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Title: Cannabis extracts for medicinal use : chemical profiling and in vitro anti-inflammatory and cytotoxic effects
Author: Peschel, Wieland
ISNI:       0000 0004 2682 3849
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2009
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Cannabis is used as a co-medication by patients with cancer or chronic inflammatory diseases. Anti-inflammatory effects of Δ9-tetrahydrocannabinol (THC) and other cannabinoids are frequently linked to the modulation of the Nuclear Factor kappaB (NF-KB). Advantages of using whole plant preparations have also been reported. The composition of preparations such as traditional hydroethanolic cannabis extracts (CE) varies due to the type of plant and preparation. This dissertation aimed to contribute insights into chemical standardisation and pharmacological profiling as part of a European Project developing CE medicines. The chemical profile of CE from different starting materials was determined using HPLC and 1H-NMR. Their pharmacological properties were measured as the ability to modulate the activation of NF-KB in IL-6 reporter gene stably transfected HeLa cells, to induce in vitro cytotoxicity in cancer cell lines (MTT-assay) and to activate caspase 3/7. The effect of pure cannabinoids and their combinations with plant phenolics and classical anti-inflammatory/cytotoxic drugs was also investigated. The HPLC/NMR profiles showed cannabinoid dominance even in polar extracts and a substantial portion of cannabinoid acids depending on CE age and storage. Markers for standardisation indicating plant type, solvent and stability -such as the ratio between neutral and carboxylated cannabinoids- are proposed. CE toxicity correlated with the total cannabinoid but not necessarily the THC content. Also all main pure phytocannabinoids proved to be equally toxic. Some CE were more toxic than pure phytocannabinoids, other CE reduced the effects of the compounds alone. In most cases toxicity correlated with the effect on NF-KB activation and also with the caspase 3/7 activation indicating apoptotic signalling. It appears also that the NF-KB activity of cannabinoids/CE is neither CB1 nor CB2 receptor dependent. The results show that there is a strong link between NF-KB and the toxic effect of cannabis in cancer cell lines. The in vitro effect of CE can differ from that of pure cannabinoids and is more influenced by factors other than the chemotype. Thus standardised CE of plants with predominantly non-psychotropic cannabinoids such as cannabidiol or cannabigerol may be as useful as traditional THC-type derived CE for the co-treatment in cancer and inflammatory diseases.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available