Neural connections regenerating in a brain, symbolizing epilepsy treatment and neurogenesis.

Epilepsy Breakthrough: Can a Unique Drug Combo Boost Brain Regeneration?

Nico Varela in Health & Wellness December 2025 • 4 min read.

"New research explores how combining levetiracetam with ACEA could revolutionize treatment by stimulating neurogenesis in mouse brains, offering hope for enhanced cognitive function."

Epilepsy, a chronic neurological disorder characterized by recurrent seizures, affects millions worldwide. While various antiepileptic drugs (AEDs) are available, many patients continue to experience seizures, and the long-term effects of these medications on brain health remain a significant concern. Traditional AEDs primarily focus on controlling seizures, but emerging research is exploring innovative approaches that promote brain regeneration and neuroprotection.

Neurogenesis, the process of generating new neurons in the brain, plays a crucial role in learning, memory, and overall cognitive function. Studies have shown that epilepsy and certain AEDs can disrupt neurogenesis, potentially leading to cognitive decline and other neurological complications. Therefore, strategies that enhance neurogenesis could offer significant benefits for individuals with epilepsy.

Recent research has focused on the potential of combining existing AEDs with compounds that stimulate neurogenesis. One promising approach involves combining levetiracetam (LEV), a commonly prescribed AED, with arachidonyl-2'-chloroethylamide (ACEA), a highly selective cannabinoid CB1 receptor agonist. This combination aims to control seizures while simultaneously promoting brain regeneration, offering a dual-action treatment strategy.

Levetiracetam and ACEA: A Synergistic Approach to Epilepsy Treatment?

Neural connections regenerating in a brain, symbolizing epilepsy treatment and neurogenesis.

A recent study published in Neuroscience Letters investigated the effects of combining levetiracetam (LEV) with ACEA on neurogenesis in mouse brains. The researchers hypothesized that this combination could enhance neurogenesis, counteracting the potential negative effects of LEV alone. The study aimed to evaluate the impact of this drug combination on proliferating neural precursor cells and hippocampal neurogenesis.

The study involved a series of experiments on male CB57/BL mice, which were administered LEV, ACEA, and phenylmethylsulfonyl fluoride (PMSF), a compound used to inhibit the breakdown of ACEA. The researchers assessed the effects of these treatments on cell proliferation (using Ki-67 staining) and neurogenesis (using BrDU, NeuN, and GFAP staining).

The study's key findings include:

ACEA+PMSF and ACEA+PMSF+LEV significantly increased the total number of Ki-67 positive cells, indicating enhanced cell proliferation compared to the control group.
ACEA, when administered in combination with LEV, had a significant impact on neurogenesis, increasing the total number of newborn neurons compared to the control group.
LEV alone decreased the process of neurogenesis, suggesting a potential negative impact on brain regeneration.

These results suggest that combining LEV with ACEA could offer a synergistic approach to epilepsy treatment, controlling seizures while simultaneously promoting brain regeneration. The increase in Ki-67 positive cells and newborn neurons indicates that this combination may enhance neurogenesis, potentially counteracting the negative effects of LEV alone.

Future Directions and Clinical Implications

While these findings are promising, further research is needed to fully understand the long-term effects of combining LEV with ACEA on brain health and cognitive function. Future studies should investigate the optimal dosages, treatment durations, and potential side effects of this combination. Clinical trials are necessary to determine whether these findings can be translated to human patients with epilepsy. If successful, this approach could revolutionize epilepsy treatment, offering a dual-action strategy that controls seizures while promoting brain regeneration.

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This article is based on research published under:

DOI-LINK: 10.1016/j.neulet.2018.12.016, Alternate LINK

Title: Levetiracetam Combined With Acea, Highly Selective Cannabinoid Cb1 Receptor Agonist Changes Neurogenesis In Mouse Brain

Subject: General Neuroscience

Journal: Neuroscience Letters

Publisher: Elsevier BV

Authors: Mirosław Zagaja, Agnieszka Haratym-Maj, Aleksandra Szewczyk, Radoslaw Rola, Maciej Maj, Jarogniew J. Łuszczki, Marta Andres-Mach

Published: 2019-03-01

Everything You Need To Know

What is epilepsy, and why is it a significant concern in the context of this research?

Epilepsy is a chronic neurological disorder characterized by recurrent seizures. It affects millions globally. The article highlights the need for treatments that not only control seizures but also address potential long-term effects on brain health. Traditional antiepileptic drugs (AEDs) primarily manage seizures, but there is growing interest in approaches that promote brain regeneration and neuroprotection to address the disorder more comprehensively.

What is neurogenesis, and why is it relevant to epilepsy and its treatment?

Neurogenesis is the process of generating new neurons in the brain, essential for learning, memory, and overall cognitive function. Disruptions to neurogenesis, caused by conditions like epilepsy or certain antiepileptic drugs (AEDs), can lead to cognitive decline and other neurological complications. Therefore, strategies to enhance neurogenesis are crucial for improving outcomes for individuals with epilepsy, as they address the potential negative impact on brain regeneration.

What is the novel drug combination being studied to treat epilepsy, and what are the components?

The article discusses a study that combined levetiracetam (LEV), a commonly prescribed AED, with arachidonyl-2'-chloroethylamide (ACEA), a cannabinoid CB1 receptor agonist. This combination aims to provide a dual-action approach: controlling seizures while simultaneously stimulating brain regeneration. The use of phenylmethylsulfonyl fluoride (PMSF) was also included in the study to inhibit the breakdown of ACEA, enhancing its effectiveness.

What were the key findings of the study regarding levetiracetam and ACEA?

The study found that combining levetiracetam (LEV) with ACEA increased the number of Ki-67 positive cells, indicating enhanced cell proliferation, and also increased the number of newborn neurons. LEV alone showed a potential negative impact on neurogenesis. These results suggest a synergistic effect where ACEA counteracts the potential negative effects of LEV on brain regeneration, which could be crucial for long-term brain health in epilepsy treatment.

What are the potential implications of these findings, and what future steps are needed?

The findings suggest that combining levetiracetam (LEV) with ACEA could revolutionize epilepsy treatment by providing a dual-action strategy: controlling seizures and promoting brain regeneration. However, further research is needed to understand the long-term effects, optimal dosages, and potential side effects. Clinical trials are necessary to determine if these findings can be translated to human patients. If successful, this approach could significantly improve the quality of life for individuals with epilepsy by addressing both seizure control and brain health.