Insights Into Mixing Fentanyl and Benzodiazepines From Canadian Drug Seizures

Abstract

This cohort study uses data from the Drug Analysis Service of Health Canada to describe changes in the presence of benzodiazepines mixed with fentanyl in drug seizures in Canada from 2018 to 2021.

In 2020, there were approximately 60 000 overdose deaths involving synthetic opioids in the US.¹ Illegally produced fentanyl entered the heroin supply, but there are increasing reports of mixtures containing stimulants or nonopioids.² Coingestion of opioids, especially highly potent fentanyls, with benzodiazepines increases risk of death.³

Data lags, limited coordination across US agencies, and the elimination or reduction of the Arrestee Drug Abuse Monitoring program and the Drug Abuse Warning Network impede an understanding of transitioning illicit drug markets. More fundamentally, there are no publicly available incident-level drug seizure data to offer such insights. Comparable US drug seizure data from the National Forensic Laboratory Information System report annual counts from the previous year without describing polydrug mixtures. Better and more current data from Canada can offer some understanding, given its similar experience with illegally manufactured synthetic opioids.

Methods

Canada’s Drug Analysis Service, a part of Health Canada, partners with law enforcement agencies across the country, analyzing some 120 000 drug samples each year.⁴ Data are reported publicly every quarter, with partners receiving monthly analytical reports of event-level drug seizures. Each observation includes measures of different substances detected, the city (if reported) and province of occurrence, the substances’ formulation (eg, powder or tablet, if reported), and the date received. This study examined observations from 2018 through the first quarter of 2021. The significance threshold was set at P < .01 per 1-tailed test. Analysis was completed via R version 4.1 (R Foundation for Statistical Computing).

Results

The total sample of drug seizures involving synthetic opioids was 38 751. The Figure, A shows a rise beginning in 2019 through the first quarter of 2021 in the numbers of benzodiazepine–synthetic opioid seizures by province, particularly in Ontario (mostly in and around Toronto) and British Columbia (mostly in and around Vancouver). Benzodiazepine seizures absent synthetic opioids were stable (not shown). However, approximately 874 synthetic opioid seizures (predominately fentanyl) in Ontario (38%), about one-third in Alberta (n = 226 [31%]), and one-fifth in British Columbia (n = 261 [21%]) also contained benzodiazepines by the first quarter of 2021. This was significantly (P = .003) increased from 1% across provinces in data from 2 years prior (in the first quarter of 2019; Alberta, 5 drug seizures [1%]; British Columbia, 10 drug seizures [1%]; Ontario, 4 drug seizures [<1%]; rest of Canada, 2 drug seizures [1%]). The Table reports counts and shares.

Figure. Seizures of Synthetic Opioid That Contain Benzodiazepines in Canada.

Source: Drug Analysis Service of Health Canada. Other formulations are not shown because of low counts. Q indicates quarter.

Table. Counts and Shares of Synthetic Opioid Exhibits Where Benzodiazepines (BZD) Are Present, by Province and Quarter^a.

Quarter	Alberta		British Columbia		Ontario		Rest of Canada
	BZD present, No. (%)	BZD not present, No.	BZD present, No. (%)	BZD not present, No.	BZD present, No. (%)	BZD not present, No.	BZD present, No. (%)	BZD not present, No.
2018
1	0	98	0	252	0	443	0	27
2	1 (0)	335	1 (0)	1096	0	767	0	70
3	0	259	0	902	0	676	1 (1)	102
4	3 (1)	384	0	968	0	907	3 (3)	91
2019
1	5 (1)	622	10 (1)	1130	4 (0)	1684	2 (1)	149
2	0	441	13 (1)	1144	60 (5)	1119	3 (2)	148
3	0	463	24 (2)	980	63 (5)	1203	8 (7)	111
4	9 (2)	366	23 (3)	894	143 (15)	926	10 (8)	127
2020
1	12 (4)	309	60 (8)	734	205 (17)	1231	9 (11)	82
2	28 (8)	363	61 (5)	1254	146 (10)	1422	13 (8)	153
3	72 (9)	758	163 (9)	1747	264 (10)	2623	31 (14)	219
4	67 (10)	669	178 (13)	1375	561 (29)	1964	70 (18)	389
2021
1b	226 (31)	723	261 (21)	1217	874 (38)	2294	84 (25)	341

^a Data are from the Drug Analysis Service of Health Canada. Shares in parentheses are rounded to the nearest whole number.

^b The increases in shares of synthetic opioid observations that contain BZDs across provinces were significant per a 1-way t test between the first quarter of 2019 and the first quarter of 2021.

The Figure, B shows that virtually all benzodiazepine–synthetic opioid observations found in powder form nationally contained unapproved benzodiazepines (3489 [99%]); few were in tablet form (n = 15). Etizolam, a novel benzodiazepine not approved for use in Canada or the US, was most commonly reported (3082 seizures [87%]). In contrast, tablets largely consisted of diverted controlled benzodiazepines, but there was also a growing share of designer benzodiazepines found in tablets (from 25% to 80%, in terms of BZD counts).⁵

Discussion

There is a recent and alarming trend toward more harmful supply of drugs sold in illegal markets in Canada. Consumers in Ontario, Alberta, and British Columbia buying powder may be at greater risk for exposure to fentanyl mixed with novel benzodiazepines. In the case of novel benzodiazepines, dealers handling powders may be inclined to mix fentanyl with novel benzodiazepines that are marketed online. Designer benzodiazepines in tablets were likely to be illegally manufactured.

Co-consumption of both drugs poses intense challenges to overdose management and elevates the risk of death. Coroner data from British Columbia exemplify this trend; overdose deaths containing benzodiazepines and fentanyl jumped from 15% in mid-2020 to 60% by mid-2021.⁶ Shares of seizures in the province containing both drugs rose by a similar factor of 4, from 5.5% in April 2020 to 23.2% in March 2021.

The main limitation of this analysis is whether or not findings from Canada reflect the true nature of drug market evolutions in the US. Nevertheless, the continued lags in overdose and drug seizure data in the US have serious consequences for public health and safety. Informal early-warning networks mention a similar increase in fentanyl-benzodiazepine overdoses, but without near real–time incident-level drug seizure data, it is impossible to know. There is a need to improve monitoring and surveillance of drug consumption in the US as markets continue to trend toward more harmful drug mixtures.