Cannabinoid 2 (CB2) receptor agonism reduces lithium chloride-induced vomiting in Suncus murinus and nausea-induced conditioned gaping in rats

Eur J Pharmacol. 2016 Sep 5;786:94-99. doi: 10.1016/j.ejphar.2016.06.001. Epub 2016 Jun 2.


We aimed to investigate the potential anti-emetic and anti-nausea properties of targeting the cannabinoid 2 (CB2) receptor. We investigated the effect of the selective CB2 agonist, HU-308, on lithium chloride- (LiCl) induced vomiting in Suncus murinus (S. murinus) and conditioned gaping (nausea-induced behaviour) in rats. Additionally, we determined whether these effects could be prevented by pretreatment with AM630 (a selective CB2 receptor antagonist/inverse agonist). In S. murinus, HU-308 (2.5, 5mg/kg, i.p.) reduced, but did not completely block, LiCl-induced vomiting; an effect that was prevented with AM630. In rats, HU-308 (5mg/kg, i.p.) suppressed, but did not completely block, LiCl-induced conditioned gaping to a flavour; an effect that was prevented by AM630. These findings are the first to demonstrate the ability of a selective CB2 receptor agonist to reduce nausea in animal models, indicating that targeting the CB2 receptor may be an effective strategy, devoid of psychoactive effects, for managing toxin-induced nausea and vomiting.

Keywords: AM630; AM630 (PubChem CID: 4302963); Acute nausea; CB(2) receptor; Conditioned gaping; HU-308; HU-308 (PubChem CID: 9844711); Lithium chloride (PubChem CID: 433294); Vomiting.

MeSH terms

  • Animals
  • Antiemetics / pharmacology
  • Antiemetics / therapeutic use
  • Cannabinoids / pharmacology*
  • Cannabinoids / therapeutic use
  • Conditioning, Psychological / drug effects*
  • Indoles / pharmacology
  • Lithium Chloride / adverse effects*
  • Male
  • Nausea / chemically induced
  • Nausea / drug therapy*
  • Nausea / metabolism
  • Nausea / physiopathology
  • Rats
  • Receptor, Cannabinoid, CB2 / agonists*
  • Receptor, Cannabinoid, CB2 / metabolism
  • Shrews*
  • Vomiting / chemically induced
  • Vomiting / drug therapy*
  • Vomiting / metabolism


  • Antiemetics
  • Cannabinoids
  • Indoles
  • Receptor, Cannabinoid, CB2
  • HU 308
  • Lithium Chloride
  • iodopravadoline