Crack/cocaine use to manage xylazine exposure in fentanyl in Connecticut: findings from a convergent mixed methods study

BACKGROUND: In the context of the fourth wave of the opioid overdose crisis, defined by fentanyl and stimulant co-use, we aimed to explore if there might be a relationship between exposure to xylazine in the fentanyl supply and patterns of crack/cocaine use. METHODS: This mixed methods study used data from four Connecticut-based sources: (1) the Office of the Chief Medical Examiner for fatal overdoses, 2019-2023, (2) community-based drug checking data, 2023-2024, (3) a structured survey of people who use drugs, 2024, and (4) one-on-one in-depth interviews, 2024. RESULTS: Xylazine was detected in 19.2% of overdose fatalities involving fentanyl or a fentanyl analog (n = 5,849). Those with xylazine detected had a higher proportion of cocaine simultaneously detected, though this was not statistically significant (54.0% vs. 51.1%, p = 0.085). Cocaine detection rose over time in the fatality data, regardless of xylazine detection. There were 1,048 drug samples submitted to harm reduction organizations for drug checking. Using Fourier Transform Infrared Spectroscopy, 573 of the samples submitted tested positive for fentanyl or a fentanyl analog; 45.2% of these also tested positive for xylazine. Of 1048 samples, 276 tested positive for cocaine. Among the survey sample (n = 88), 62.5% of participants self-reported xylazine exposure. Those who reported lifetime xylazine exposure also reported higher past-year crack/cocaine use, though this was not statistically significant (89.1% vs. 81.8%, p = 0.336). Among our interview sample (n = 31), three themes emerged: (1) participants felt there was an inevitability of polysubstance use due to an increasingly volatile drug supply, (2) participants increased their crack/cocaine use in response to perceived exposure to xylazine in their fentanyl supply, and (3) participants' drug patterning changed due to xylazine's presence (e.g., timing, drug sequencing, etc.). Two meta-inferences were identified: (1) overdose fatality data likely underestimate the "true" prevalence of xylazine in the street supply, and (2) people who use drugs are using crack/cocaine in response to xylazine in their local fentanyl supply. CONCLUSIONS: Xylazine exposure has likely contributed to an adaptive and increasing use of crack/cocaine among people who use drugs in Connecticut. It is imperative that practitioners and policymakers are prepared to manage this triad of opioid-stimulant-sedative polysubstance use.