Abstract Introduction Existing reviews exploring cannabis effectiveness have numerous limitations including narrow search strategies. We systematically explored cannabis effects on PTSD symptoms, quality of life (QOL), and return to work (RTW). We also investigated harm outcomes such as adverse effects and dropouts due to adverse effects, inefficacy, and all-cause dropout rates. Methods Our search in MEDLINE, EMBASE, PsycInfo, CINAHL, Web of Science, CENTRAL, and PubMed databases, yielded 1 eligible RCT and 10 observational studies (n = 4672). Risk of bias (RoB) was assessed with the Cochrane risk of bias tool and ROBINS-I. Results Evidence from the included studies was mainly based on non-randomized studies...