A selective CB2 receptor agonist reduced both vomiting and nausea-related behavior in animal models, offering a potential anti-nausea pathway that avoids the psychoactive effects of THC.
Read this if you are interested in cannabis-based nausea treatments that avoid the psychoactive effects of THC.
First selective CB2 agonist shown to reduce both vomiting and nausea behavior in animal models.
What the researchers found
Researchers tested HU-308, a compound that selectively activates CB2 receptors (unlike THC, which primarily activates CB1 receptors in the brain), for anti-nausea and anti-vomiting effects.
In shrews (Suncus murinus, one of the few small animals that can vomit), HU-308 reduced lithium chloride-induced vomiting at doses of 2.5 and 5 mg/kg. In rats, the same compound suppressed conditioned gaping, a behavior that specifically models nausea rather than vomiting.
Both effects were blocked when animals were pre-treated with AM630, a selective CB2 receptor antagonist, confirming the effects were specifically mediated through CB2 receptors.
These are the first published findings demonstrating that a selective CB2 agonist can reduce nausea in animal models.
Why it matters
Cannabis-based anti-nausea treatments currently work through CB1 receptors, which also produce psychoactive effects like euphoria, impaired memory, and altered coordination. If CB2-targeted compounds can reduce nausea without these side effects, they could offer a cleaner therapeutic option for chemotherapy patients and others dealing with severe nausea.
The numbers in context
HU-308 at 2.5 and 5 mg/kg reduced vomiting in shrews. HU-308 at 5 mg/kg suppressed conditioned gaping in rats. Both effects were blocked by the CB2 antagonist AM630.
How the study worked
Two animal models were used. Lithium chloride-induced vomiting was measured in Suncus murinus (house musk shrews). Conditioned gaping, a validated model of nausea-related behavior, was measured in rats. The selective CB2 agonist HU-308 was tested at multiple doses, and the CB2 antagonist AM630 was used to confirm receptor specificity.
What this study cannot tell us
HU-308 reduced but did not completely block vomiting or nausea-related behavior. These are animal models, and translation to human nausea is uncertain. The study did not compare CB2 agonist efficacy to existing anti-nausea treatments or CB1-based cannabinoids.
How to read the evidence
Preliminary evidence from animal models. While the receptor specificity is well demonstrated, human translation has not been tested.
When this study was published
Published in 2016. CB2-targeted therapeutics remain an active area of drug development.
The bigger picture
Anti-nausea drug development has largely focused on CB1 receptors because of THC's well-known anti-emetic properties. This study opens a parallel pathway through CB2, which is primarily expressed in immune cells and peripheral tissues rather than the brain regions responsible for psychoactive effects.
Questions still open
- Would CB2 agonists be effective enough for severe chemotherapy-induced nausea on their own? Could combining CB2 agonists with low-dose CB1 activation produce better anti-nausea effects with fewer psychoactive side effects? What is the mechanism by which CB2 activation reduces nausea?
Common questions
Can you get anti-nausea effects from cannabis without getting high?
What is the difference between CB1 and CB2 receptors?
Read the original research
Cannabinoid 2 (CB2) receptor agonism reduces lithium chloride-induced vomiting in Suncus murinus and nausea-induced conditioned gaping in rats.
European journal of pharmacology, 786, 94-99
Citation
Rock, Erin M; Boulet, Nathalie; Limebeer, Cheryl L; Mechoulam, Raphael; Parker, Linda A. (2016). Cannabinoid 2 (CB2) receptor agonism reduces lithium chloride-induced vomiting in Suncus murinus and nausea-induced conditioned gaping in rats.. European journal of pharmacology, 786, 94-99. https://doi.org/10.1016/j.ejphar.2016.06.001
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