Background: In North America, since the outset of the COVID-19 pandemic, there has been an unprecedented rise in novel psychoactive substances in the illicit opioid supply, including fentanyl-related analogues, benzodiazepines, and xylazine. In Canada, drug market toxicity and volatility are compounding the existing overdose crisis associated with the rise of illicit fentanyl as the dominant street opioid beginning a decade ago. We sought to characterize how a rapidly shifting drug supply is impacting people who use drugs in Vancouver, Canada with a specific focus on overdose experience.

Methods: Between July and September 2024, we conducted semi-structured qualitative interviews with 31 people who use street drugs in Vancouver’s Downtown Eastside neighbourhood, a global epicentre of drug supply toxicity. Data were thematically analyzed using deductive and inductive approaches, with themes interpreted using the intersectional risk environment framework.

Results: Among participants, the adulteration of street opioids with illicit benzodiazepines and, to a lesser extent, tranquilizers, led to common experiences of memory loss, short-term blackouts, and prolonged loss of consciousness. Short and long-term loss of consciousness compounded participants’ vulnerability to everyday violence, with women and men associating these experiences with sexual assault and extreme physical violence, respectively. However, experiences of losing consciousness due to adulterants (benzodiazepines, tranquilizers) in street opioids were rarely characterized as ‘overdose,’ which was reserved for events requiring medical intervention (e.g., naloxone, emergency medical personnel). Some participants developed a preference for “benzo-dope” over time. Subsequent benzodiazepine dependence deterred individuals from engaging with supportive treatment interventions.

Conclusion: Interventions and policies that directly address the increasing toxicity and volatility of the illicit drug market (e.g., a safe and regulated drug supply) are urgently required. Efforts to address emerging benzodiazepine use and dependence are also urgently needed, as are gender-responsive and targeted strategies to reduce the risk of violence occurring because of benzodiazepine/tranquilizer “blackouts.”