Antipsychotic Drug Risperidone Protected Against Synthetic Cannabinoid Convulsions in Female Mice | Research

The takeaway

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.

Emergency physicians, toxicologists, and synthetic cannabinoid researchers

CB1 antagonist rimonabant worked as both prevention and rescue treatment

What the researchers 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.

Why it 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 numbers in context

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 the study worked

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.

What this study cannot 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.

How to read the evidence

Well-controlled preclinical study with dose-response and sex comparisons, but animal findings need human validation.

When this study was published

2024 study

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.

Questions still open

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?

Common 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.

Read the original research

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

View on PubMed ↗Publisher’s paper ↗

Citation

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