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
Health
Analytical research
Biomedical research
Δ9-tetrahydrocanabinoid
Δ9-tetrahydrocanabinoid acid
cAMP
Cannabis sativa
Inflammation
PC-PLC
TNF-alpha
1 (2,4 dichlorophenyl) 5 (4 iodophenyl) 4 methyl n morpholino 1h pyrazole 3 carboxamide
6 iodo 3 (4 methoxybenzoyl) 2 methyl 1 (2 morpholinoethyl)indole
Beta 2 adrenergic receptor stimulating agent
Cannabidiol
Cannabidiolic acid
Cannabinoid 1 receptor
Cannabinoid 2 receptor
Cannabinoid derivative
Cannabis
Delta 9 tetrahydrocannabinoid acid
Dronabinol
Immunomodulating agent
Lipopolysaccharide
Phosphatidylcholine
Phospholipase C
Tumor necrosis factor alpha
Unclassified drug
Zilpaterol
Cell strain U937
Concentration response
Controlled study
Cytokine production
Down regulation
Drug effect
Drug mechanism
Enzyme activity
Heating
Human cell
Immunomodulation
Immunopharmacology
Immunostimulation
Long term exposure
Macrophage
Metabolism
Protein induction
Protein synthesis regulation
Supernatant
Upregulation
Cannabis
Cell Line
Cells, Cultured
Cyclic AMP
Dose-Response Relationship, Drug
Heat
Humans
Immunologic Factors
Macrophage Activation
Macrophages
Phospholipase C
Plant Extracts
Receptor, Cannabinoid, CB1
Receptor, Cannabinoid, CB2
Signal Transduction
Tetrahydrocannabinol
Tumor 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