Introduction: Tramadol abuse is increasing among male and female teenagers with a history of substance abuse and anxiety. Many adolescent addicts take tramadol as substitute for other narcotics. Tramadol uptake is associated with many side effects. Thyme has been presumed to have a neuroprotective effect against brain damage. Aim of the work:To assess the harmful effects of tramadol on the pre and postnatal development of the rat cerebellar granule cells and to evaluate the possible ameliorative effect of thyme if being administered with tramadol simultaneously.Material & Methods: Three sets of forty-eight mature female albino rats were randomly organized into three equal groups; control (G1), tramadol treated (G2) and tramadol+thyme treated (G3). After pregnancy, the pregnant rats of each group were categorized into a group designed to be sacrificed at the gestational ages 13 th , 16th and 19 th for the prenatal study. In the other pregnant rat group, their offspring were further subdivided according to their ages into 3 subgroups (newborn, 10 th and 20 th postnatal day) for postnatal evaluation. G1 was not given any treatment. Tramadol HCL (40 mg/Kg/day) dissolved in tab water was given orally to G2. Tramadol (40 mg/Kg/day) and thyme extract (500 mg/kg/day) were given orally to G3. A light, electron microscopic examination and morphometric analysis were performed in the study. Results: By light and electron microscopic examination, there were degenerative and apoptotic changes in the cerebellar cortex of G2. G3 showed improvement in histological changes. Morphometric results showed a decrease in the cerebellar cortex thickness between the G1 and G2 which was significant and an increase in the cerebellar cortex thickness G3 when compared with that of G2. Conclusion:The study assigns that tramadol administration induces adverse effects on the prenatal and postnatal development of the rat cerebellar cortex. It also highlights an improving role of thyme in tramadol-induced cerebellar cortex injury of the pre and postnatal development.

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Background: Tramadol is a painkiller that works by acting on the central nervous system. Even though tramadol is regarded to have minimal misuse and dependence potential, it is increasingly being used in pregnant women in many countries throughout the world, notably in the Middle East, Africa, and West Asia, to relieve pain from rheumatoid arthritis, cancer, and other diseases. Aim of the work: To assess the harmful effects of tramadol on the postnatal development of the cerebellar Purkinje cells of rats and to evaluate the possible ameliorative effect of thyme if being administered with tramadol simultaneously. Material & Methods: Three sets of Forty-eight mature female albino rats were randomly organized into three equal groups; Group 1 (control), group 2 (tramadol treated) and group 3 ( tramadol+thyme treated). The rats' offspring of the fore mentioned three groups were further subdivided according to their ages into 3 subgroups (newborn, 10 th, and 20 th postnatal day). Group I have not received any treatment. Tramadol HCL (40 mg/Kg/day) dissolved in tab water was given orally to group B. Tramadol (40 mg/Kg/day) and thyme extract (500 mg/kg/day) were given orally to group C. From the first day of pregnancy until weaning, female rats were administered tramadol and thyme. For each of the three groups, the Purkinje cell layer of the cerebellar cortex of the rats' offspring (newborn, 10 th, and 20 th postnatal day) was then examined for histological, ultrastructural, immunohistochemical changes and morphometric analysis. Results: Histological, ultrastructural and immunohistochemistry studies showed that in GII there were neuronal frittering and apoptotic changes in the Purkinje neurons. In GIII, an improvement in histological, ultrastructural and immunohistochemical changes was observed. The morphometric results revealed that there was a significant statistical difference at 10 th and 20 th postnatal age whereas no recorded significant statistical difference at newborn age among the experimental groups. Conclusion: Tramadol use during pregnancy and breastfeeding had a neurotoxic impact on the development of Purkinje cells of the cerebellar cortex of rats. Thyme extract can ameliorate the tramadol's harmful effects; hence it may be useful in the therapy of tramadol neuronal damage if tramadol is required.