Is UR-144 Synthetic Cannabinoid Toxic to The Neuronal Cells: An In Vitro Evaluation

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 show neuronal toxicity symptoms after UR-144 exposure and a few laboratory studies show cell death, apoptosis, and oxidative stress in different cell lines. However, none of those studies evaluate the toxicity in neuronal cells. In this study, it was hypothesized that UR-144 induces toxicity in human neuroblastoma (SH-SY5Y) cells. To test that, MTT and neutral red uptake (NRU) assays were performed to evaluate the cytotoxicity. Oxidative stress was evaluated using the total antioxidant capacity test (TAC), which measures the changes in reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Comet assay was used to evaluate the DNA damage. Results indicate that UR-144 did not cause cell death after 24 hours of exposure. A significant decrease in ROS and MDA levels with no change in TAC levels was noticed. 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 of these results.