European Journal of Pharmacology. 556(1):75–83, FEBRUARY 5, 2007
DOI: 10.1016/j.ejphar.2006.11.006
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PMID: 17157290
Issn Print: 0014-2999
Publication Date: February 5, 2007
The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain
Barbara Costa;Anna Trovato;Francesca Comelli;Gabriella Giagnoni;Mariapia Colleoni;
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aDepartment of Biotechnology and Bioscience, University of Milano-Bicocca, piazza della Scienza 2, 20126 Milano, ItalybDepartment of Pharmacology, Chemotherapy and Medical Toxicology, University of Milano, via Vanvitelli 32, 20129 Milano, Italy
Abstract
Cannabidiol, the major psycho-inactive component of cannabis, has substantial anti-inflammatory and immunomodulatory effects. This study investigated its therapeutic potential on neuropathic (sciatic nerve chronic constriction) and inflammatory pain (complete Freund's adjuvant intraplantar injection) in rats. In both models, daily oral treatment with cannabidiol (2.5–20 mg/kg to neuropathic and 20 mg/kg to adjuvant-injected rats) from day 7 to day 14 after the injury, or intraplantar injection, reduced hyperalgesia to thermal and mechanical stimuli. In the neuropathic animals, the anti-hyperalgesic effect of cannabidiol (20 mg/kg) was prevented by the vanilloid antagonist capsazepine (10 mg/kg, i.p.), but not by cannabinoid receptor antagonists. Cannabidiol's activity was associated with a reduction in the content of several mediators, such as prostaglandin E2 (PGE2), lipid peroxide and nitric oxide (NO), and in the over-activity of glutathione-related enzymes. Cannabidiol only reduced the over-expression of constitutive endothelial NO synthase (NOS), without significantly affecting the inducible form (iNOS) in inflamed paw tissues. Cannabidiol had no effect on neuronal and iNOS isoforms in injured sciatic nerve. The compound's efficacy on neuropathic pain was not accompanied by any reduction in nuclear factor-κB (NF-κB) activation and tumor necrosis factor α (TNFα) content. The results indicate a potential for therapeutic use of cannabidiol in chronic painful states.
