Background: The co-use of opioids and stimulants is associated with elevated health risks. This study examined patterns of injection drug use and cocaine use frequency among people who use opioids.

Methods: Cross-sectional data were collected from community-recruited adults who use opioids in Baltimore, Maryland, between December 7, 2022 and January 26, 2025. Participants were categorized into four groups based on injection status and cocaine use frequency. Multinomial logistic regression examined factors associated with group membership, calculating relative risk ratios (RRR) and adjusted relative risk ratios (aRRR) with 95 % confidence intervals.

Results: Of 777 participants (60.7 % male, 71.6 % Black, median age 52), 29.2 % reported past-month injection drug use. Daily/almost daily use was reported for heroin/fentanyl (79.5 %), crack cocaine (43.2 %), and powder cocaine (9.3 %). Four distinct drug use patterns emerged: not inject/lower frequency cocaine use (42.0 %), inject/lower frequency cocaine use (9.3 %), not inject/higher frequency cocaine use (28.8 %), and inject/higher frequency cocaine use (19.9 %). Factors significantly associated with injecting and higher frequency cocaine use group membership included: overdose history (aRRR=2.58, 95 % CI=1.52–4.38), withdrawal behavior with high overdose risk (aRRR=1.29, 95 % CI=1.14–1.46), and using in multiple locations (aRRR=1.09, 95 % CI=1.02–1.18).

Conclusions: Nearly one-fifth of people who use opioids reported both injection drug use and high-frequency cocaine use, and greater frequency of cocaine use was associated with higher overdose risk. Targeted interventions addressing polysubstance use patterns, social networks, and environmental factors are urgently needed to reduce harm among this high-risk population.