The evolving legal cannabis landscape in the US continues to present novel regulatory challenges that necessitate the development of a Cannabis Regulatory Science. Two specific issues of concern within Cannabis Regulatory Science are (1) the impact that cannabis use has on the incidence, prevalence, and severity of mental disorders, and (2) how cannabis laws and regulations modify this impact. This paper first provides several conceptual points that are useful for evaluating the relationship between cannabis use and mental disorders. Second, it selectively reviews and comments on data relevant to the relationship between cannabis use and depression, several forms of anxiety, post-traumatic stress disorder, schizophrenia, and bipolar disorder. Next, regulatory and public health parallels between the nascent cannabis industry and the pharmaceutical, tobacco, and alcohol industries are discussed. The focus is on specific types of industry practices that may harm those with or at risk for mental disorders. Recommendations are then offered for legal cannabis regulations that could mitigate this harm. Last, future research goals are discussed for building the field of Cannabis Regulatory Science and addressing the potential negative impact of cannabis on those with mental disorders.