THC blocks nausea signals by activating CB1 receptors in the brain
THC and related cannabinoids suppress vomiting triggered by substance P, a key nausea signaling molecule, by activating CB1 receptors.
Quick Facts
What This Study Found
Delta-9-THC, WIN55,212-2, and CP55,940 all dose-dependently suppressed vomiting triggered by substance P and the selective NK1 receptor agonist GR73632 in least shrews. The antiemetic effect was blocked by the CB1 antagonist SR141716A.
Key Numbers
THC suppressed SP-evoked vomiting dose-dependently via both i.p. and s.c. routes. The CB1 antagonist SR141716A fully blocked THC's antiemetic effect. The NK1 antagonist netupitant suppressed vomiting caused by high-dose SR141716A.
How They Did This
Researchers administered varying doses of three cannabinoid receptor agonists to least shrews before inducing vomiting with substance P or GR73632. They tested whether a CB1 antagonist could reverse the antiemetic effects.
Why This Research Matters
Chemotherapy-induced nausea involves both serotonin and substance P pathways. This study shows THC can block the substance P pathway specifically, helping explain why cannabinoids work against nausea that conventional anti-serotonin drugs miss.
The Bigger Picture
Current anti-nausea drugs often target only serotonin receptors, leaving some patients with incomplete relief. Understanding that cannabinoids also block the substance P/NK1 pathway opens a complementary route for managing severe or treatment-resistant nausea.
What This Study Doesn't Tell Us
Conducted in least shrews, not humans. The doses used may not translate directly to human pharmacology. Only acute vomiting was studied, not delayed or anticipatory nausea.
Questions This Raises
- ?Would combining cannabinoids with NK1 antagonists like aprepitant produce stronger anti-nausea effects than either alone?
- ?Do these findings apply to nausea from causes other than chemotherapy?
Trust & Context
- Key Stat:
- THC dose-dependently blocked vomiting triggered by both substance P and a selective NK1 receptor agonist
- Evidence Grade:
- Preliminary: animal model using least shrews with behavioral endpoints only.
- Study Age:
- Published in 2019.
- Original Title:
- Δ9-THC and related cannabinoids suppress substance P- induced neurokinin NK1-receptor-mediated vomiting via activation of cannabinoid CB1 receptor.
- Published In:
- European journal of pharmacology, 865, 172806 (2019)
- Authors:
- Darmani, Nissar A(2), Belkacemi, Louiza, Zhong, Weixia
- Database ID:
- RTHC-01999
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
How does THC stop nausea?
THC activates CB1 receptors in the brain, which suppresses vomiting signals from both serotonin and substance P pathways. This study specifically showed THC blocks the substance P/NK1 receptor pathway.
Why study nausea in shrews?
Least shrews are one of the few small animals that can vomit, making them a standard model for anti-nausea research. Mice and rats cannot vomit.
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Cite This Study
https://rethinkthc.com/research/RTHC-01999APA
Darmani, Nissar A; Belkacemi, Louiza; Zhong, Weixia. (2019). Δ9-THC and related cannabinoids suppress substance P- induced neurokinin NK1-receptor-mediated vomiting via activation of cannabinoid CB1 receptor.. European journal of pharmacology, 865, 172806. https://doi.org/10.1016/j.ejphar.2019.172806
MLA
Darmani, Nissar A, et al. "Δ9-THC and related cannabinoids suppress substance P- induced neurokinin NK1-receptor-mediated vomiting via activation of cannabinoid CB1 receptor.." European journal of pharmacology, 2019. https://doi.org/10.1016/j.ejphar.2019.172806
RethinkTHC
RethinkTHC Research Database. "Δ9-THC and related cannabinoids suppress substance P- induce..." RTHC-01999. Retrieved from https://rethinkthc.com/research/darmani-2019-9thc-and-related-cannabinoids
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.