Activating CB2 Receptors Reduced Nausea and Vomiting Without Psychoactive Effects
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- First selective CB2 agonist shown to reduce both vomiting and nausea behavior in animal models.
- Evidence Grade:
- Preliminary evidence from animal models. While the receptor specificity is well demonstrated, human translation has not been tested.
- Study Age:
- Published in 2016. CB2-targeted therapeutics remain an active area of drug development.
- Original Title:
- Cannabinoid 2 (CB2) receptor agonism reduces lithium chloride-induced vomiting in Suncus murinus and nausea-induced conditioned gaping in rats.
- Published In:
- European journal of pharmacology, 786, 94-99 (2016)
- Authors:
- Rock, Erin M(7), Boulet, Nathalie, Limebeer, Cheryl L(11), Mechoulam, Raphael, Parker, Linda A
- Database ID:
- RTHC-01251
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Can you get anti-nausea effects from cannabis without getting high?
This animal study suggests it may be possible by targeting CB2 receptors instead of CB1 receptors. CB2 activation reduced both vomiting and nausea behavior without the psychoactive effects associated with CB1 activation.
What is the difference between CB1 and CB2 receptors?
CB1 receptors are concentrated in the brain and are responsible for the psychoactive effects of THC. CB2 receptors are primarily found in immune cells and peripheral tissues. This study shows CB2 can also reduce nausea, potentially without psychoactive side effects.
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Cite This Study
https://rethinkthc.com/research/RTHC-01251APA
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
MLA
Rock, Erin M, et al. "Cannabinoid 2 (CB2) receptor agonism reduces lithium chloride-induced vomiting in Suncus murinus and nausea-induced conditioned gaping in rats.." European journal of pharmacology, 2016. https://doi.org/10.1016/j.ejphar.2016.06.001
RethinkTHC
RethinkTHC Research Database. "Cannabinoid 2 (CB2) receptor agonism reduces lithium chlorid..." RTHC-01251. Retrieved from https://rethinkthc.com/research/rock-2016-cannabinoid-2-cb2-receptor
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.