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

• Published in: International immunopharmacology Vol. 6; no. 4
• Main Authors: Verhoeckx, K.C.M, Korthout, H.A.A.J, Meeteren-Kreikamp, A.P., van, Ehlert, K.A, Wang, M, Greef, J., de, Rodenburg, R.J.T, Witkamp, R.F
• Format: Journal Article
• Published: 2006
• Subjects: activation; brain; cell-line; cytokine; differentiation; human alveolar macrophages; kappa-b; lipopolysaccharide; phospholipase-c; transcriptomics
• ISSN: 1567-5769; 1878-1705

There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of ¿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 ¿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-a) 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-a 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