Abstract: Opioid overdose mortality has been increasing rapidly in the U.S., with some states experiencing much larger mortality growth than others. Legalizing medical cannabis could reduce opioid-related mortality if potential opioid users substitute towards cannabis as a safer alternative. I show, however, that a substantial reduction in opioid-related mortality associated with the implementation of medical cannabis laws can be explained by selection bias. States that legalized medical cannabis exhibit lower pre-existing mortality trends. Accordingly, the mitigating effect of medical cannabis laws on opioid-related mortality vanishes when I include state-specific time trends in state-year-level difference-in-differences regressions.