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

K.C.M. Verhoeckx, H.A.A.J. Korthout, A.P. van Meeteren-Kreikamp, K.A. Ehlert, M. Wang, J. de Greef, R.J.T. Rodenburg, R.F. Witkamp

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Scopus)

Abstract

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
Original languageEnglish
Pages (from-to)656-665
JournalInternational Immunopharmacology
Volume6
Issue number4
DOIs
Publication statusPublished - 2006

Fingerprint

Cannabinoid Receptor CB2
Dronabinol
Cannabis
Acids
Tumor Necrosis Factor-alpha
Macrophages
Cannabinoids
Metabolic Networks and Pathways
Heating
Pharmacology
phosphatidylcholine-specific phospholipase C

Keywords

  • human alveolar macrophages
  • phospholipase-c
  • cell-line
  • kappa-b
  • cytokine
  • lipopolysaccharide
  • activation
  • brain
  • transcriptomics
  • differentiation

Cite this

Verhoeckx, K.C.M. ; Korthout, H.A.A.J. ; van Meeteren-Kreikamp, A.P. ; Ehlert, K.A. ; Wang, M. ; de Greef, J. ; Rodenburg, R.J.T. ; Witkamp, R.F. / Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated bu CB1 en CB2 receptor coupled pathways. In: International Immunopharmacology. 2006 ; Vol. 6, No. 4. pp. 656-665.
@article{6d718070da894a0ba1a13745d7e9ad53,
title = "Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated bu CB1 en 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 ¿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",
keywords = "human alveolar macrophages, phospholipase-c, cell-line, kappa-b, cytokine, lipopolysaccharide, activation, brain, transcriptomics, differentiation",
author = "K.C.M. Verhoeckx and H.A.A.J. Korthout and {van Meeteren-Kreikamp}, A.P. and K.A. Ehlert and M. Wang and {de Greef}, J. and R.J.T. Rodenburg and R.F. Witkamp",
year = "2006",
doi = "10.1016/j.intimp.2005.10.002",
language = "English",
volume = "6",
pages = "656--665",
journal = "International Immunopharmacology",
issn = "1567-5769",
publisher = "Elsevier",
number = "4",

}

Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated bu CB1 en CB2 receptor coupled pathways. / Verhoeckx, K.C.M.; Korthout, H.A.A.J.; van Meeteren-Kreikamp, A.P.; Ehlert, K.A.; Wang, M.; de Greef, J.; Rodenburg, R.J.T.; Witkamp, R.F.

In: International Immunopharmacology, Vol. 6, No. 4, 2006, p. 656-665.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated bu CB1 en CB2 receptor coupled pathways

AU - Verhoeckx, K.C.M.

AU - Korthout, H.A.A.J.

AU - van Meeteren-Kreikamp, A.P.

AU - Ehlert, K.A.

AU - Wang, M.

AU - de Greef, J.

AU - Rodenburg, R.J.T.

AU - Witkamp, R.F.

PY - 2006

Y1 - 2006

N2 - 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

AB - 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

KW - human alveolar macrophages

KW - phospholipase-c

KW - cell-line

KW - kappa-b

KW - cytokine

KW - lipopolysaccharide

KW - activation

KW - brain

KW - transcriptomics

KW - differentiation

U2 - 10.1016/j.intimp.2005.10.002

DO - 10.1016/j.intimp.2005.10.002

M3 - Article

VL - 6

SP - 656

EP - 665

JO - International Immunopharmacology

JF - International Immunopharmacology

SN - 1567-5769

IS - 4

ER -