Synthetic cannabinoid JWH-018 produced nausea-like behavior in rats via CB1 receptors with stress hormone activation
The synthetic cannabinoid JWH-018 (found in "Spice" products) produced conditioned gaping, a nausea indicator, in rats at doses of 1 and 3 mg/kg, an effect reversed by the CB1 antagonist rimonabant and accompanied by elevated stress hormones.
Quick Facts
What This Study Found
JWH-018 at 1 and 3 mg/kg produced conditioned gaping (nausea). The 3 mg/kg effect was reversed by rimonabant, confirming CB1 mediation. JWH-018 elevated serum corticosterone levels, indicating HPA axis activation. This parallels previous findings with high-dose THC.
Key Numbers
JWH-018 at 1 and 3 mg/kg induced conditioned gaping. Rimonabant reversed 3 mg/kg effect. Corticosterone elevated at 3 mg/kg vs. vehicle.
How They Did This
Rats received 3 daily conditioning trials pairing saccharin with JWH-018 (0, 0.1, 1, 3 mg/kg). Rimonabant pretreatment tested for CB1 involvement. Serum corticosterone analyzed after 3 daily JWH-018 injections.
Why This Research Matters
JWH-018 has been found in "Spice" products linked to cannabinoid hyperemesis syndrome. This study provides mechanistic evidence that synthetic cannabinoids produce nausea through CB1-mediated stress response activation.
The Bigger Picture
This supports the hypothesis that cannabinoid hyperemesis syndrome results from CB1-mediated HPA axis dysregulation, explaining why both high-dose THC and synthetic cannabinoids can produce paradoxical nausea.
What This Study Doesn't Tell Us
Animal model; conditioned gaping is a proxy for nausea; JWH-018 doses may not match human recreational exposure; only one synthetic cannabinoid tested.
Questions This Raises
- ?Would other synthetic cannabinoids found in "Spice" produce similar nausea effects?
- ?Could CRH antagonists prevent CHS symptoms in humans?
Trust & Context
- Key Stat:
- JWH-018 nausea was CB1-mediated and accompanied by elevated corticosterone
- Evidence Grade:
- Single animal study with mechanistic detail but limited to one synthetic compound.
- Study Age:
- Published in 2020.
- Original Title:
- Nausea-Induced Conditioned Gaping Reactions in Rats Produced by High-Dose Synthetic Cannabinoid, JWH-018.
- Published In:
- Cannabis and cannabinoid research, 5(4), 298-304 (2020)
- Authors:
- DeVuono, Marieka V(10), Hrelja, Kelly M, Petrie, Gavin N(6), Limebeer, Cheryl L, Rock, Erin M, Hill, Matthew N, Parker, Linda A
- Database ID:
- RTHC-02513
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Why would a cannabinoid cause nausea when cannabis is used to treat nausea?
At low doses, cannabinoids reduce nausea. At high doses or with potent full agonists like JWH-018, they can paradoxically induce nausea through overstimulation of CB1 receptors and activation of the stress response. This is thought to underlie cannabinoid hyperemesis syndrome.
What is the connection to "Spice" products?
JWH-018 is one of the active ingredients found in synthetic cannabis products sold as "Spice." Unlike THC (a partial CB1 agonist), JWH-018 is a full agonist, making it more likely to produce severe effects including nausea and vomiting.
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Cite This Study
https://rethinkthc.com/research/RTHC-02513APA
DeVuono, Marieka V; Hrelja, Kelly M; Petrie, Gavin N; Limebeer, Cheryl L; Rock, Erin M; Hill, Matthew N; Parker, Linda A. (2020). Nausea-Induced Conditioned Gaping Reactions in Rats Produced by High-Dose Synthetic Cannabinoid, JWH-018.. Cannabis and cannabinoid research, 5(4), 298-304. https://doi.org/10.1089/can.2019.0103
MLA
DeVuono, Marieka V, et al. "Nausea-Induced Conditioned Gaping Reactions in Rats Produced by High-Dose Synthetic Cannabinoid, JWH-018.." Cannabis and cannabinoid research, 2020. https://doi.org/10.1089/can.2019.0103
RethinkTHC
RethinkTHC Research Database. "Nausea-Induced Conditioned Gaping Reactions in Rats Produced..." RTHC-02513. Retrieved from https://rethinkthc.com/research/devuono-2020-nauseainduced-conditioned-gaping-reactions
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.