Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 369, Issue 3, pp 294–299 | Cite as

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

  • Barbara CostaEmail author
  • Mariapia Colleoni
  • Silvia Conti
  • Daniela Parolaro
  • Chiara Franke
  • Anna Elisa Trovato
  • Gabriella Giagnoni
Original Article


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.


Cannabinoids Cannabidiol Carrageenan Inflammation Hyperalgesia COX system NO system 



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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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Barbara Costa
    • 1
    Email author
  • Mariapia Colleoni
    • 2
  • Silvia Conti
    • 1
  • Daniela Parolaro
    • 3
  • Chiara Franke
    • 2
  • Anna Elisa Trovato
    • 1
  • Gabriella Giagnoni
    • 1
  1. 1.Dipartimento di Biotecnologie e BioscienzeUniversità di Milano-BicoccaMilanItaly
  2. 2.Dipartimento di FarmacologiaUniversità di MilanoMilanItaly
  3. 3.Dipartimento di Biologia Strutturale e Funzionale, Sezione di FarmacologiaUniversità dell’InsubriaBusto Arsizio, VareseItaly

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