Cannabis is frequently used as a co-medication by patients with cancer or chronic inflammatory diseases such as rheumatoid arthritis [1]. Accordingly, it has been shown that cannabinoids modulate apoptotic signalling, and the activity of pro-inflammatory factors [2]. The advantages of using whole plant preparations compared to pure cannabinoids, particularly in terms of less toxic side effects, has also been reported [1]. Traditional Cannabis preparations (TCPs) such as tinctures (e.g. British pharmacopoeia 1932) may thus combine useful biological effects of cannabinoid and non-cannabinoid constituents. We therefore tested the ability of TCPs to produce cytotoxicity in an in vitro (MTT) assay and also to modulate the activation of Nuclear Factor kappa B (NF-κB, IL-6 reporter gene luciferase assay). Our results showed that TCP toxicity in cancer cells (HeLa, PC12) increased in proportion with the cannabinoid content of the starting material and decreasing solvent polarity. The LC15 of Cannabis tinctures were between 100µl/ml for high polar extracts and low cannabinoid content and <0.02µl/ml for lipophilic extracts of high cannabinoid material. Crude extracts/tinctures had a moderate NF-κB-inhibiting effect at non-toxic concentrations in HeLaluc cells, whereas fractions thereof (specifically medium polar preparations) either activated or inhibited NF-κB more effectively at concentrations between 0.2 and 100µg/ml. 1H-NMR fingerprints with suppression of solvent signals reflected those effects distinguishing between five starting materials and the type extract. The ratio between major cannabinoid and phenolic constituents in TCPs as relevant marker for cytotoxic and anti-inflammatory effects is suggested.
Acknowledgements: William Ransom & Son Plc, European commission (grant code COOP-CT-2004–512696).
References: [1] Russo, E., Guy, G.W. (2006) Medical Hypotheses 66: 234–246. [2] Juttler, E. et al. (2004) Neuropharmacol. 47: 580–592.
