Background & Aim: This study was designed to evaluate the toxic effects of Cannabis sativa local gin formulation (CSLGF) and tramadol in adult female Wistar rats.Experimental: Cannabis sativa local gin formulation (CSLGF) was prepared and was subjected to acute toxicity tests together with tramadol. In the main study, 25 rats were assigned into 5 groups (n = 5) in which the group 1 received no treatment, groups 2 and 3 received 25 and 50 mg/kg of tramadol, respectively while groups 4 and 5 received 25 and 50 mg/kg of CSLGF, respectively, for 21 days before the rats were sacrificed.Results: Acute toxicity results indicated narrow margins of safety for CSLGF and tramadol with LD50 values of 123.0 and 133.0 mg/kg body weight, respectively. The rats treated with CSLGF lost weight significantly while that administered tramadol had lower weight gains when compared with the control (P<0.05). The red blood cell counts, packed cell volume and haemoglobin concentrations were significantly lowered by CSLGF (P<0.05). However, a significant increase in the number of platelets and white blood cells were observed in groups treated with both CSLGF and tramadol. Results of biochemical changes showed a significant increase in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, urea and creatinine with a concurrent decrease in total protein, albumin and globulin values following treatment with both agents (P<0.05), but serum electrolytes concentrations were not significantly altered (P>0.05). Treatment with CSLGF and tramadol also significantly lowered glutathione, superoxide dismutase and catalase activities but increased malondialdehyde concentrations when compared with control.Recommended applications/industries: The findings show that although the toxic effects of CSLGF and tramadol in rats are similar, CSLGF appears to have higher toxicity potentials. Extending the current control on tramadol to CSLGF (monkey tail) is urgently needed in Nigeria to protect human lives. Manuscript profile