ca56fb88-1c21-48f3-8f78-2c277c53a3b920250527080642223wseas:wseasmdt@crossref.orgMDT DepositMOLECULAR SCIENCES AND APPLICATIONS2732-99922944-913810.37394/232023https://wseas.com/journals/msa/index.php42320254232025510.37394/232023.2025.5https://wseas.com/journals/msa/2025.phpAmany A.SleemDepartment of Pharmacology Medical Research and Clinical Studies Institute, National Research Centre Tahrir Street, Dokki, Cairo EGYPTEman R.YounessDepartment of Medical Biochemistry Medical Research and Clinical Studies Institute, National Research Centre Tahrir Street, Dokki, Cairo EGYPTEnayat A.OmaraDepartment of Pathology Medical Research and Clinical Studies Institute, National Research Centre Tahrir Street, Dokki, Cairo EGYPTOmar M. E.Abdel-SalamDepartment of Toxicology and Narcotics Medical Research and Clinical Studies Institute, National Research Centre Tahrir Street, Dokki, Cairo EGYPTThe protein brain derived neurotrophic factor (BDNF) is a member of the neurotrophins family involved in neuronal differentiation and survival and in regulation of synaptic plasticity in brain. Neuron specific enolase (NSE) is found in the cytoplasm of brain neurons and is detected in serum after neuronal cell death. This study examined the effect of repeated administration of cannabis, tramadol or their combination on serum levels of BDNF and NSE. Rats received different doses of Cannabis sativa extract, tramadol or both on daily basis via the subcutaneous route for four weeks. The levels of BDNF and NSE in serum were determined by ELISA. Compared to the vehicle control: (i) serum BDNF showed significant increase in rats given cannabis at 5 mg/kg but decreased after treatment with 10 or 20 mg/kg cannabis; (ii) BDNF decreased after high dose of tramadol and by the combined administration of both cannabis and tramadol; (iii) serum NSE level was significantly raised in cannabis-treated animals. It also increased by tramadol and after combined treatment with cannabis and tramadol. The histopathological examination of the substantia nigra in animals administered cannabis or tramadol demonstrated the occurrence of degenerated neuronal cells. This was characterized by the presence of shrunken cells with pyknotic nuclei and perineuronal vacuolations, which were observed in a dose-dependent manner. Furthermore, the simultaneous administration of tramadol with cannabis resulted in a notable rise in the number of degenerated cells, which displayed reduced size, shrunken pyknotic nuclei, and perineuronal vacuolations. These results confirm the occurrence of neuronal cell damage in brain after repeated cannabis and/or tramadol administration. It is suggested that BDNF or NSE may be a useful biochemical marker for the detection of neuronal cell injury in abusers of cannabis and/or tramadol.5272025527202519273https://wseas.com/journals/msa/2025/a06msa-003(2025).pdf10.37394/232023.2025.5.3https://wseas.com/journals/msa/2025/a06msa-003(2025).pdf10.18356/9789210019545c005UNODC, World Drug Report (United Nations publication, 2024), [Online]. Vienna, Austria. https://www.unodc.org/unodc/en/data-andanalysis/world-drug-report-2024. (Accessed Date: Feb 20, 2025). 10.1016/b978-0-12-800756-3.00013-2Abdel-Salam OME, Galal AF, Elshebiney SA, Gaafar AEDM. International aspects of cannabis use and misuse: Egypt. In: Preedy V (Ed.), Handbook of Cannabis and Related Pathologies: Biology, Pharmacology, Diagnosis and Treatment, 1st Edition. 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