A cannabidiol (CBD) oral lipid-based nanoemulsion induces anxiolytic- and panicolytic-like effects and increases delta-FosB immunoreactivity in serotonergic cells of the dorsal raphe lateral wings

Abstract

Background: Cannabidiol (CBD) is a phytocannabinoid of Cannabis sativa which seems to hold benefit for anxiety-related disorders. The present study aimed to evaluate the possible anxiolytic- and panicolytic-like effects of an oral lipid-based CBD nanoemulsion in animal models. Methods: Male Wistar rats were orally treated for 21 consecutive days with CBD (2.5 and 5 mg/kg, 1 mL/kg PO) or vehicle (1 mL/kg) and on the 21st day tested in the avoidance and escape tasks of the elevated T-maze (ETM) for measurements of an anxiety and a panic-related response, respectively. After ETM measurements, animals were also evaluated for anxiety-related behavior in the light/dark transition model and had their motor activity assessed in an open field. Additionally, we evaluated delta-FosB immunoreactivity (Fos-ir) in serotonergic cells of the dorsal raphe (DR). Results:CBD showed an anxiolytic (decreased ETM avoidance latencies) and a panicolytic-like effect (increased ETM escape latencies) at the dose of 2.5 mg/kg. This same dose tended to decrease the time spent in the dark compartment, while at the same time increasing time spent in the light compartment of the light/dark transition model. Treatment with 5 mg/kg was without effect. No changes in locomotor activity were found. CBD also significantly decreased Fos-ir in different columns of the periaqueductal gray and in the dorsal region (DRD) and lateral wings (lwDR) of the DR. Tryptophan hydroxylase immunoreactivity was increased in the lwDR, DRD and ventral regions of the DR. Double immunostaining, however, was only increased in the lwDR, the main DR subnucleus associated to the modulation of panic-related responses, after treatment with CBD 2.5 mg. Conclusions: These results suggest the efficacy of an oral lipid-based CBD nanoemulsion for the treatment of anxiety-related disorders and contribute to a better understanding of the behavioral and neurobiological effects of CBD in anxiety and panic.