Prohedonic effect of cannabidiol in a rat model of depression

Gal Shoval*, Liat Shbiro, Liron Hershkovitz, Noa Hazut, Gil Zalsman, Raphael Mechoulam, Aron Weller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


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.

Original languageEnglish
Pages (from-to)123-129
Number of pages7
Issue number2
StatePublished - 1 Apr 2016


FundersFunder number
National Institute for Psychobiology in Israel159-14-15
Kessler Foundation


    • Anhedonia
    • Anxiety
    • Cannabidiol
    • Depression
    • Wistar-Kyoto rats


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