title: Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways.
abstract: 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.
authors.affiliation: TNO Pharma, Utrechtseweg 48, PZeist, The Netherlands. Verhoeckx@pharma.tno.nl
authors.forename: Kitty C M
authors.initials: KC
authors.lastname: Verhoeckx
authors.forename: Henrie A A J
authors.initials: HA
authors.lastname: Korthout
authors.forename: A P
authors.initials: AP
authors.lastname: van Meeteren-Kreikamp
authors.forename: Karl A
authors.initials: KA
authors.lastname: Ehlert
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Jan
authors.initials: J
authors.lastname: van der Greef
authors.forename: Richard J T
authors.initials: RJ
authors.lastname: Rodenburg
authors.forename: Renger F
authors.initials: RF
authors.lastname: Witkamp
mesh_terms: D002188:Cannabis / Q000737:chemistry* / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D007155:Immunologic Factors; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D007155:Immunologic Factors; D010936:Plant Extracts; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D014409:Tumor Necrosis Factor-alpha; D013759:Dronabinol; D000242:Cyclic AMP; D010738:Type C Phospholipases