Exploring Cannabinoid Effects Using Zebrafish (Danio rerio) as an In Vivo Model: A Review of the Literature

Cannabis is increasingly utilized for both recreational and medical purposes, and the discovery of the endocannabinoid system (ECS) has renewed interest in its therapeutic potential. Nonetheless, the safety of cannabis and cannabinoid-containing products requires re-evaluation. In this study, zebrafish were employed as a translational in vivo model to comprehensively evaluate the toxicological profiles and the therapeutic potential of phytocannabinoids and synthetic cannabinoids. Current evidence, particularly from studies on key phytocannabinoids such as Δ⁹-THC, CBD, and CBN, along with newly developed synthetic cannabinoids (such as JWH-018), demonstrates a spectrum of embryotoxic outcomes including developmental abnormalities, neurotoxicity, liver damage, reproductive impairments, and disturbances in metabolic regulation, especially during early life stages. By contrast, evidence for therapeutic benefits, such as alleviation of muscle spasms, pain and nausea, as well as neuroprotective and anti-inflammatory effects, is promising but comparatively less abundant and more heterogeneous in study design and outcome measures. Taken together, this imbalance indicates that toxicological risks are supported by more extensive and consistent data, whereas therapeutic efficacy, though encouraging, still requires more rigorous validation. This dual profile underscores the need for a robust, evidence-based framework for cannabinoid development and clinical application. Further investigations are essential to clarify mechanisms of toxicity and therapeutic action, optimize dosing regimens, define safe therapeutic windows, and evaluate long-term health outcomes.