Óleo de Cannabis de amplo espectro alivia sintomas comportamentais tipodepressivo e tipo-ansioso em camundongos expostos a eventos traumáticos

Abstract

Posttraumatic stress disorder (PTSD) is a psychiatric condition that presents a broad range of symptoms and shares phenotypic similarities with anxiety and depression. Refractory PTSD affects 10–30% of patients, underscoring the necessity for alternative pharmacotherapy. The emerging understanding of the involvement of the endocannabinoid system (ECS) in emotional processes has prompted exploration into the therapeutic potential of Cannabis. Therefore, this study aimed to assess the therapeutic effects of broad-spectrum Cannabis oil on anxiety- and depressive-like behaviors induced by combined stressors. Additionally, the study investigated the impact of the oil on central cannabinoid receptor 1 and serum levels of cytokines, chemokines, and growth factors. Mice were randomly assigned to five groups (vehicle, fluoxetine, and Cannabis oil (0.1, 1, 3, and 10 mg/kg, oral dose) and subjected to acute restraint and chronic unpredictable stress. They were then behaviorally evaluated using the elevated plus-maze test (EPMT), forced swimming test (FST), splash test (ST), and open field test (OFT). The tetrad cannabinoid assay assessed the central effects of the oil, while serum biomarker levels were measured using a multiplex bead-based assay. Cannabis oil (0.1 mg/kg, p.o.) significantly decreased anxiety-like behavior in the EPMT under acute restraint stress (p < 0.05) compared to the vehicle. Moreover, Cannabis oil significantly reversed despair and anhedonic-like behaviors in the FST (p < 0.05) and ST (p < 0.05), respectively, in chronically stressed mice compared to the vehicle. Additionally, therapy with Cannabis oil, compared to the vehicle, did not induce cannabinoid-tetrad effects (p < 0.0001); it downregulated granulocyte-macrophage colony-stimulating factor (GM-CSF; p < 0.01) and advanced glycation end-products (RAGE; p < 0.0001), and upregulated vascular endothelial growth factor (VEGF; p < 0.01) serum levels. Collectively, our data suggest the potential of broad-spectrum Cannabis oil to ameliorate symptoms related to anxiety and depression resulting from traumatic events.