title: Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  CBD (5mg/kg; i.p.) was administered over 4weeks to mice that had undergone BDL.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Human Nutrition and Metabolism, Braun's School of Public Health, Hadassah-Hebrew University Medical Faculty, 91120 Jerusalem, Israel.
authors: Iddo
authors: I
authors: Magen
authors: Yosefa
authors: Y
authors: Avraham
authors: Zvi
authors: Z
authors: Ackerman
authors: Lia
authors: L
authors: Vorobiev
authors: Raphael
authors: R
authors: Mechoulam
authors: Elliot M
authors: EM
authors: Berry
mesh_terms: D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001652:Bile Ducts / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002185:Cannabidiol / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020233:Gait Disorders, Neurologic / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000150:complications* / Q000209:etiology; D008026:Ligation / Q000009:adverse effects; D008107:Liver Diseases / Q000150:complications* / Q000209:etiology; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D016896:Treatment Outcome; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D047888:Receptors, Tumor Necrosis Factor, Type I; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; D002185:Cannabidiol; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2