Toxicological profile of JWH-018 and JWH-018 N-(3-Hydroxypentyl) metabolite in the HEK 293 T cell line

Sultan, Haider

http://hdl.handle.net/10400.26/19088

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Authors

Sultan, Haider

Advisor(s)

Quintas, Alexandre

Dias, Mário João

Abstract(s)

The rise in use of synthetic cannabinoids as herbal smoking mixtures has been attributed to a number of reasons; primary among them being their “legality” and their promotion as being safer than the natural alternatives. As their emergence has been quite recent, their pharmacological and toxicological profiles are not known completely. One of the earliest synthetic cannabinoid to be detected in these herbal mixtures was JWH-018. In the present study, the cell toxicity of JWH-018 and its N-(3-hydroxypentyl) metabolite was investigated using human cell line HEK-293 T. The cell viability was assessed using the MTT assay after treatment with standard JWH-018 and its N-hydroxymetabolite in a concentration range between 1ng/ml to 5000ng/ml of both respectively. The results show that the highest concentration of 5000ng/ml shows statistically significant decrease in cell viability for both the parent compound and the metabolite when compared to cell controls. In addition, the metabolite also showed a statistically significant decrease in cell viability at a concentration of 2500ng/ml. There were also significant differences observed between the smaller concentrations (1ng/ml and 10ng/ml) when compared to the highest concentration (5000ng/ml) for both the parent compound and metabolite. The cytotoxic effect was seen at levels which are above the expected tissue levels after use of JWH-018 either by ingestion or smoking. The cytotoxicity of both the parent compound and the metabolite highlights the adverse effects these drugs may have with consequent need for further research and regulation.