TY - JOUR
T1 - Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways
AU - Verhoeckx, Kitty C.M.
AU - Korthout, Henrie A.A.J.
AU - Van Meeteren-Kreikamp, A. P.
AU - Ehlert, Karl A.
AU - Wang, Mei
AU - Van Der Greef, Jan
AU - Rodenburg, Richard J.T.
AU - Witkamp, Renger F.
PY - 2006/4
Y1 - 2006/4
N2 - There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Δ9-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 Δ9-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-α) 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-α 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.
AB - There is a great interest in the pharmacological properties of cannabinoid like compounds that are not linked to the adverse effects of Δ9-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 Δ9-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-α) 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-α 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.
KW - Δ-tetrahydrocanabinoid
KW - Δ-tetrahydrocanabinoid acid
KW - cAMP
KW - Cannabis sativa
KW - Inflammation
KW - PC-PLC
KW - TNF-alpha
UR - http://www.scopus.com/inward/record.url?scp=33644551536&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2005.10.002
DO - 10.1016/j.intimp.2005.10.002
M3 - Article
C2 - 16504929
AN - SCOPUS:33644551536
SN - 1567-5769
VL - 6
SP - 656
EP - 665
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 4
ER -