| Summary: | Abstract Background There is a need to identify biomarkers which could indicate the occurrence of brain injury in drug abuse. Objectives We aimed to investigate ubiquitin-C-terminal hydrolase-1 (UCH-L1), a neuronal cell body injury marker, the glial protein S-100 beta (S100β), and the glial fibrillary acidic protein (GFAP) as putative markers for neuronal injury due to cannabis, tramadol, or their combined use. Materials and methods Rats were treated with cannabis and/or tramadol subcutaneously daily for 6 weeks and UCH-L1, S100β, and GFAP were immunoassayed in the brain and serum. Results The results are as follows: (i) either cannabis or tramadol increased UCH-L1 and GFAP in the brain, (ii) serum UCH-L1 and GFAP increased by the highest dose of cannabis or tramadol, (iii) there was no additive effect for cannabis and tramadol on UCH-L1 or GFAP level in the brain or serum, (iv) S100β decreased in the brain by 5–20 mg/kg of cannabis and in the serum following 20 mg/kg of cannabis, and (v) S100β levels increased in the brain after 20 mg/kg of tramadol but decreased the brain and serum after both cannabis and tramadol. Cytoplasmic vacuolations, apoptotic cells, and gliosis were observed in the brain tissue of cannabis and/or tramadol-treated rats. Conclusions These results suggest that changes in UCH-L1, GFAP, or S100β are likely to reflect neurotoxicity and serum levels could be used to detect neuronal damage in chronic users.
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