Cannabinoids Delta(9)-tetrahydrocannabinol and cannabidiol differentially inhibit the lipopolysaccharide-activated NF-kappaB and interferon-beta/STAT proinflammatory pathways in BV-2 microglial cells

J Biol Chem. 2010 Jan 15;285(3):1616-26. doi: 10.1074/jbc.M109.069294. Epub 2009 Nov 12.


Cannabinoids have been shown to exert anti-inflammatory activities in various in vivo and in vitro experimental models as well as ameliorate various inflammatory degenerative diseases. However, the mechanisms of these effects are not completely understood. Using the BV-2 mouse microglial cell line and lipopolysaccharide (LPS) to induce an inflammatory response, we studied the signaling pathways engaged in the anti-inflammatory effects of cannabinoids as well as their influence on the expression of several genes known to be involved in inflammation. We found that the two major cannabinoids present in marijuana, Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), decrease the production and release of proinflammatory cytokines, including interleukin-1beta, interleukin-6, and interferon (IFN)beta, from LPS-activated microglial cells. The cannabinoid anti-inflammatory action does not seem to involve the CB1 and CB2 cannabinoid receptors or the abn-CBD-sensitive receptors. In addition, we found that THC and CBD act through different, although partially overlapping, mechanisms. CBD, but not THC, reduces the activity of the NF-kappaB pathway, a primary pathway regulating the expression of proinflammatory genes. Moreover, CBD, but not THC, up-regulates the activation of the STAT3 transcription factor, an element of homeostatic mechanism(s) inducing anti-inflammatory events. Following CBD treatment, but less so with THC, we observed a decreased level of mRNA for the Socs3 gene, a main negative regulator of STATs and particularly of STAT3. However, both CBD and THC decreased the activation of the LPS-induced STAT1 transcription factor, a key player in IFNbeta-dependent proinflammatory processes. In summary, our observations show that CBD and THC vary in their effects on the anti-inflammatory pathways, including the NF-kappaB and IFNbeta-dependent pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cannabidiol / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Dronabinol / pharmacology*
  • Inflammation / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Interferon-beta / metabolism
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Microglia / cytology
  • Microglia / drug effects*
  • Microglia / metabolism
  • NF-kappa B / metabolism*
  • STAT Transcription Factors / metabolism


  • Intercellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • NF-kappa B
  • STAT Transcription Factors
  • Cannabidiol
  • Interferon-beta
  • Dronabinol