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Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw

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Abstract

Cannabidiol, the major non-psychoactive component of marijuana, has various pharmacological actions of clinical interest. It is reportedly effective as an anti-inflammatory and anti-arthritic in murine collagen-induced arthritis. The present study examined the anti-inflammatory and anti-hyperalgesic effects of cannabidiol, administered orally (5–40 mg/kg) once a day for 3 days after the onset of acute inflammation induced by intraplantar injection of 0.1 ml carrageenan (1% w/v in saline) in the rat. At the end of the treatment prostaglandin E2 (PGE2) was assayed in the plasma, and cyclooxygenase (COX) activity, production of nitric oxide (NO; nitrite/nitrate content), and of other oxygen-derived free radicals (malondialdehyde) in inflamed paw tissues. All these markers were significantly increased following carrageenan.

Thermal hyperalgesia, induced by carrageenan and assessed by the plantar test, lasted 7 h. Cannabidiol had a time- and dose-dependent anti-hyperalgesic effect after a single injection. Edema following carrageenan peaked at 3 h and lasted 72 h; a single dose of cannabidiol reduced edema in a dose-dependent fashion and subsequent daily doses caused further time- and dose-related reductions.

There were decreases in PGE2 plasma levels, tissue COX activity, production of oxygen-derived free radicals, and NO after three doses of cannabidiol. The effect on NO seemed to depend on a lower expression of the endothelial isoform of NO synthase. In conclusion, oral cannabidiol has a beneficial action on two symptoms of established inflammation: edema and hyperalgesia.

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Acknowledgements

This work was supported by grants from the Italian Ministry for Education, University and Research (M.I.U.R.). The authors thank GW Pharma for kindly supplying cannabidiol.

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Authors and Affiliations

  1. Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Piazza della Scienza 2, 20126, Milan, Italy

    Barbara Costa, Silvia Conti, Anna Elisa Trovato & Gabriella Giagnoni

  2. Dipartimento di Farmacologia, Università di Milano, Via Vanvitelli 32, 20129, Milan, Italy

    Mariapia Colleoni & Chiara Franke

  3. Dipartimento di Biologia Strutturale e Funzionale, Sezione di Farmacologia, Università dell’Insubria, Via A. da Giussano, 21052, Busto Arsizio, Varese, Italy

    Daniela Parolaro

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  1. Barbara Costa
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  2. Mariapia Colleoni
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  3. Silvia Conti
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  4. Daniela Parolaro
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  5. Chiara Franke
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  6. Anna Elisa Trovato
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  7. Gabriella Giagnoni
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Correspondence to Barbara Costa.

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Costa, B., Colleoni, M., Conti, S. et al. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn-Schmiedeberg's Arch Pharmacol 369, 294–299 (2004). https://doi.org/10.1007/s00210-004-0871-3

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  • DOI: https://doi.org/10.1007/s00210-004-0871-3

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