Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways

Int Immunopharmacol. 2006 Apr;6(4):656-65. doi: 10.1016/j.intimp.2005.10.002. Epub 2005 Nov 7.


There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Delta(9)-tetrahydrocannabinol (THC), e.g. psychoactive properties. The present paper describes the potential immuno-modulating activity of unheated Cannabis sativa extracts and its main non-psychoactive constituent Delta(9)-tetrahydrocanabinoid acid (THCa). By heating Cannabis extracts, THCa was shown to be converted into THC. Unheated Cannabis extract and THCa were able to inhibit the tumor necrosis factor alpha (TNF-alpha) levels in culture supernatants from U937 macrophages and peripheral blood macrophages after stimulation with LPS in a dose-dependent manner. This inhibition persisted over a longer period of time, whereas after prolonged exposure time THC and heated Cannabis extract tend to induce the TNF-alpha level. Furthermore we demonstrated that THCa and THC show distinct effects on phosphatidylcholine specific phospholipase C (PC-PLC) activity. Unheated Cannabis extract and THCa inhibit the PC-PLC activity in a dose-dependent manner, while THC induced PC-PLC activity at high concentrations. These results suggest that THCa and THC exert their immuno-modulating effects via different metabolic pathways.

MeSH terms

  • Cannabis / chemistry*
  • Cannabis / immunology*
  • Cell Line
  • Cells, Cultured
  • Cyclic AMP / pharmacology
  • Dose-Response Relationship, Drug
  • Dronabinol / pharmacology*
  • Hot Temperature
  • Humans
  • Immunologic Factors*
  • Macrophage Activation / drug effects
  • Macrophages / drug effects
  • Macrophages / immunology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / drug effects*
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB2 / drug effects*
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • Type C Phospholipases / metabolism


  • Immunologic Factors
  • Plant Extracts
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Tumor Necrosis Factor-alpha
  • Dronabinol
  • Cyclic AMP
  • Type C Phospholipases