title: Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects.
abstract: Cannabidiol (CBD) is a major Cannabis sativa constituent, which does not cause the typical marijuana psychoactivity. However, it has been shown to be active in a numerous pharmacological assays, including mice tests for anxiety, obsessive-compulsive disorder, depression and schizophrenia. In human trials the doses of CBD needed to achieve effects in anxiety and schizophrenia are high. We report now the synthesis of 3 fluorinated CBD derivatives, one of which, 4'-F-CBD (HUF-101) (1), is considerably more potent than CBD in behavioral assays in mice predictive of anxiolytic, antidepressant, antipsychotic and anti-compulsive activity. Similar to CBD, the anti-compulsive effects of HUF-101 depend on cannabinoid receptors.
authors.affiliation: Institute for Drug Research, Medical Faculty, Hebrew University, Jerusalem, Israel.
authors.forename: Aviva
authors.initials: A
authors.lastname: Breuer
authors.affiliation: Institute for Drug Research, Medical Faculty, Hebrew University, Jerusalem, Israel.
authors.forename: Christeene G
authors.initials: CG
authors.lastname: Haj
authors.affiliation: Departments of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Manoela V
authors.initials: MV
authors.lastname: Fogaça
authors.affiliation: Departments of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Felipe V
authors.initials: FV
authors.lastname: Gomes
authors.affiliation: Departments of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Nicole Rodrigues
authors.initials: NR
authors.lastname: Silva
authors.affiliation: Neuroscience and Behavior, Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: João Francisco
authors.initials: JF
authors.lastname: Pedrazzi
authors.affiliation: Department of Morphology, Physiology and Pathology, School of Odontology of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Del Bel
authors.affiliation: Neuroscience and Behavior, Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Jaime C
authors.initials: JC
authors.lastname: Hallak
authors.affiliation: Neuroscience and Behavior, Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: José A
authors.initials: JA
authors.lastname: Crippa
authors.affiliation: Neuroscience and Behavior, Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Antonio W
authors.initials: AW
authors.lastname: Zuardi
authors.affiliation: Institute for Drug Research, Medical Faculty, Hebrew University, Jerusalem, Israel.
authors.forename: Raphael
authors.identifier: http://orcid.org/0000-0002-6122-5698
authors.initials: R
authors.lastname: Mechoulam
authors.affiliation: Departments of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Guimarães
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy; D001008:Anxiety Disorders / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects*; D002185:Cannabidiol / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy; D003866:Depressive Disorder / Q000188:drug therapy; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D002185:Cannabidiol