Cannabidiol inhibits the hyperphagia induced by cannabinoid-1 or serotonin-1A receptor agonists

Pharmacol Biochem Behav. 2011 Apr;98(2):268-72. doi: 10.1016/j.pbb.2011.01.007. Epub 2011 Jan 14.


Δ9-THC is a component of Cannabis sativa that increases food intake in animals and humans, an effect prevented by selective CB1 receptor antagonists. Cannabidiol (CBD) is another constituent of this plant that promotes several opposite neuropharmacological effects compared to Δ9-THC. CBD mechanisms of action are still not clear, but under specific experimental conditions it can antagonize the effects of cannabinoid agonists, block the reuptake of anandamide and act as an agonist of 5-HT1A receptors. Since both the cannabinoid and serotoninergic systems have been implicated in food intake control, the aim of the present work was to investigate the effects caused by CBD on hyperphagia induced by agonists of CB1 or 5-HT1A receptors. Fed or fasted Wistar rats received intraperitoneal (i.p.) injections of CBD (1, 10 and 20 mg/kg) and food intake was measured 30 min later for 1 h. Moreover, additional fed or fasted groups received, after pretreatment with CBD (20 mg/kg) or vehicle, i.p. administration of vehicle, a CB1 receptor agonist WIN55,212-2 (2 mg/kg) or a 5-HT1A receptor agonist 8-OH-DPAT (1 mg/kg) and were submitted to the food intake test for 1 h. CBD by itself did not change food intake in fed or fasted rats. However, it prevented the hyperphagic effects induced by WIN55,212-2 or 8-OH-DPAT. These results show that CBD can interfere with food intake changes induced by a CB1 or 5-HT1A receptor agonist, suggesting that its role as a possible food intake regulator should be further investigate.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / administration & dosage
  • Animals
  • Benzoxazines / administration & dosage
  • Cannabidiol / administration & dosage*
  • Drug Interactions
  • Eating / drug effects*
  • Fasting
  • Hyperphagia / chemically induced*
  • Hyperphagia / prevention & control*
  • Male
  • Morpholines / administration & dosage
  • Naphthalenes / administration & dosage
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / agonists*
  • Serotonin 5-HT1 Receptor Agonists / administration & dosage*


  • Benzoxazines
  • Morpholines
  • Naphthalenes
  • Receptor, Cannabinoid, CB1
  • Serotonin 5-HT1 Receptor Agonists
  • Cannabidiol
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • 8-Hydroxy-2-(di-n-propylamino)tetralin