OBJECTIVE: Cannabis sativa L has remained the most widely used recreational and abused drug worldwide. This study determined adipose tissue histological changes and the anxiety-like behavior in elevated plusmaze tests in rats treated with C. sativa. METHODS: C. sativa L. was provided from Islamic Azad University Herbarium. To reach cannabis powder, a rotary evaporator was used. Forty-fi ve male Wistar rats were randomly divided into three equal groups of experimental receiving 2 mg/kg of cannabis extract dissolved in 70 % ethanol in 0.6 mL volume subcutaneously daily for three weeks, the sham group subcutaneously injected with equal volume of 70 % ethanol and the control receiving just distilled water, identically. To assess the anxiety level, elevated plus maze was used. Histopathological changes in adipose tissue was evaluated after 7, 14, and 21 days post-intervention. RESULTS: After cannabis administration, infl ammation, degeneration and necrosis in adipose tissue occured. Regarding the anxiety level for the percentage of time spent in open arm (OAT), the percentage of time spent in closed arm (CAT), the percentage of time spent in central parts, and head dipping over the side of the maze) after one week, no signifi cant difference was noticed between the groups; but 2 and 3 weeks of cannabis use, the anxiety level signifi cantly increased. CONCLUSION: Histological fi ndings denoted to infl ammation, degeneration and necrosis in adipose tissue after cannabis use. Behavioral assessment of anxiety level revealed that one week after cannabis, no changes were seen in anxiety, but 2 and 3 weeks after cannabis use, the anxiety level increased signifi cantly (Fig. 5, Ref. 38).