Novel adulterants in unregulated opioids and their associations with adverse events

In recent years, Canada's unregulated drug supply has become permeated by novel adulterants (e.g., fentanyl analogues, benzodiazepines, xylazine). While fentanyl has been shown to be associated with overdose mortality and other non-fatal health outcomes, adverse events (AE) associated with these adulterants remain poorly described. This study seeks to identify whether common adulterants identified through drug checking services are associated with increased prevalence of specific adverse events reportedly experienced by people who use drugs.

Drug checking samples were analyzed using Fourier-transform infrared spectroscopy and immunoassay strips at harm reduction sites in British Columbia. Self-reported AE (e.g., non-fatal overdose, prolonged sedation, seizures) were recorded from individuals who checked opioids post-consumption. Adjusted prevalence ratios (aPR) and 95% confidence intervals (95% CI) of AE among common adulterants were calculated using generalized linear models with a Poisson distribution, controlled for presence of other adulterants, expected drug, geographic location, and month.

Between February 2022 and May 2024, 80,415 samples were analyzed at community sites. Among eligible samples, 36.1% were expected opioids, 42.2% of which were checked post-consumption. AE were noted among 10.7% of post-consumption opioid drug checks. After adjustment, the presence of benzodiazepines in opioid samples was associated with increased prevalence of any AE (aPR 1.97; 95% CI 1.70-2.27), as was the presence of xylazine (aPR 1.50; 95% CI 1.09-2.07). Considering specific AE, benzodiazepines were associated with increased prevalence of overdose (aPR 2.05; 95% CI 1.68-2.51) and prolonged sedation (aPR 3.35; 95% CI 2.54-4.43).

Non-fatal AE associated with unregulated opioids have been largely undescribed. Our findings report specific AE associated with different adulterants in the unregulated opioid supply. With this information, tailored public health interventions and services focused on these adulterants can be developed.