Synthetic Cannabinoid Convulsions Are Not True Seizures, Mouse Study Suggests | Research

The takeaway

In mice, four synthetic cannabinoids caused visible convulsions that were blocked by a CB1 receptor antagonist but not by the anti-seizure drug diazepam, and EEG recordings confirmed the convulsions were not accompanied by brain seizure activity.

People interested in synthetic cannabinoid toxicity and emergency treatment approaches

4 synthetic cannabinoids tested

What the researchers found

Convulsant doses of AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, and JWH-018 did not produce seizure patterns on EEG despite causing visible convulsions. Rimonabant (CB1 antagonist) blocked the convulsions, but diazepam did not. This suggests the convulsions are CB1-mediated motor events, not epileptic seizures.

Why it matters

Convulsions from synthetic cannabinoids are commonly treated as seizures in emergency rooms. If these are not true seizures, benzodiazepines (the standard seizure treatment) may be ineffective, and different treatment approaches may be needed.

The numbers in context

4 synthetic cannabinoids tested; 10 mg/kg rimonabant blocked convulsions; 10 mg/kg diazepam did not; repeated dosing produced partial tolerance; no cross-tolerance to PTZ-induced convulsions

How the study worked

Mouse study using NIH Swiss mice. Dose-response testing for convulsant effects, with pretreatment experiments using rimonabant, diazepam, and a CYP450 inhibitor. Separate cohort fitted with EEG headmounts to record brain activity during convulsions. Root-mean-square power and spike analysis used to assess seizure-like activity.

What this study cannot tell us

Animal study results may not directly translate to humans. Only male mice were used. Limited number of synthetic cannabinoids tested relative to the hundreds in circulation. EEG recordings in mice have lower spatial resolution than human EEG.

How to read the evidence

Well-designed animal study with multiple compounds and verification methods, but findings need human confirmation

When this study was published

2022 study

The bigger picture

Synthetic cannabinoids remain a public health concern, especially in populations with limited access to regulated cannabis. Understanding that their convulsions differ mechanistically from epileptic seizures could change emergency treatment protocols.

Questions still open

Do these findings hold true in humans experiencing synthetic cannabinoid convulsions? If benzodiazepines are ineffective, what should emergency departments use instead? Do newer-generation synthetic cannabinoids produce the same non-seizure convulsions?

Common questions

Are synthetic cannabinoid convulsions dangerous?

Yes, they can be. This study found they are CB1 receptor-mediated motor events rather than epileptic seizures, which means they may need different treatment than typical seizures.

Why would benzodiazepines not work for these convulsions?

Benzodiazepines work by enhancing GABA signaling to stop seizure activity in the brain. Since these convulsions appear to be driven by CB1 receptor activation rather than abnormal brain electrical activity, the mechanism benzodiazepines target may not be relevant.

Read the original research

Convulsant doses of abused synthetic cannabinoid receptor agonists AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA and JWH-018 do not elicit electroencephalographic (EEG) seizures in male mice.

Psychopharmacology, 239(10), 3237-3248

View on PubMed ↗Publisher’s paper ↗

Citation

Wilson, Catheryn D; Zheng, Fang; Fantegrossi, William E. (2022). Convulsant doses of abused synthetic cannabinoid receptor agonists AB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA and JWH-018 do not elicit electroencephalographic (EEG) seizures in male mice.. Psychopharmacology, 239(10), 3237-3248. https://doi.org/10.1007/s00213-022-06205-6