Toxicity and biotransformation studies of the synthetic cannabinoid ADB-INACA using zebrafish (Danio rerio) as an in vivo model

Abstract

New Psychoactive Substances (NSPs) are compounds used due to similar reasons of traditional illicit drugs, recognized for pleasurable and therapeutic effects. Among them, are the synthetic cannabinoid receptor agonists, which act on CB1 and CB2 receptors, comparable to THC but with greater toxicity since they are direct agonists of such receptors, while THC is a partial CB1 agonist. Within this group, ADB-INACA can be highlighted. Its investigation using zebrafish as an in vivo model via fish embyo acute toxicity (FET) test can provide crucial data on its toxic effects, including malformations and embryonic mortality, in addition to clarifying its mechanism of action. Maximum tolerated concentration (MTC) test is essential to define optimal concentrations for larval stage metabolism tests. In addition, the evaluation of the biotransformation products resulting from the exposure of larvae to this drug is important for the elucidation of metabolization pathways, facilitating the detection of the substance and its metabolites in biological matrices through the development of identification methods by liquid chromatography tandem mass spectrometry. Finally, behavioral tests with zebrafish can be performed to elucidate the influence of this substance on the development of important social behaviors, such as sociability. This approaches have the potential to enable a faster and safer diagnosis in cases of poisoning by this type of agent.