Synthetic cannabinoids produced significantly more seizures than THC in mice
In a direct comparison, synthetic cannabinoids JWH-073 and AM-2201 produced significantly more convulsions than THC in mice, while the endogenous cannabinoid analog methanandamide caused zero seizures despite producing greater hypothermia than THC.
Quick Facts
What This Study Found
JWH-073 and AM-2201 produced significantly more convulsions than THC, HU-210, methanandamide, or CBD. Methanandamide caused no seizures but produced greater hypothermia than THC. Convulsions and hypothermia from several agonists were blocked by a CB1 antagonist but not a CB2 antagonist.
Key Numbers
JWH-073 and AM-2201 produced significantly more convulsions than THC. Methanandamide and CBD produced zero convulsions. Seizure-inducing effects were CB1-mediated (blocked by CB1 but not CB2 antagonist).
How They Did This
Mice received intraperitoneal injections of THC (50 mg/kg), JWH-073 (30 mg/kg), AM-2201 (1 mg/kg), or other cannabinoids at various doses. Convulsions and body temperature changes were quantified. Chronic dosing with tolerance and withdrawal assessment was also performed.
Why This Research Matters
Synthetic cannabinoids found in street products have been linked to seizures and deaths in humans. This study provides controlled evidence that synthetics are genuinely more seizure-prone than THC.
The Bigger Picture
The stark difference between THC and synthetic cannabinoids in seizure potential helps explain the clinical reports of severe adverse events from synthetic products and supports harm reduction messaging that synthetics carry qualitatively different risks.
What This Study Doesn't Tell Us
Mouse model; doses were matched for equivalent analgesic/hypothermic potency rather than recreational potency; limited number of synthetic compounds tested relative to the hundreds on the market.
Questions This Raises
- ?What structural features of synthetic cannabinoids make them more seizure-prone?
- ?Could this information guide risk classification of novel synthetic compounds?
Trust & Context
- Key Stat:
- Synthetic cannabinoids caused significantly more seizures than THC; endogenous cannabinoid analogs caused none
- Evidence Grade:
- Controlled animal study comparing multiple compounds, but limited to a mouse model with a small subset of available synthetic cannabinoids.
- Study Age:
- Published in 2020.
- Original Title:
- Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ9-Tetrahydrocannabinol.
- Published In:
- Cannabis and cannabinoid research, 5(1), 32-41 (2020)
- Authors:
- Breivogel, Chris S(2), Wells, Jacob R, Jonas, Amreen(2), Mistry, Artik H, Gravley, Morgan L, Patel, Rajul M, Whithorn, Brianna E, Brenseke, Bonnie M
- Database ID:
- RTHC-02435
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Why are synthetic cannabinoids more dangerous than THC?
This study found synthetics like JWH-073 and AM-2201 produced significantly more seizures than THC at equivalent potency doses. The effects were CB1-mediated, but the specific structural features that make synthetics more seizure-prone are still being investigated.
Did CBD cause seizures in this study?
No. CBD produced zero convulsions, consistent with its known anticonvulsant properties and its approval as an anti-seizure medication.
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Cite This Study
https://rethinkthc.com/research/RTHC-02435APA
Breivogel, Chris S; Wells, Jacob R; Jonas, Amreen; Mistry, Artik H; Gravley, Morgan L; Patel, Rajul M; Whithorn, Brianna E; Brenseke, Bonnie M. (2020). Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ9-Tetrahydrocannabinol.. Cannabis and cannabinoid research, 5(1), 32-41. https://doi.org/10.1089/can.2019.0003
MLA
Breivogel, Chris S, et al. "Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ9-Tetrahydrocannabinol.." Cannabis and cannabinoid research, 2020. https://doi.org/10.1089/can.2019.0003
RethinkTHC
RethinkTHC Research Database. "Comparison of the Neurotoxic and Seizure-Inducing Effects of..." RTHC-02435. Retrieved from https://rethinkthc.com/research/breivogel-2020-comparison-of-the-neurotoxic
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.