Oral Anti-Inflammatory Activity of Cannabidiol, a Non-Psychoactive Constituent of Cannabis, in Acute Carrageenan-Induced Inflammation in the Rat Paw

Naunyn Schmiedebergs Arch Pharmacol. 2004 Mar;369(3):294-9. doi: 10.1007/s00210-004-0871-3. Epub 2004 Feb 12.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Cannabidiol / administration & dosage*
  • Cannabis*
  • Carrageenan / toxicity*
  • Dose-Response Relationship, Drug
  • Edema / chemically induced
  • Edema / drug therapy*
  • Edema / metabolism
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy
  • Hyperalgesia / metabolism
  • Male
  • Nitric Oxide / biosynthesis
  • Rats
  • Rats, Wistar

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cannabidiol
  • Nitric Oxide
  • Carrageenan