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J Hepatol. 2009 Sep;51(3):528-34. doi: 10.1016/j.jhep.2009.04.021. Epub 2009 May 27.

Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation.

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Department of Human Nutrition and Metabolism, Braun's School of Public Health, Hadassah-Hebrew University Medical Faculty, 91120 Jerusalem, Israel.



The endocannabinoid system in mice plays a role in models of human cirrhosis and hepatic encephalopathy (HE), induced by a hepatotoxin. We report now the therapeutic effects of cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, on HE caused by bile duct ligation (BDL), a model of chronic liver disease.


CBD (5mg/kg; i.p.) was administered over 4weeks to mice that had undergone BDL.


Cognitive function in the eight arm maze and the T-maze tests, as well as locomotor function in the open field test were impaired by the ligation and were improved by CBD. BDL raised hippocampal expression of the TNF-alpha-receptor 1 gene, which was reduced by CBD. However, BDL reduced expression of the brain-derived neurotrophic factor (BDNF) gene, which was increased by CBD. The effects of CBD on cognition, locomotion and on TNF-alpha receptor 1 expression were blocked by ZM241385, an A(2)A adenosine receptor antagonist. BDL lowers the expression of this receptor.


The effects of BDL apparently result in part from down-regulation of A(2)A adenosine receptor. CBD reverses these effects through activation of this receptor, leading to compensation of the ligation effect.

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