Background: Together with coffee and tobacco, Cannabis is the most commonly used psychoactive drug worldwide, and it is the single most popular illegal drug. Recent studies have demonstrated increase in the prevalence of the use of cannabis. A limitation inherent in all urine drug testing is the possibility of sample adulteration or substitution. Aim of study: To detect qualitative and quantitative effects of five adulterants on positive urine samples for tetrahydrocannabinol carboxylic acid (THC-COOH). Material and Method(s): This analytical study was conducted in Clinical Toxicology Laboratory in Sohag University Hospitals. Urine samples positive to cannabis adulterated with vinegar, drano liquid hand soap, visine eye drops and bleach were tested by immunoassay (RIA) then confirmed and quantified by GC-MS. Results: Urine samples adulterated with vinegar, drano liquid hand soap, visine and bleach generated false negative results by immunoassay testing. GC-MS confirmation showed that addition of vinegar, bleach, visine, drano and liquid hand soap decrease THC-COOH significantly with increased concentration. Conclusion: Some adulterants make it easy to produce false negative results on RIA testing for cannabis and GC-MS is important to overcome adulteration methods in urine analysis