Print Email Facebook Twitter Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways 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 Author Verhoeckx, K.C.M. Korthout, H.A.A.J. van Meeteren-Kreikamp, A.P. Ehlert, K.A. Wang, M. van der Greef, J. Rodenburg, R.J.T. Witkamp, R.F. TNO Kwaliteit van Leven Publication year 2006 Abstract 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. © 2005 Elsevier B.V. All rights reserved. Subject HealthAnalytical researchBiomedical researchΔ9-tetrahydrocanabinoidΔ9-tetrahydrocanabinoid acidcAMPCannabis sativaInflammationPC-PLCTNF-alpha1 (2,4 dichlorophenyl) 5 (4 iodophenyl) 4 methyl n morpholino 1h pyrazole 3 carboxamide6 iodo 3 (4 methoxybenzoyl) 2 methyl 1 (2 morpholinoethyl)indoleBeta 2 adrenergic receptor stimulating agentCannabidiolCannabidiolic acidCannabinoid 1 receptorCannabinoid 2 receptorCannabinoid derivativeCannabisDelta 9 tetrahydrocannabinoid acidDronabinolImmunomodulating agentLipopolysaccharidePhosphatidylcholinePhospholipase CTumor necrosis factor alphaUnclassified drugZilpaterolCell strain U937Concentration responseControlled studyCytokine productionDown regulationDrug effectDrug mechanismEnzyme activityHeatingHuman cellImmunomodulationImmunopharmacologyImmunostimulationLong term exposureMacrophageMetabolismProtein inductionProtein synthesis regulationSupernatantUpregulationCannabisCell LineCells, CulturedCyclic AMPDose-Response Relationship, DrugHeatHumansImmunologic FactorsMacrophage ActivationMacrophagesPhospholipase CPlant ExtractsReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Signal TransductionTetrahydrocannabinolTumor Necrosis Factor-alpha To reference this document use: http://resolver.tudelft.nl/uuid:56538900-09c2-4e2c-92f5-877c7dfc22b4 DOI https://doi.org/10.1016/j.intimp.2005.10.002 TNO identifier 239212 ISSN 1567-5769 Source International Immunopharmacology, 6 (4), 656-665 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.