HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

The potent emetogenic effects of the endocannabinoid, 2-AG (2-arachidonoylglycerol) are blocked by delta(9)-tetrahydrocannabinol and other cannnabinoids.

Abstract
Cannabinoids, including the endogenous cannabinoid or endocannabinoid, anandamide, modulate several gastrointestinal functions. To date, the gastrointestinal effects of the second putative endocannabinoid 2-arachidonoylglycerol (2-AG) have not been studied. In the present study using a shrew (Cryptotis parva) emetic model, 2-AG (0.25-10 mg/kg, i.p.) potently and dose-dependently increased vomiting frequency (ED(50) = 1.13 mg/kg) and the number of animals vomiting (ED(50) = 0.48 mg/kg). In contrast, neither anandamide (2.5-20 mg/kg) nor methanandamide (5-10 mg/kg) induced a dose-dependent emetogenic response, but both could partially block the induced emetic effects. Delta(9)-Tetrahydrocannabinol and its synthetic analogs reduced 2-AG-induced vomiting with the rank order potency: CP 55,940 > WIN 55,212-2 > Delta(9)-tetrahydrocannabinol. The nonpsychoactive cannabinoid, cannabidiol, was inactive. Nonemetic doses of SR 141716A (1-5 mg/kg) also blocked 2-AG-induced vomiting. The 2-AG metabolite arachidonic acid also caused vomiting. Indomethacin, a cyclooxygenase inhibitor, blocked the emetogenic effects of both arachidonic acid and 2-AG. CP 55,940 also blocked the emetic effects of arachidonic acid. 2-AG (0.25-10 mg/kg) reduced spontaneous locomotor activity (ED(50) = 11 mg/kg) and rearing frequency (ED(50) = 4.3 mg/kg) in the shrew, whereas such doses of both anandamide and methanandamide had no effect on locomotor parameters. The present study indicates that: 1) 2-AG is an efficacious endogenous emetogenic cannabinoid involved in vomiting circuits, 2) the emetic action of 2-AG and the antiemetic effects of tested cannabinoids are mediated via CB(1) receptors, and 3) the emetic effects of 2-AG occur in lower doses relative to its locomotor suppressant actions.
AuthorsNissar A Darmani
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 300 Issue 1 Pg. 34-42 (Jan 2002) ISSN: 0022-3565 [Print] United States
PMID11752094 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antiemetics
  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Cyclohexanols
  • Emetics
  • Endocannabinoids
  • Glycerides
  • Piperidines
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • methanandamide
  • rimonabant
  • 2-arachidonylglycerol
  • Dronabinol
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
  • anandamide
Topics
  • Animals
  • Antiemetics (pharmacology)
  • Arachidonic Acids (pharmacology)
  • Cannabinoid Receptor Modulators
  • Cannabinoids (pharmacology)
  • Cyclohexanols (pharmacology)
  • Dose-Response Relationship, Drug
  • Dronabinol (pharmacology)
  • Emetics (antagonists & inhibitors, pharmacology)
  • Endocannabinoids
  • Female
  • Glycerides (antagonists & inhibitors, pharmacology)
  • Humans
  • Male
  • Motor Activity (drug effects)
  • Piperidines (pharmacology)
  • Polyunsaturated Alkamides
  • Pyrazoles (pharmacology)
  • Receptors, Cannabinoid
  • Receptors, Drug (antagonists & inhibitors)
  • Shrews

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: