Antipsychotic Drug Risperidone Protected Against Synthetic Cannabinoid Convulsions in Female Mice
The synthetic cannabinoid AMB-FUBINACA caused hypothermia and convulsions in mice that were CB1-receptor dependent, and co-exposure with the party drug pFPP worsened hypothermia, while the antipsychotic risperidone protected female mice from convulsions.
Quick Facts
What This Study Found
AMB-FUBINACA induced dose-dependent hypothermia and convulsions that were reversible with the CB1 antagonist rimonabant, confirming CB1 dependence. Combining AMB-FUBINACA with pFPP (a party pill drug) significantly worsened hypothermia. Risperidone pre-treatment also potentiated hypothermia but provided significant protection from convulsions in female mice. Rimonabant was effective as both a pre- and post-treatment for AMB-FUBINACA toxicity.
Key Numbers
AMB-FUBINACA: 3 and 6 mg/kg. pFPP: 10 and 20 mg/kg. Risperidone: 0.5 mg/kg. Rimonabant: 3 mg/kg. Rimonabant effective as both pre- and post-treatment. Risperidone protected from convulsions in females only.
How They Did This
Male and female C57BL/6 mice received single IP doses of AMB-FUBINACA (3 or 6 mg/kg) alone or combined with pFPP (10 or 20 mg/kg) or risperidone (0.5 mg/kg). Rimonabant (3 mg/kg) was tested as both pre- and post-treatment. Hypothermia and convulsions were recorded.
Why This Research Matters
Synthetic cannabinoids like AMB-FUBINACA have caused numerous fatalities. This study identifies drug interactions that worsen toxicity (pFPP) and potential rescue strategies (rimonabant), while the sex-specific protective effect of risperidone against convulsions has clinical implications.
The Bigger Picture
Synthetic cannabinoid users often combine multiple drugs, and some may be on antipsychotic medications. Understanding how these interactions affect toxicity is essential for emergency medicine and overdose treatment.
What This Study Doesn't Tell Us
Mouse study; doses and drug interactions may differ in humans. Sex-specific effects of risperidone on convulsions were unexpected and need confirmation. Only one synthetic cannabinoid tested. IP administration does not reflect typical human routes.
Questions This Raises
- ?Why did risperidone protect only female mice from convulsions?
- ?Could rimonabant be developed as an emergency antidote for synthetic cannabinoid overdose?
- ?How do other common co-used drugs interact with synthetic cannabinoids?
Trust & Context
- Key Stat:
- CB1 antagonist rimonabant worked as both prevention and rescue treatment
- Evidence Grade:
- Well-controlled preclinical study with dose-response and sex comparisons, but animal findings need human validation.
- Study Age:
- 2024 study
- Original Title:
- The impact of piperazine and antipsychotic co-exposures and CB1 blockade on the effects elicited by AMB-FUBINACA, a synthetic cannabinoid, in mice.
- Published In:
- European journal of pharmacology, 979, 176844 (2024)
- Authors:
- Thomsen, Lucy R(2), Glass, Michelle(9), Rosengren, Rhonda J(3)
- Database ID:
- RTHC-05761
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
Is there an antidote for synthetic cannabinoid overdose?
In mice, the CB1 receptor antagonist rimonabant reversed both hypothermia and convulsions from the synthetic cannabinoid AMB-FUBINACA, even when given after exposure. This has not been tested in humans.
Does mixing other drugs with synthetic cannabinoids make them more dangerous?
Yes. In this study, combining AMB-FUBINACA with the party drug pFPP significantly worsened hypothermia. Drug combinations create unpredictable and potentially fatal interactions.
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Cite This Study
https://rethinkthc.com/research/RTHC-05761APA
Thomsen, Lucy R; Glass, Michelle; Rosengren, Rhonda J. (2024). The impact of piperazine and antipsychotic co-exposures and CB1 blockade on the effects elicited by AMB-FUBINACA, a synthetic cannabinoid, in mice.. European journal of pharmacology, 979, 176844. https://doi.org/10.1016/j.ejphar.2024.176844
MLA
Thomsen, Lucy R, et al. "The impact of piperazine and antipsychotic co-exposures and CB1 blockade on the effects elicited by AMB-FUBINACA, a synthetic cannabinoid, in mice.." European journal of pharmacology, 2024. https://doi.org/10.1016/j.ejphar.2024.176844
RethinkTHC
RethinkTHC Research Database. "The impact of piperazine and antipsychotic co-exposures and ..." RTHC-05761. Retrieved from https://rethinkthc.com/research/thomsen-2024-the-impact-of-piperazine
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.