Cannabidiol prevents cerebral infarction via a serotonergic 5-hydroxytryptamine1A receptor-dependent mechanism

Stroke. 2005 May;36(5):1077-82. doi: 10.1161/01.STR.0000163083.59201.34. Epub 2005 Apr 21.


Background and purpose: Cannabidiol has been reported to be a neuroprotectant, but the neuroprotective mechanism of cannabidiol remains unclear. We studied the neuroprotective mechanism of cannabidiol in 4-hour middle cerebral artery (MCA) occlusion mice.

Methods: Male MCA occluded mice were treated with cannabidiol, abnormal cannabidiol, anandamide, methanandamide, cannabidiol plus capsazepine, and cannabidiol plus WAY100135 before and 3 hours after MCA occlusion. The infarct size was determined after 24 hours (2,3,5-triphenyltetrazolium chloride staining). Cerebral blood flow (CBF) was measured at, before and 1, 2, 3, and 4 hours after MCA occlusion.

Results: Cannabidiol significantly reduced the infarct volume induced by MCA occlusion in a bell-shaped curve. Similarly, abnormal cannabidiol but not anandamide or methanandamide reduced the infarct volume. Moreover, the neuroprotective effect of cannabidiol was inhibited by WAY100135, a serotonin 5-hydroxytriptamine1A (5-HT1A) receptor antagonist but not capsazepine a vanilloid receptor antagonist. Cannabidiol increased CBF to the cortex, and the CBF was partly inhibited by WAY100135 in mice subjected to MCA occlusion.

Conclusions: Cannabidiol and abnormal cannabidiol reduced the infarct volume. Furthermore, the neuroprotective effect of cannabidiol was inhibited by WAY100135 but not capsazepine, and the CBF increased by cannabidiol was partially reversed by WAY100135. These results suggested that the neuroprotective effect of cannabidiol may be related to the increase in CBF through the serotonergic 5-HT1A receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acids / therapeutic use
  • Cannabidiol / antagonists & inhibitors
  • Cannabidiol / therapeutic use*
  • Cerebral Infarction / blood
  • Cerebral Infarction / physiopathology
  • Cerebral Infarction / prevention & control*
  • Cerebrovascular Circulation / drug effects
  • Endocannabinoids
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / physiopathology
  • Male
  • Mice
  • Neuroprotective Agents / antagonists & inhibitors
  • Neuroprotective Agents / therapeutic use*
  • Piperazines / pharmacology
  • Polyunsaturated Alkamides
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Resorcinols / therapeutic use
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists / pharmacology


  • 4-(3-3,4-p-menthadien-(1,8)-yl)olivetol
  • Arachidonic Acids
  • Endocannabinoids
  • Neuroprotective Agents
  • Piperazines
  • Polyunsaturated Alkamides
  • Resorcinols
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists
  • Receptor, Serotonin, 5-HT1A
  • WAY 100135
  • methanandamide
  • Cannabidiol
  • anandamide