Prohedonic Effect of Cannabidiol in a Rat Model of Depression

Abstract

Background: Accumulating evidence suggests that cannabidiol (CBD) may be an effective and safe anxiolytic agent and potentially also an antidepressant. Aim: The objective of this study was to further examine these properties of CBD using the ‘depressive-like' Wistar-Kyoto (WKY) rat, focusing on the drug's effect on anhedonia-like behaviors. Methods: Forty-eight WKY and 48 control Wistar adult male rats were pretreated orally with CBD (15, 30 and 45 mg/kg) or vehicle. The saccharin preference test (SPT), the elevated plus maze (EPM) test and the novel object exploration (NOE) test were used. Results: CBD showed a prohedonic effect on the WKY rats at 30 mg/kg in the SPT. In the NOE, CBD increased exploration of the novel object and locomotion at 45 mg/kg and increased locomotion at 15 mg/kg, indicating an improvement in the characteristically low motivation of WKY rats to explore. There was no similar effect at any dose in the EPM or in open-field behavior in the habituation to the NOE. Conclusions: These findings extend the limited knowledge on the antidepressant effect of CBD, now shown for the first time in a genetic animal model of depression. These results suggest that CBD may be beneficial for the treatment of clinical depression and other states with prominent anhedonia.

Cannabidiol improves survival and behavioural co‐morbidities of Dravet syndrome in mice

“…Here, vehicle‐treated Scn1a +/− mice showed typical depression‐like behaviour, that is, a reduced preference to sucrose over water when compared to the WT mice with chronic CBD‐treatment normalising sucrose preference. An antidepressant‐like action of CBD has previously been documented in genetic (Shoval et al, ), olfactory bulbectomy (Linge et al, ) and chronic unpredictable stress (Campos et al, ) models of depression, but we are the first to demonstrate such effect of CBD in any epilepsy model. Although previous studies in naïve rodents have proposed that CBD exerts an antidepressant action via modulating the 5‐HT neurotransmission or endocannabinoid signalling (Campos et al, ; Linge et al, ), the underlying pathology of depression in epilepsy is complex and would necessitate a detailed mechanistic study to gain a better understanding on any antidepressant effect of CBD.…”

Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain: An Update on Current Evidence and Cannabis Science

“…There is medical evidence showing that CBD may be effective in treatment of a wide range of disorders including epilepsy (particularly medically‐refractory pediatric epilepsy syndromes), Alzheimer's disease, Parkinson's disease, MS, ‐ , Huntington's disease, ALS, anxiety disorders including PTSD, depression, dystonia, Meige's syndrome, schizophrenia and psychosis, stroke and hypoxic‐ischemic injury, antioxidant, TBI,…”

Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders

“…More recently, the antidepressant-like effect of CBD was detected in the olfactory bulbectomy (Linge et al, 2016) and learned helplessness models (Pereira et al, 2016). CBD was also effective in rat strains that naturally express “depressive-like behaviors,” such as the Wistar-Kyoto (Shoval et al, 2016). Altogether, this data strengthen the possibility that CBD can induce antidepressant effects.…”