Importance: While some have argued that cannabis legalization has helped to reduce opioid-related morbidity and mortality in the US, evidence has been mixed. Moreover, existing studies did not account for biases that could arise when policy effects vary over time or across states or when multiple policies are assessed at the same time, as in the case of recreational and medical cannabis legalization.

Question: What is the association of recreational and medical cannabis legalization with opioid prescriptions and fatal overdoses in the US?

Findings: In this cohort study using state-level data and a generalized difference-in-differences method that accounted for possible contamination from multiple laws, there was no discernible association found between cannabis laws and opioid prescriptions nor fatal opioid overdose, although the results suggested a potential reduction in synthetic opioid deaths associated with recreational cannabis laws. These results were robust to excluding state economic indicators, accounting for additional opioid laws and using alternative ways to code treatment dates.

Meaning: The study results suggest that recreational and medical cannabis legalization were not associated with significant increases or decreases in opioid prescriptions and fatal overdose with the exception of a possible reduction in synthetic opioid deaths that was associated with recreational cannabis law implementation.