Fabad Journal of Pharmaceutical Sciences, vol.50, no.1, pp.39-50, 2025 (Scopus)
The use of synthetic cannabinoids (SCs) increases dramatically among youth from different cultures. UR- 144 is one of these SCs that was reported in 2012 for its first abuse. Case reports indicate symptoms of neuronal toxicity following UR-144 treatment, while several laboratory studies have demonstrated that UR-144 induces apoptosis and oxidative stress in various cell lines. However, none of those studies evaluate the effects of UR-144 in neuronal cells. This study aims to explore the molecular impacts of UR-144 on human neuroblastoma (SH-SY5Y) cells. MTT and neutral red uptake (NRU) assays were performed to evaluate the cytotoxicity. Oxidative stress was examined using the total antioxidant capacity test (TAC) and the changes in reactive oxygen species (ROS) and malondialdehyde (MDA) levels. The Comet assay was used to assess DNA damage. Results indicate that UR-144 did not cause cell death after 24 hours of treatment by MTT test. However, the cell death ratio at 50 µM was 19.34%. UR-144 significantly decreased the levels of ROS and MDA in the cells, but no change in TAC levels was noticed. The comet assay results indicate no genotoxicity of UR-144 in SH-SY5Y cells. While these results indicate no significant toxicity of UR-144 SCs, further studies should be planned to illuminate the mechanism underlying the neuronal symptoms in UR-144 cases and approve or disapprove these results.