In Reply Bleyer and Barnes are right to call attention to the need for further investigation on the association of cannabis legalization to opioid deaths—a critical area that must be researched. In their response to our recently published article,1 and an article by Wen and Hockenberry,2 Bleyer and Barnes compared an aggregated opioid death rate for 19 states and the District of Columbia that are identified as having some form of legalized cannabis with the rate in 24 states that have no such laws. In contrast to our results, and the existing body of literature, the authors found that by December 2016, the opioid death rate had increased by 52% in states with any form of legalized cannabis compared with states with no cannabis law.