Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol - studies in BV-2 microglia and encephalitogenic T cells

J Basic Clin Physiol Pharmacol. 2016 May 1;27(3):289-96. doi: 10.1515/jbcpp-2015-0071.


Background: Dimethylheptyl-cannabidiol (DMH-CBD), a non-psychoactive, synthetic derivative of the phytocannabinoid cannabidiol (CBD), has been reported to be anti-inflammatory in RAW macrophages. Here, we evaluated the effects of DMH-CBD at the transcriptional level in BV-2 microglial cells as well as on the proliferation of encephalitogenic T cells.

Methods: BV-2 cells were pretreated with DMH-CBD, followed by stimulation with the endotoxin lipopolysaccharide (LPS). The expression levels of selected genes involved in stress regulation and inflammation were determined by quantitative real-time PCR. In addition, MOG35-55-reactive T cells (TMOG) were cultured with antigen-presenting cells in the presence of DMH-CBD and MOG35-55 peptide, and cell proliferation was determined by measuring [3H]thymidine incorporation.

Results: DMH-CBD treatment downregulated in a dose-dependent manner the mRNA expression of LPS-upregulated pro-inflammatory genes (Il1b, Il6, and Tnf) in BV-2 microglial cells. The expression of these genes was also downregulated by DMH-CBD in unstimulated cells. In parallel, DMH-CBD upregulated the expression of genes related to oxidative stress and glutathione homeostasis such as Trb3, Slc7a11/xCT, Hmox1, Atf4, Chop, and p8 in both stimulated and unstimulated microglial cells. In addition, DMH-CBD dose-dependently inhibited MOG35-55-induced TMOG proliferation.

Conclusions: The results show that DMH-CBD has similar anti-inflammatory properties to those of CBD. DMH-CBD downregulates the expression of inflammatory cytokines and protects the microglial cells by inducing an adaptive cellular response against inflammatory stimuli and oxidative injury. In addition, DMH-CBD decreases the proliferation of pathogenic activated TMOG cells.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cannabidiol / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Down-Regulation / drug effects
  • Encephalitis / drug therapy*
  • Encephalitis / metabolism
  • Gene Expression / drug effects
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Microglia / drug effects*
  • Microglia / metabolism
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Up-Regulation / drug effects


  • Anti-Inflammatory Agents
  • Cytokines
  • Cannabidiol