Abstract
Several neuropharmacological actions of cannabidiol (CBD) due to the modulation of the endocannabinoid system as well as direct serotonergic and gamma-aminobutyric acidergic actions have recently been identified. The current study aimed to reveal the effect of a long-term CBD treatment in the chronic unpredictable mild stress (CUMS) model of depression. Adult male Wistar rats (n = 24) were exposed to various stressors on a daily basis in order to induce anhedonia and anxiety-like behaviors. CBD (10 mg/kg body weight) was administered by daily intraperitoneal injections for 28 days (n = 12). The effects of the treatment were assessed on body weight, sucrose preference, and exploratory and anxiety-related behavior in the open field (OF) and elevated plus maze (EPM) tests. Hair corticosterone was also assayed by liquid chromatography–mass spectrometry. At the end of the experiment, CBD-treated rats showed a higher rate of body weight gain (5.94% vs. 0.67%) and sucrose preference compared to controls. A significant increase in vertical exploration and a trend of increase in distance traveled in the OF test were observed in the CBD-treated group compared to the vehicle-treated group. The EPM test did not reveal any differences between the groups. Hair corticosterone levels increased in the CBD-treated group, while they decreased in controls compared to baseline (+36.01% vs. −45.91%). In conclusion, CBD exerted a prohedonic effect in rats subjected to CUMS, demonstrated by the increased sucrose preference after three weeks of treatment. The reversal of the effect of CUMS on hair corticosterone concentrations might also point toward an anxiolytic or antidepressant-like effect of CBD, but this needs further confirmation.
Highlights
Cannabidiol (CBD), the major non-psychotomimetic component of different Cannabis species, has been the subject of numerous preclinical and clinical studies, since the endocannabinoid system and its role in neuropsychiatric disorders were first recognized [1,2]
Repeated-measures analysis of variance (ANOVA) showed a significant treatment × trial interaction (F(3, 48) = 3.325, p = 0.0273), supporting the effect of the CBD treatment that increased sucrose preference to a maximum of 82.9% ± 2.43% at day 21 compared to baseline (p = 0.0114); in contrast, the chronic unpredictable mild stress (CUMS) group showed an insignificant fluctuation between 70% and 75% during the stressing period (Figure 4)
The endocannabinoid system is known to exert an inhibitory function over the HPA axis, demonstrated by Steiner et al, who observed the elevation of basal and stress-induced CORT secretion in CB1-deficient mice [43]
Summary
Cannabidiol (CBD), the major non-psychotomimetic component of different Cannabis species, has been the subject of numerous preclinical and clinical studies, since the endocannabinoid system and its role in neuropsychiatric disorders were first recognized [1,2]. The anticonvulsant action of CBD in various childhood epilepsy syndromes (e.g., Dravet syndrome, Lennox–Gastaut syndrome) has been demonstrated, and CBD is available as an ‘orphan medicine’ in the European Union and the United States [3,4,5]. It is marketed in combination with ∆9-tetrahydrocannabinol, the product known as Sativex®, for spasticity and pain in multiple sclerosis. CBD potential antipsychotic, neuroprotective [14], and antidepressant [15] effects have been studied lately
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