	45 (87%)
ON	225 (9%)	30 (8%)	59 (2%)	427 (17%)	830 (33%)	685 (27%)	177 (7%)
QC	41 (8%)	n/a	n/a	n/a	n/a	n/a	10 (2%)
NB	n/a	26 (57%)	8 (17%)	16 (35%)	n/a	n/a	6 (13%)
NS	Suppr.	42 (68%)	Suppr.	Suppr.	6 (10%)	Suppr.	Suppr.
PE	Suppr.	Suppr.	Suppr.	Suppr.	n/a	n/a	Suppr.
NL	Suppr.	20 (83%)	Suppr.	Suppr.	Suppr.	Suppr.	Suppr.
YT	Suppr.	Suppr.	Suppr.	10 (53%)	9 (47%)	Suppr.	Suppr.
NT	Suppr.	Suppr.	Suppr.	Suppr.	Suppr.	Suppr.	Suppr.
NU	Suppr.	Suppr.	Suppr.	Suppr.	n/a	n/a	Suppr.
Total	443	518	521	1,381	1,146	1,420	700

Note: As the deaths by substance and substance class combination are not mutually exclusive, the percentages may not sum up to 100%. For some provinces and territories, only data on deaths with completed investigations, where relevant toxicology information was available, were reported. As such, the decrease in deaths observed in 2022 is preliminary and subject to change as investigations are closed. Data on stimulant involvement in AOTDs for Quebec and New Brunswick were not available. Data were not presented for Prince Edward Island, Northwest Territories and Nunavut due to small counts. For some jurisdictions, only data on deaths with completed investigations, where relevant toxicology information was available, were reported. Data by substance for British Columbia were based only on illicit opioid toxicity deaths for which investigations are completed (refer to the technical notes section for details). The top substance combinations vary by jurisdiction. They were based on the substance and substance class combinations with the highest weighted frequencies provincially and territorially in 2022 (refer to the methods section).

Suppressed (Suppr.): Data are suppressed in provinces or territories with small case counts (5 or less) in order to comply with confidentiality rules.
Not available (n/a): Data were not available at the time of this publication.

Most common substance and substance class combinations in ASTDs

The 6 most frequent combinations of substances or substance classes in ASTDs from 2018 to 2022 each year (Figure 4) were:

• cocaine with fentanyl (36% to 50%)
• methamphetamine with fentanyl (26% to 44%)
• cocaine with methamphetamine (13% to 19%)
• cocaine with other psychoactive substances (17% to 23%)
• methamphetamine with other psychoactive substances (10% to 16%)
• cocaine with non-fentanyl opioids (10% to 22%)

Figure 4 - Text description

Long description for the bar chart illustrates the percentage of total ASTDs by the top substance and substance class combinations involved in deaths in Canada from 2018 to 2022.

Figure 4: Percentage of total ASTDs by the top substance and substance class combinations involved in deaths, Canada(based on 5 to 8 provinces and territories), 2018 to 2022

Substance and substance class combinations	Year
	2018	2019	2020	2021	2022
Cocaine with fentanyl	1,020 (49%)	614 (36%)	1,586 (50%)	1,566 (46%)	971 (42%)
Methamphetamine with fentanyl	695 (33%)	446 (26%)	1,317 (41%)	1,494 (44%)	941 (41%)
Cocaine with other psychoactive substances	515 (23%)	377 (20%)	696 (21%)	597 (18%)	389 (17%)
Cocaine with non-fentanyl opioids	450 (22%)	265 (15%)	385 (12%)	370 (11%)	232 (10%)
Cocaine with methamphetamine	333 (16%)	226 (13%)	605 (19%)	626 (18%)	405 (18%)
Methamphetamine with other psychoactive substances	200 (10%)	171 (10%)	443 (14%)	537 (16%)	338 (15%)
Total	2,256	1,870	3,395	3,408	2,309

Note: As the deaths by substance and substance class combination are not mutually exclusive, the percentages may not sum up to 100%. For some provinces and territories, only data on deaths with completed investigations, where relevant toxicology information was available, were reported. Deaths reported in 2022 are preliminary and subject to change as investigations are closed. ASTD data were also not available for Alberta, Prince Edward Island, New Brunswick and Nunavut. Data on opioid involvement in ASTDs for Quebec were not available (refer to the technical notes section for details). Due to varying data availability across jurisdictions, denominators used for percentage calculations differ per substance and substance class combination (refer to the methods section).

Sex distribution

Since 2018, the top 6 substance and substance class combinations in ASTDs have differed between sexes (Figures 5A and 5B).

Across most years, methamphetamine was involved in the top substance combinations in ASTDs among females (Figure 5A), including:

• cocaine with methamphetamine (27% to 31%)
• methamphetamine with other psychoactive substances (29% to 33%)
• methamphetamine with fentanyl (25% to 27%)

Across most years, in males, a high proportion of substance combination deaths involved cocaine (Figure 5B), including:

• cocaine with fentanyl (74% to 77%)
• cocaine with other psychoactive substances (69% to 77%)
• cocaine with non-fentanyl opioids (62% to 76%)

Nevertheless, slight year-to-year variations exist.

Figure 5A and 5B - Text description

Long description for the bar charts illustrates the percentage of total ASTDs by the top 5 substance and substance class combinations involved in deaths by sex in Canada from 2018 to 2022.

Figures 5A and 5B. Percentage of total ASTDs by top 6 substance and substance class combinations involved in deaths by sex, Canada (based on 5 to 8 provinces and territories), 2018 to 2022.

Substance and substance class combination	Sex	Year
		2018	2019	2020	2021	2022
Cocaine with fentanyl	Female	233 (23%)	156 (25%)	362 (23%)	413 (26%)	240 (25%)
	Male	787 (77%)	458 (75%)	1,224 (77%)	1,151 (74%)	726 (75%)
Cocaine with non-fentanyl opioids	Female	110 (24%)	100 (38%)	135 (35%)	121 (33%)	62 (27%)
	Male	340 (76%)	165 (62%)	250 (65%)	249 (67%)	170 (73%)
Cocaine with methamphetamine	Female	99 (30%)	69 (31%)	172 (28%)	168 (27%)	116 (29%)
	Male	234 (70%)	157 (69%)	433 (72%)	457 (73%)	286 (71%)
Cocaine with other psychoactive substances	Female	121 (24%)	112 (30%)	187 (27%)	183 (31%)	100 (26%)
	Male	394 (77%)	265 (70%)	509 (73%)	413 (69%)	288 (74%)
Methamphetamine with fentanyl	Female	176 (25%)	118 (26%)	334 (25%)	404 (27%)	252 (27%)
	Male	519 (75%)	328 (74%)	983 (75%)	1,088 (73%)	685 (73%)
Methamphetamine with other psychoactive substances	Female	58 (29%)	56 (33%)	131 (30%)	162 (30%)	98 (29%)
	Male	142 (71%)	115 (67%)	312 (70%)	375 (70%)	240 (71%)

Note: As the deaths by substance and substance class combination are not mutually exclusive, the percentages may not sum up to 100%. For some provinces and territories, only data on deaths with completed investigations, where relevant toxicology information was available, were reported. Deaths reported in 2022 are preliminary and subject to change as investigations are closed. ASTD data were also not available for Alberta, Prince Edward Island, New Brunswick and Nunavut. Data on opioid involvement in ASTDs for Quebec were not available (refer to the technical notes section for details). Due to varying data availability across jurisdictions, denominators used for percentage calculations differ per substance and substance class combination (refer to the methods section). Deaths where sex was reported as "other" or "unknown" were excluded from the analysis.

Regional distribution

Commonly reported substance and substance class combinations in ASTDs differed by region in 2022 (Figure 6):

• British Columbia and Ontario: methamphetamine with fentanyl and cocaine with fentanyl
• Newfoundland and Labrador and Nova Scotia: cocaine with other psychoactive stimulants and cocaine with non-fentanyl opioids
• Yukon: cocaine with fentanyl and cocaine with other psychoactive substances

Figure 6 - Text description

Long description for the bar chart illustrates the percentage of total ASTDs by top substance and substance class combinations involved in deaths and jurisdiction in 2022.

Figure 6. Percentage of total ASTDs by top substance and substance class combinations involved in deaths and jurisdiction in 2022

Province and territory	Substance and substance class combination
	Cocaine with non-fentanyl opioids	Methamphetamine with other psychoactive substances	Methamphetamine with fentanyl	Cocaine with other psychoactive substances	Cocaine with methamphetamine	Cocaine with fentanyl
BC	19 (10%)	52 (28%)	102 (54%)	47 (25%)	27 (14%)	75 (40%)
SK	9 (5%)	93 (51%)	119 (65%)	22 (12%)	14 (8%)	19 (10%)
MB	19 (28%)	34 (68%)	33 (66%)	33 (66%)	22 (44%)	28 (56%)
ON	157 (9%)	157 (9%)	685 (38%)	253 (14%)	335 (18%)	830 (46%)
QC	n/a	n/a	n/a	n/a	n/a	n/a
NS	20 (44%)	Suppr.	Suppr.	18 (40%)	Suppr.	6 (13%)
NL	7 (50%)	Suppr.	Suppr.	9 (64%)	Suppr.	Suppr.
YT	Suppr.	Suppr.	Suppr.	7 (47%)	Suppr.	9 (60%)
NT	Suppr.	Suppr.	Suppr.	Suppr.	Suppr.	Suppr.
Total	232	338	941	389	405	971

Note: As the deaths by substance and substance class combination are not mutually exclusive, the percentages may not sum up to 100%. For some provinces and territories, only data on deaths with completed investigations, where relevant toxicology information was available, were reported. As such, the decrease in deaths observed data in 2022 is preliminary and subject to change as investigations are closed. Data from Quebec were not presented as opioid involvement in ASTDs is not available. ASTD data were not available for Alberta, Prince Edward Island, New Brunswick and Nunavut. Data for the Northwest Territories were not presented due to small counts. Data by substance for British Columbia were based only on stimulant toxicity deaths for which investigations are completed (refer to the technical notes section for details). The top substance and substance class combinations vary by jurisdiction. They were based on the substance and substance class combinations with the highest weighted frequencies provincially and territorially in 2022 (refer to the methods section).

Suppressed (Suppr.): Data are suppressed in provinces or territories with small case counts (5 or less) in order to comply with confidentiality rules.
Not available (n/a): Data were not available at the time of this publication.

Discussion

Characterizing the substance and substance class combinations involved in AOTDs and ASTDs in Canada provides valuable insights into the complex landscape of substance toxicity deaths. There is a large overlap of stimulants and opioids in acute toxicity deaths. The most frequently reported combinations were as follows:

• fentanyl with cocaine, methamphetamine or other psychoactive substances in AOTDs
• cocaine with fentanyl and methamphetamine with fentanyl in ASTDs

Combinations of opioids and stimulants have been increasingly commonly reported in substance-related toxicity deaths in recent years^{Footnote 10Footnote 12Footnote 13Footnote 14Footnote 15Footnote 16Footnote 17Footnote 18}.

The increase in polysubstance use may be due to several reasons, such as achieving desired effects and changes in access to a drug of choice. Uncertainties in the composition of substances in the illegal drug supply could also be leading to higher and unknown or unintentional polysubstance use^{Footnote 2Footnote 13Footnote 19}. Changes in the substance and substance class combinations involved in toxicity deaths may also be related to the impacts of the COVID-19 pandemic on the drug supply. In this case, studies have shown that substances of choice were influenced by factors such as scarcity and rising costs^{Footnote 6Footnote 7Footnote 8}.

In our analysis, sex-based differences were evident in AOTDs and ASTDs:

• high non-fentanyl opioids involvement in AOTDs and high methamphetamine involvement in ASTDs among females
• high fentanyl involvement in AOTDs and high cocaine involvement in ASTDs among males

Despite some differences in the sex distribution each year, the most frequent substance and substance class combinations were consistent among males and females since 2018. As this is similar to previous research^{Footnote 10}, it is crucial to identify the factors that may be contributing to the excess toxicity deaths among males. For instance, differences in patterns of substance use by sex may occur (for example, using alone among males or using prescription opioids among females)^{Footnote 19Footnote 20}. Recognizing sex-specific patterns can inform targeted public health interventions.

Examining regional differences in the composition of substance and substance class combinations reveals how geographic factors can influence trends in AOTDs and ASTDs. In 2022, most provinces and territories reported high instances of fentanyl with other psychoactive substances involved in AOTDs. Western and Central provinces also reported a higher proportion of fentanyl with methamphetamine.

More pronounced regional differences were observed in the top substance and substance class combinations for ASTDs. In 2022, Western and Central provinces reported a high proportion of ASTDs involving methamphetamine with fentanyl or other psychoactive substances, as well as cocaine. However, toxicity deaths in Atlantic Canada and the territories often reported involvement of combinations of cocaine with other psychoactive stimulants and cocaine with non-fentanyl opioids.

These findings underscore the regional variation of substance and substance class combinations involved in AOTDs and ASTDs and the importance of ongoing data and surveillance of geographic variations to target interventions and policies. Finally, this descriptive analysis highlights the need for continued surveillance and research into the polysubstance aspect of the overdose crisis in Canada.

Future research should aim to investigate a wider array of substance combinations and demographics. Research should also focus on stratification by age and multi-drug variations involved in deaths.

Limitations

This analysis only includes AOTDs and ASTDs. Information on additional substances that may be involved in AOTDs and ASTDs were not available.

As well, data from the provinces and territories differ in the type and availability of data reported each year and must be interpreted with caution. This includes differences in the definition and composition of substances and substance classes collected (for example, opioids, stimulants, other psychoactive substances). This makes it challenging to summarize and discern temporal trends for certain substance and substance class combinations.

Other limitations include the following:

• data were not available on the amount or potency of the substance or the manner of consumption
• some provinces and territories do not report on specific substances until investigations are completed, which can take up to 24 months
• the surveillance data used for this analysis are subject to change as investigations are completed and totals may appear different from other national surveillance data reports^{Footnote 1}
• as fentanyl currently dominates the illegal drug supply^{Footnote 20}, its prevalence in the multi-drug combinations may obscure combinations of other substances or substance classes involved in deaths

Conclusion

The complex and evolving polysubstance nature of AOTDs and ASTDs highlights the need for multi-pronged prevention and intervention strategies to manage and reduce harms due to the epidemic of opioid overdoses.

Continuing national surveillance to monitor the substance and substance class combinations involved in deaths is vital to informing harm reduction policies and programs.

Acknowledgements

We recognize that the data used in this report may represent stories of pain, grief and trauma. This report cannot adequately reflect the burden borne by Canadians. We acknowledge all those impacted by substance use and those who work to save lives and reduce substance related harms on individuals and communities.

We also express our gratitude to our partners and collaborators who provided the data essential for the national mortality surveillance system on apparent opioid and stimulant toxicity deaths. This includes persons with lived and living experience, the provincial and territorial offices of chief coroners and chief medical examiners, as well as provincial and territorial public health and health care partners. Additionally, we extend our thanks to all reviewers for their valuable contributions to the report and constructive feedback.

Technical notes

Availability of data varies by province and territory and year as outlined in Table A and Table B. Due to these variations, comparisons must be made with caution as direct comparisons may not always be appropriate or reliable.

Table A: Reporting periods and availability of opioid and stimulant data by province or territory, Canada, 2018-2022

		BC	AB	SK	MB	ON	QC	NB	NS	PE	NL	YT	NT	NU
Available data on apparent toxicity deaths involving opioids as of May 3, 2023
2018	January to December	✓ (C)	✓	✓ (C)	✓	✓	✓ (C)	✓	✓	✓ (C)	✓ (C)	✓ (C)	✓	✓
2019	January to December	✓	✓	✓ (C)	✓	✓	✓ (C)	✓	✓	✓ (C)	✓ (C)	✓ (C)	✓	✓
2020	January to December	✓	✓	✓ (C)	✓	✓	✓ (C)	✓	✓	✓ (C)	✓ (C)	✓ (C)	✓	✓
2021	January to December	✓	✓	✓ (C)	✓	✓	✓	✓	✓	✓ (C)	✓ (C)	✓ (C)	✓	✓
2022	January to December	✓	✓	✓ (C)	✓ (INC)	✓	✓	✓	✓	✓ (C)	✓ (C)	✓ (C)	✓	✓
Available data on apparent toxicity deaths involving stimulants as of May 3, 2023
2018	January to December	✓ (C)	n/a	✓ (C)	n/a	✓	✓ (C)	n/a	✓	n/a	n/a	n/a	n/a	n/a
2019	January to December	✓ (C)	n/a	✓ (C)	✓	✓	✓ (C)	n/a	✓	n/a	n/a	n/a	n/a	n/a
2020	January to December	✓ (C)	n/a	✓ (C)	✓	✓	✓ (C)	n/a	✓	n/a	✓ (C)	n/a	✓	n/a
2021	January to December	✓ (C)	n/a	✓ (C)	✓	✓	✓ (C)	n/a	✓	n/a	✓ (C)	✓ (C)	✓	n/a
2022	January to December	✓ (C)	n/a	✓ (C)	✓ (INC)	✓	✓ (C)	n/a	✓	n/a	✓ (C)	✓ (C)	✓	n/a
✓: These data have been reported by the province or territory and were reflected in this update, unless otherwise specified. (C): Data included deaths with completed investigations only. (INC): Data were not available for the entire period. n/a: Data were not available at the time of this publication.

Table B: Substance data notes by jurisdiction, Canada, 2018-2022

Province or territory	Technical notes
BC	AOTD and ASTD data from 2018 to 2022 include deaths with completed investigations only where illicit opioids or stimulants contributed to the death, respectively.
AB	Data on ASTDs were not available for any year. Data on stimulant involvement in AOTDs were available. Only data on deaths with completed investigations, where specific substances causing death were listed on the death certificate, were included for the accidental apparent opioid toxicity deaths involving other non-fentanyl substances. These included non-fentanyl opioids and other psychoactive substances, such as non-opioid substances.
SK	n/a
MB	In 2018, fentanyl and fentanyl analogues were grouped together. Data on ASTDs or stimulant involvement in AOTDs were not available for 2018 or 2022 (April to December).
ON	n/a
QC	From 2018 to 2020, ICD-10 codes were used to code substances contributing to the deaths. Due to the nature of this coding, both opioids and stimulants could not be selected as the cause of death (for example, stimulant involvement in AOTDs or opioid involvement in ASTDs was not available). For 2021 and 2022, AOTD data include deaths related to all drug or opioid intoxications, such as opioids and stimulants. Methamphetamine was included in the "other stimulants" substance category and was not reported as its own category. ASTD data were not available for 2021 and 2022. Only limited data on substances were available for 2021 and 2022.
NB	Until 2021, fentanyl and fentanyl analogues were grouped together. ASTD data and stimulant involvement in AOTDs were not available for any year.
NS	n/a
PE	Until 2019, fentanyl and fentanyl analogues were grouped together. Data on ASTDs were not available for any year. However, data on stimulant involvement in AOTDs were available.
NL	Until 2019, fentanyl and fentanyl analogues were grouped together. Data on ASTDs or stimulant involvement in AOTDs were not available for 2018 and 2019.
YT	Until 2019, fentanyl and fentanyl analogues were grouped together. Data on ASTDs or stimulant involvement in AOTDs were not available from 2018 to 2020.
NT	Until 2019, fentanyl and fentanyl analogues were grouped together. Data on ASTDs or stimulant involvement in AOTDs were not available for 2018 and 2019.
NU	No AOTDs were reported in Nunavut prior to 2022. Data on ASTDs or stimulant involvement in AOTDs were not available for any year.

Table C: Types of opioids and stimulants collected and reported

Substance and substance class	Includes, for example:
Fentanyl and fentanyl analogues	3-methylfentanyl acetylfentanyl acrylfentanyl butyrylfentanyl carfentanil crotonyl fentanyl cyclopropyl fentanyl	despropionyl-fentanyl fentanyl fluoroisobutyrlfentanyl (FIBF) furanylfentanyl methoxyacetylfentanyl norfentanyl
Non-fentanyl opioids	2-methyl AP-237 AH-7921 AP-237 brorphine buprenorphine metabolites codeine desomorphine dihydrocodeine etodesnitazene heroin hydrocodone hydromorphone isopropyl-U-47700 isotonitazene	loperamide meperidine methadone metonitazene mitragynine monoacetylmorphine morphine MT-45 normeperidine oxycodone tapentadol tramadol U-47700 U-49900 U-50488
Stimulants	amphetamine atomoxetine catha cocaine dexamfetamine ethylphenidate lisdexamfetamine MDA MDMA	mephedrone methamphetamine methylphenidate modafinil pemoline phentermine pseudoephedrine TFMPP
Other psychoactive substancesNote de bas de page 1	alcohol benzodiazepines gabapentinoids ketamine LSD	PCP psilocin W-18 Z-drugs
Footnote 1 This substance class is up to the discretion of each jurisdiction and includes any substances that can be considered "psychoactive" As such, it is not an exhaustive list of substances that may be involved in a death. Return to footnote 1 referrer

References