Cannabidiol enhances microglial phagocytosis via transient receptor potential (TRP) channel activation

Br J Pharmacol. 2014 May;171(9):2426-39. doi: 10.1111/bph.12615.


Background and purpose: Microglial cells are important mediators of the immune response in the CNS. The phytocannabinoid, cannabidiol (CBD), has been shown to have central anti-inflammatory properties, and the purpose of the present study was to investigate the effects of CBD and other phytocannabinoids on microglial phagocytosis.

Experimental approach: Phagocytosis was assessed by measuring ingestion of fluorescently labelled latex beads by cultured microglial cells. Drug effects were probed using single-cell Ca²⁺ imaging and expression of mediator proteins by immunoblotting and immunocytochemistry.

Key results: CBD (10 μM) enhanced bead phagocytosis to 175 ± 7% control. Other phytocannabinoids, synthetic and endogenous cannabinoids were without effect. The enhancement was dependent upon Ca²⁺ influx and was abolished in the presence of EGTA, the Ca²⁺ channel inhibitor SKF96365, the transient receptor potential (TRP) channel blocker ruthenium red, and the TRPV1 antagonists capsazepine and AMG9810. CBD produced a sustained increase in intracellular Ca²⁺ concentration in BV-2 microglia and this was abolished by ruthenium red. CBD rapidly increased the expression of TRPV2 and TRPV1 proteins and caused a translocation of TRPV2 to the cell membrane. Wortmannin blocked CBD enhancement of BV-2 cell phagocytosis, suggesting that it is mediated by PI3K signalling downstream of the Ca²⁺ influx.

Conclusions and implications: The TRPV-dependent phagocytosis-enhancing effect of CBD suggests that pharmacological modification of TRPV channel activity could be a rational approach to treating neuroinflammatory disorders involving changes in microglial function and that CBD is a potential starting point for future development of novel therapeutics acting on the TRPV receptor family.

Keywords: calcium influx; cannabidiol; cannabinoid; microglia; phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / metabolism*
  • Cannabidiol / pharmacology*
  • Cells, Cultured
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects
  • Microglia / metabolism*
  • Phagocytosis / drug effects
  • Phagocytosis / physiology*
  • TRPV Cation Channels / metabolism*


  • Calcium Channels
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Trpv2 protein, mouse
  • Cannabidiol