Urine drug screens (UDSs) beyond the health care and criminal justice systems have increased throughout the past decade. A proper knowledge of medications that cross-react with UDSs are essential for accurate interpretation of the results. This study aims to evaluate one of the cough medications which may interfere with drug abuse testing and to highlight its plausibility as a defense in the court against dependence. Urine samples were collected from 30 patients presented to Mansoura Toxicology Unit with disturbed conscious level. Thorough history taking, routine laboratory investigations and toxicological analysis of urine for drugs of abuse by enzyme multiplied immunoassay (EMIT) and thin layer chromatography (TLC) were done. EMIT assay revealed that opiates, cannabinoids, benzodiazepines and barbiturates were positive in 100%, 76.7%, 36.6% and 20% of samples respectively. Confirmatory analysis demonstrated positive TLC of morphine in 96.7%, codeine in 43.3%, pholcodine and ephedrine in 53.3% of samples. The opiate positive results in persons taking pholcodine cough syrup proved the plausibility of this drug as a defense in the court in cases with legal and clinical forensic issues. However, each case must be considered on its own merits bearing in mind the need for caution when interpreting the analytical data especially when suspecting the use of pholcodine containing cough mixtures. It is advisable to search for pholcodine and ephedrine to exclude the possibility of taking antitussives containing these compounds. Further studies should be performed to assess the urgent need to schedule these medications. Meanwhile, these drugs should not be sold without a prescription and a warning against positive opiate assay must be written in their pamphlet.