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Background: Substance misuse among teenagers has increased dramatically in recent years, and drug abuse amongst younger people has also steadily increased, with more youngsters beginning to use substances at a young age.The Aim of the work: The purpose of this study is to provide insight into the prevalence of teenage substance misuse and its trends in the toxicology and psychiatry departments of Al-Azhar University Hospital [New Damietta] between December 2020 and December 2022.Methods: In order to determine the prevalence of substance usage, a total of 140 abused adolescents were involved, along with 30 healthy participants serving as a control group. Within sixty minutes after arriving at the hospital's emergency department, blood specimens were taken in tubes containing sodium fluoride [NaF]. After that, it was maintained at 4–8 °C for standard lab analyses. High-performance liquid chromatography [HPLC] was used as an additional confirmation, and radioimmunoassay strips were used as an initial test. Every health record was gathered for both the cases and the control subjects. This was conducted beside the clinical assessment, which focused on the Glasgow Coma Scale [GCS] and neurological evaluation.Results: Tramadol was the most often abused medication among adolescents, closely followed by cannabis. Tramadol and cannabis were the most often abused medications in the control group, then combined use and anti-psychotic medications, antihistamines, benzodiazepines and cough suppressants, amphetamine, and antidepressants. When comparing the study group to the controls, there was a notable variation in the way that tramadol, cannabis, cough suppressants, and pharmacological combinations were administered.Conclusion: The most commonly misused drug among teenagers is tramadol, which is followed by cannabis, combined use and anti-psychotic medications, benzodiazepines, antihistamines, amphetamine, cough suppressants, and anti-depressants, respectively.