In the Swim of Cannabis: Developmental Toxicity and Metabolomic Pathway Alterations of Zebrafish Larvae Exposed to THC for the Assessment of Its Potential Environmental and Human Health Impact

As the pharmacological properties and therapeutic applications of Cannabis sativa L. pace with the upsurge of interest of the scientific community in harnessing its constituent phytocannabinoids, illicit use may raise serious health issues. Tetrahydrocannabinol (THC) is one of the most well-known phytoactive constituents of cannabis and continues to garner scientific and public attention not only because of its pharmacological value but also because over-the-counter products of THC and prescription medications are becoming increasingly available from pharmacies, dispensaries, Internet, local retail stores, or by illicit means. Hence, a multidimensional approach was employed to examine the impact of THC on zebrafish larvae. The acute toxicity, expressed as LC(50), was 1.54 mg/L. Adverse effects were observed on the phenotype, such as tail bending, pericardial edema, etc., even at concentrations lower than LC(50), and fundamental functions of larvae (e.g., heart rate and cardiac contractility, and rhythm) were significantly affected. Behavioral changes were noticed, which were reflected in locomotor activity and sensitivity to light/dark changes. Finally, an untargeted metabolomic study was carried out to shed light on the metabolic alterations that occurred, providing substantiating evidence of the observed phenotype alterations. Overall, the potentially detrimental effects of THC on a vertebrate model are depicted.