The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors

Psychopharmacology (Berl). 2011 Feb;213(2-3):465-73. doi: 10.1007/s00213-010-2036-z. Epub 2010 Oct 14.


Rationale: Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic-like effects in rodents and humans after systemic administration. Previous results from our group showed that CBD injection into the bed nucleus of the stria terminalis (BNST) attenuates conditioned aversive responses. The aim of this study was to further investigate the role of this region on the anxiolytic effects of the CBD. Moreover, considering that CBD can activate 5-HT1A receptors, we also verified a possible involvement of these receptors in those effects.

Methods: Male Wistar rats received injections of CBD (15, 30, or 60 nmol) into the BNST and were exposed to the elevated plus-maze (EPM) or to the Vogel conflict test (VCT), two widely used animal models of anxiety.

Results: CBD increased open arms exploration in the EPM as well as the number of punished licks in the VCT, suggesting an anxiolytic-like effect. The drug did not change the number of entries into the enclosed arms of the EPM nor interfered with water consumption or nociceptive threshold, discarding potential confounding factors in the two tests. Moreover, pretreatment with the 5-HT1A receptor antagonist WAY100635 (0.37 nmol) blocked the effects of CBD in both models.

Conclusions: These results give further support to the proposal that BNST is involved in the anxiolytic-like effects of CBD observed after systemic administration, probably by facilitating local 5-HT1A receptor-mediated neurotransmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Anxiety / drug therapy*
  • Cannabidiol / administration & dosage
  • Cannabidiol / isolation & purification
  • Cannabidiol / pharmacology*
  • Cannabis / chemistry*
  • Conflict, Psychological
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Male
  • Maze Learning / drug effects
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A / drug effects*
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Septal Nuclei / drug effects
  • Septal Nuclei / metabolism
  • Serotonin Antagonists / pharmacology


  • Anti-Anxiety Agents
  • Piperazines
  • Pyridines
  • Serotonin Antagonists
  • Receptor, Serotonin, 5-HT1A
  • Cannabidiol
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide