Activating CB1 receptors raised seizure threshold in mice with brain-infecting parasites | Research

The takeaway

In mice infected with Toxoplasma gondii, which lowers seizure threshold, CB1 receptor activation and endocannabinoid boosting raised the seizure threshold, while CB1 blockade worsened the proconvulsant effect.

Epilepsy researchers, infectious disease specialists, and neuroscientists studying the endocannabinoid system.

CB1 activation raised seizure threshold in infected mice

What the researchers found

The CB1 agonist ACEA, the endocannabinoid-boosting agent JZL184, and the CB2 antagonist AM630 all raised seizure thresholds in both healthy and Toxoplasma-infected mice. Conversely, CB1 antagonist AM251 and CB2 agonist HU308 lowered thresholds.

Why it matters

Toxoplasmosis affects roughly one-third of the global population and is a recognized risk factor for epilepsy. This study identifies the cannabinoid system as a potential therapeutic target for infection-related seizure vulnerability.

The numbers in context

Infected mice had substantially lower seizure thresholds than uninfected mice. JZL184, ACEA, and AM630 each raised thresholds in a dose-dependent manner.

How the study worked

Mice were infected with T. gondii cysts intraperitoneally. During acute and chronic infection, various cannabinoid receptor agonists and antagonists were administered intracerebroventricularly before measuring seizure threshold via pentylenetetrazole infusion.

What this study cannot tell us

Animal study using direct brain injection of drugs, which does not reflect practical human drug delivery. The Toxoplasma model may not fully replicate infection-related epilepsy in humans.

How to read the evidence

Preliminary: animal study with direct brain drug delivery.

When this study was published

Published in 2020 in Microbial Pathogenesis.

The bigger picture

The opposing roles of CB1 (protective) and CB2 (proconvulsant) receptors in infection-related seizures suggest that cannabinoid-based interventions would need careful receptor targeting to be therapeutically useful.

Questions still open

Could cannabinoid-based therapies reduce epilepsy risk in people with chronic toxoplasmosis? Why do CB1 and CB2 receptors have opposing effects on seizure threshold?

Common questions

What is the connection between toxoplasmosis and seizures?

Toxoplasma gondii is a parasite that infects the brain and is known to increase the risk of epilepsy. This study confirmed that infected mice had lower seizure thresholds and showed that the cannabinoid system plays a role in this vulnerability.

Could cannabis help prevent seizures from brain infections?

This study suggests that targeting CB1 receptors could be protective, but the drugs were injected directly into the brain, which is not practical for humans. Whether oral cannabinoids would have similar effects is unknown.

Read the original research

Cannabinoid receptors and the proconvulsant effect of toxoplasmosis in mice.

Microbial pathogenesis, 144, 104204

View on PubMed ↗Publisher’s paper ↗

Citation

Ghanbari, Mohammad-Mahdi; Joneidi, Marzieh; Kiani, Bahere; Babaie, Jalal; Sayyah, Mohammad. (2020). Cannabinoid receptors and the proconvulsant effect of toxoplasmosis in mice.. Microbial pathogenesis, 144, 104204. https://doi.org/10.1016/j.micpath.2020.104204