The use of illicit drugs has become a worldwide health problem. Substances with the potential to be abused may have direct or indirect effects on physiologic mechanisms that lead to organ system dysfunction and diseases. The present study aims to investigate the structural and reabsorption integrity of the nephron among Egyptian addicts of tramadol alone and coabused with cannabis. Sixty-five males were included in the study, they were classified into control group (G₁=19), tramadol addicts group (G₂=18), and tramadol co-abused with Cannabis addicts group (G₃=28). Parameters investigated for structural integrity were urinary levels of leucineaminopeptidase and N-acetyl-β-D-glucosaminidase, and urinary parameters for reabso-rption integrity were levels of copper and zinc as well as calcium, also urinary creatinine was measured. In addition, urinary levels of tramadol and tetrahydrocannabinol were estimated. Among the two addicted groups, all measured parameters were not significantly different in comparison with the control group except for urinary calcium excretion which was found to be significantly increased among the two addicted groups. Both tramadol addiction alone or co-abused with cannabis causes increased urinary excretion of calcium, indicating reabsorption dysfunction of calcium without affecting structural integrity along the nephron.