🎗️New Synthetic “CBD” Combats Seizures Without Causing Sedation

What if it were possible to control seizures without sedating the brain? Scientists created a synthetic molecule similar to CBD that protected mice against different types of seizures and did not cause significant sedation. In animals with genetic epilepsy, the treatment also corrected changes in the connections between neurons.

Some developmental epileptic syndromes begin in childhood and can cause frequent, difficult-to-control seizures. The available medications can help many patients, but some cause drowsiness and other unwanted effects, in addition to losing part of their effect with prolonged use.

Cannabidiol, known as CBD, is already used to treat some specific forms of epilepsy. Now, researchers have created a synthetic molecule similar to CBD in the laboratory, but with small modifications, and discovered that it managed to protect mice against seizures without leaving them sedated.

To find the best molecule, scientists produced several versions similar to CBD, mainly modifying the size of one part of the molecule. The goal was to discover whether these small changes could alter their effects on the brain. 

The compounds were produced from carvone, a substance found in caraway, rather than simply being extracted from cannabis. The researchers then administered the various molecules to mice and monitored their brain activity using electroencephalography, a method that records the brain's electrical waves.

This initial stage made it possible to identify which compounds showed the most interesting effects. One of them, dubbed (+)-CBD-oct by the researchers, was selected for subsequent testing. Then came the key question: could this molecule actually prevent seizures?

To find out, the researchers used two different mouse models of epilepsy. In one, they induced seizures using a substance called kainic acid, which sharply increases neuronal activity. In the other, they used mice with a genetic alteration linked to a form of developmental epilepsy.

Caraway Seeds

The animals received the compound before the tests and were monitored during the seizures. The treatment increased resistance to seizures and, in the kainic acid-induced model, also increased the animals' survival.

But there was another important question: were the animals simply becoming sedated?

To find out, the researchers conducted a behavioral test known as the open-field test. Mice are placed in an enclosure, and their movements are observed. If a substance causes strong sedation, the animals typically become much less active.

(+)-CBD-oct did not produce this significant effect. This suggests that the reduction in seizures did not occur simply because the animals became drowsy or experienced excessive brain slowing.

Scientists also wanted to know if the treatment could influence brain development. To this end, they administered the compound orally over five days to very young mice. They then analyzed the animals' neurons under a microscope, observing small structures known as dendritic spines, which play a role in the connections between nerve cells.

Animals with the genetic alteration displayed these structures differently than normal. Following treatment, this abnormality was normalized. This same effect was not observed in animals that did not carry the genetic alteration.

The results are promising, but they are still far from representing a new treatment for humans. The study was conducted on mice; further research is needed to determine if the molecule is safe for humans, what the appropriate dosage would be, and whether it could effectively control various types of epilepsy.

Nevertheless, the study demonstrates that minor modifications to molecules similar to CBD can produce different effects on the brain. In the future, this strategy could help researchers develop medications capable of controlling seizures without causing significant sedation.

READ MORE: 

Carvone derived cannabidiol enantiomers as novel anticonvulsants

Rochelle M. Hines, April Contreras, Adriana Carrillo, Alexandra Paton, Antonio J. Tenorio, William A. Maio, and  Dustin J. Hines

Neuropsychopharmacol. 50, 1970-1981 (2025)

https://doi.org/10.1038/s41386-025-02220-1

Abstract: 

Developmental epilepsy syndromes are characterized by recurrent seizures and developmental delays. Current anticonvulsants target γ-aminobutyric acid type A receptor signaling to decrease neuronal excitability, however, there are adverse effects for the developing brain, and many patients are refractory. The major non-psychotropic phytocannabinoid cannabidiol (CBD) has emerged as an anti-seizure medication effective in select developmental epilepsy syndromes, but its overall applicability in treating seizure disorders is limited. In the present study, we characterize a small library of non-Cannabis carvone derived CBD (+) enantiomers, with the larger goal of identifying novel therapeutics for developmental epilepsy syndromes. EEG based structure activity relationship assessment supports that elongated alkyl chains increase the potency of the congeners, with (+)-CBD-oct displaying effects on both δ and θ frequency bands. Pre-treatment with (+)-CBD-oct promotes seizure resilience in both wildtype mice and the Gabra2-1 model of developmental epilepsy by influencing seizure characteristics, and reduces mortality. 5 days of (+)-CBD-oct oral gavage in wildtype and Gabra2-1 mice during postnatal development normalizes the aberrant dendritic spine phenotype of Gabra2-1 mice. These findings advance the development of novel anticonvulsants by validating an influence of alkyl chain length of synthetic CBD congeners.