Behavioral Effects of Chronic Administration of Cannabinoid-Enriched Medicinal Cannabis Oils in Mice

In recent years, interest in therapeutic alternatives for anxiety and depression has increased due to the limitations and adverse effects associated with conventional pharmacological treatments. Among these alternatives are medicinal cannabis oils, whose main studied component, cannabidiol (CBD), has shown beneficial effects on anxiety- and depression-related behaviors in animal models and humans. Given that Cannabis sativa produces more than 100 phytocannabinoids, we aimed to evaluate the therapeutic potential of cannabidiolic acid (CBDA), cannabigerol (CBG), and cannabidivarin (CBDV). Male and female C57BL/6 mice (7–9 week old) received daily oral administration of cannabis oils enriched in CBD, CBDA, CBG, CBDV (100 mg/kg for each of the 4 compounds) or vehicle (sesame oil) for 35 days. Anxiety-related behaviors were assessed using the Elevated Plus Maze and Novelty Suppressed Feeding Test; anhedonia-related behaviors using the Urine Sniffing and Splash Tests; and memory abilities using the Novel Object Recognition test. None of the oils tested produced significant differences compared with the control group in all of the behavioral tests performed. We hypothesize that the lack of behavioral responses may be due to a stable affective state and positive welfare in these animals. Therefore, we propose to re-evaluate these assays in a chronic-induced stress model, to determine whether therapeutic effects emerge under an altered affective state.