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Study breakdown

THC blocks nausea signals by activating CB1 receptors in the brain

Animal StudyPreliminary evidence
The takeaway

THC and related cannabinoids suppress vomiting triggered by substance P, a key nausea signaling molecule, by activating CB1 receptors.

People interested in the science behind cannabis and nausea relief, particularly those exploring cannabinoid-based options for chemotherapy side effects.

THC dose-dependently blocked vomiting triggered by both substance P and a selective NK1 receptor agonist

What the researchers 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.

Why it 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 numbers in context

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 the study worked

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.

What this study cannot 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.

How to read the evidence

Preliminary: animal model using least shrews with behavioral endpoints only.

When this study was published

Published in 2019.

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.

Questions still open

  • 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?

Common 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.

Read the original research

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

Citation

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

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