Fluorinated Cannabidiol Derivatives: Enhancement of Activity in Mice Models Predictive of Anxiolytic, Antidepressant and Antipsychotic Effects

PLoS One. 2016 Jul 14;11(7):e0158779. doi: 10.1371/journal.pone.0158779. eCollection 2016.


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.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Anxiety / drug therapy
  • Anxiety Disorders / drug therapy
  • Behavior, Animal / drug effects*
  • Cannabidiol / pharmacology*
  • Cannabidiol / therapeutic use
  • Depression / drug therapy
  • Depressive Disorder / drug therapy
  • Disease Models, Animal
  • Male
  • Mice
  • Motor Activity / drug effects*
  • Schizophrenia / drug therapy


  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Antipsychotic Agents
  • Cannabidiol

Grant support

The research in Israel was supported by the Kessler Foundation, Boston.