Specific provisions of legal cannabis legislation and regulation could influence cannabis initiation, frequency and quantity of use, and progression to cannabis use disorder. This brief essay highlights scientifically based principles and risk factors that underlie substance use and addiction that can be leveraged to inform policies that might mitigate the development and consequences of cannabis use disorder. Specifically, pharmacologic, access/availability, and environmental factors are discussed in relation to their influence on substance use disorders to illustrate how regulatory provisions can differentially affect these factors and risk for addiction. Relevant knowledge from research and experience with alcohol and tobacco regulation are also considered. Research designed to inform regulatory policy and to evaluate the impact of cannabis legislation on cannabis use and problems is progressing. However, definitive findings will come slowly, and more concerted efforts and resources are needed to expedite this process. In the meantime, policymakers should take advantage of the large body of scientific literature on substance use to foster empirically-guided, common sense approaches to cannabis policy that focus on prevention of addiction.