Cannabinoid signaling is known to modulate behavioral and physiological responses associated with stress, and could be manipulated in the management of stress-aggravated neuropsychiatric disorders. However, there is still a limited understanding of how individual components of this signaling system contribute to stress responsivity. Zebrafish are a genetically tractable vertebrate model that would be particularly useful for studying this interface. Accordingly, we utilized genome editing technology to provide a platform for studying how cannabinoid signaling modifies stress responses in zebrafish. Chapter 1 reviews how zebrafish have been leveraged in the field of cannabinoid biology. Chapter 2 describes the deployment of transposon technology to develop the SR4G zebrafish stress response reporter line, which is used to show that cannabinoid signaling impacts the transcriptional activity of glucocorticoid receptors. Chapter 3 details the deployment of nuclease technology to develop lines with mutations in genes encoding components of the endocannabinoid system, which are used to establish roles for these genes in modulating stress-associated behavior. Chapter 4 concludes with a summary of this thesis, and synthesizes content from the preceding chapters in a discussion about potential future research directions.