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

42 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

Keywords

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

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