Interaction between non-psychotropic cannabinoids in marihuana: effect of cannabigerol (CBG) on the anti-nausea or anti-emetic effects of cannabidiol (CBD) in rats and shrews
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The interaction between two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), which have been reported to act as a 5-hydroxytryptamine 1A (5-HT1A) agonist and antagonist, respectively, was evaluated.
To evaluate the potential of CBG to reverse the anti-nausea, anti-emetic effects of CBD.
Materials and methods
In experiment 1, rats were pre-treated with CBG (0.0, 1, 5, and 10 mg/kg, ip), 15 min prior to being treated with CBD (experiment 1a: VEH or 5 mg/kg, ip) or 8-OH-DPAT (experiment 1b: VEH or 0.01 mg/kg, ip). Thirty minutes later, all rats received a pairing of 0.1% saccharin solution and LiCl (20 ml/kg of 0.15 M, ip). Seventy-two hours later, the rats received a drug-free taste reactivity test with saccharin to evaluate the effects of the treatments on the establishment of conditioned gaping reactions (a model of nausea). As well, conditioned saccharin avoidance was measured. In experiment 2, Suncus murinus were injected with CBG (5 mg/kg, ip) or VEH 15 min prior to CBD (5 mg/kg) or VEH and 30 min later were injected with LiCl (60 ml/kg of 0.15 M, i.p.), and the number of vomiting episodes were measured.
CBD (5 mg/kg) suppressed conditioned gaping in rats and vomiting in shrews, which were reversed by pre-treatment with all doses of CBG. CBG also prevented the anti-nausea effects of 8-OH-DPAT.
Interactions between moderate doses of CBG and CBD may oppose one another at the 5-HT1A receptor in the regulation of nausea and vomiting.
KeywordsNausea Vomiting Cannabinoids Cannabigerol Cannabidiol Serotonin 5-HT1A Phytocannabinoid
The following research was supported by research grants from the Natural Sciences and Engineering Research Council (NSERC) of Canada to LAP, a scholarship from NSERC to EMR, and a grant from NIDA (9789) to RM and RGP. For reprints please contact email@example.com.
- Gaoni Y, Mechoulam R (1964b) The structure and synthesis of cannabigerol, a new hashish constituent. Proc Chem Soc 82Google Scholar
- Kwiatkowska M, Parker LA, Burton P, Mechoulam R (2004) A comparative analysis of the potential of cannabinoids and ondansetron to suppress cisplatin-induced emesis in the Suncus murinus (house musk shrew). Psychopharmacol 174:254–259Google Scholar
- Limebeer CL, Parker LA (2003) The 5-HT1A agonist 8-OH-DPAT dose-dependently interferes with the establishment and the expression of lithium-induced conditioned rejection reactions in rats. Psychopharmacol 166:120–126Google Scholar
- Limebeer CL, Vemuri VK, Bedard H, Lang ST, Ossenkopp KP, Makriyannis A, Parker LA (2010) Inverse agonism of cannabinoid CB1 receptors potentiates LiCl-induced nausea in the conditioned gaping model in rats. Br J Pharm (in press)Google Scholar
- Maor Y, Morowitz M, Gallily R, Mechoulam R (2005) Cannabigerol-dimethyl heptyl (CBG-DMH), a synthetic cannabinoid with hypotensive and vasorelaxant properties. Presented at the symposium of the International Cannabinoid Research Society, Clearwater, FL, JuneGoogle Scholar
- Parker LA, Limebeer CL (2008) Cannabinoids and the management of nausea and vomiting. In: Kofalvi A (ed) Cannabinoids and the brain. Springer, New YorkGoogle Scholar
- Parker LA, Mechoulam R, Schlievert C, Abbott L, Fudge ML, Burton P (2003) Effects of cannabinoids on lithium-induced conditioned rejection reactions in a rat model of nausea. Psychopharmacol 166:156–162Google Scholar
- Parker LA, Kwiatkowska M, Mechoulam R (2006) Delta-9-tetrahydrocannabinol and cannabidiol, but not ondansetron, interfere with conditioned retching reactions elicited by a lithium-paired context in Suncus murinus: an animal model of anticipatory nausea and vomiting. Physiol Behav 87:61–71CrossRefGoogle Scholar
- Parker LA, Limebeer CL, Rana SA (2008) Conditioned nausea in rats: assessment by conditioned disgust reactions, rather than conditioned taste avoidance. Can J Exp Psychol 62:189–209Google Scholar
- Parker, LA., Limebeer CL, Rock EM, Litt DL, Kwiatkowska M., and Piomelli D. (2009) The FAAH inhibitor URB-597 interferes with cisplatin- and nicotine- induced vomiting in the Suncus murinus (house musk shrew). Physiol Behav 97: 121-124Google Scholar
- Pertwee RG (2004) In: DiMarzo V (ed) The pharmacology and therapeutic potential of cannabidiol, in cannabinoids. Kluwer, New YorkGoogle Scholar
- Rock EM, Limebeer CL, Fletcher PJ, Mechoulam R, Parker LA (2010). Cannabidiol (the non-psychoactive component of cannabis) may act as a 5-HT1A auto-receptor agonist to reduce toxin-induced nausea and vomiting. Poster presented at the Society for Neuroscience meeting, San Diego, CAGoogle Scholar