CBD Studies on Epilepsy and Cognition Indicate No Negative Effects, Review Finds

Cannabidiol (CBD) may have the potential to improve or stabilize cognition in epilepsy, according to a review of recent studies published in Epilepsy & Behavior.¹

One of the most well-researched benefits of CBD has been regarding patients with epilepsy. In fact, in 2018, the FDA approved the first drug to contain a purified substance derived from cannabis (Epidiolex).² Studies have found that CBD can significantly reduce seizures in people with treatment-refractory epilepsy, and is generally well-tolerated by patients.¹

However, a critical aspect of anti-seizure medication that remains understudied is its effect on cognition. “This is because of the high incidence of comorbid cognitive deficits in people with epilepsy,” authors noted. At least half of individuals with epilepsy experience cognitive deficits, in many cases caused by anti-seizure medications.

Investigators aimed to determine the positive or negative effects CBD may have on cognition in patients with epilepsy, characterize acute and chronic effects, and examine whether the pure cannabinoid can lead to changes in brain structure or function in relation to cognitive function.

The review first dove into the potential mechanisms of CBD that could be impacting cognition. CBD is unique to many other phytocannabinoids as it displays poor affinity to the endocannabinoid system/cannabinoid receptors and instead utilizes alternative pathways. Study authors discussed how CBD reduces the reuptake of cannabinoids already present in the body, including anandamide and 2-arachidonoylglycerol. Data from previous research has shown that CBD’s neuroprotective and anti-inflammatory effects could create positive effects on cognition. These effects have been studied in Alzheimer disease, but could also demonstrate the same in epilepsy, authors wrote, as CBD has been shown to reduce neuroinflammation and prevent oxidative stress, both of which negatively impact patients with epilepsy.

CBD may also create positive cognitive effects through its effects on neurogenesis and synaptic transmission. CBD is able to increase hippocampal mRNA expression of brain-derived neurotrophic factor, effectively promoting neurogenesis, which is critical for learning and memory. CBD can inhibit reuptake of adenosine at synaptic terminals and modulate brain-derived neurotrophic factor-mediated effects that improves neural transmission and therefore also cognition, according to study authors.

CBD also has the potential to address mood disorders that are common in patients with epilepsy that may lead to negative cognitive effects if not controlled. CBD acts on serotonin receptors to increase synaptic levels of noradrenaline. “Modulating both of these neurotransmitters has been implicated in the management of depression,” the study authors wrote.

Some pre-clinical and animal models analyzing CBD as a treatment for various types of epilepsy have reported behavioral and cognitive results. In one animal study, a group of rats with epilepsy received chronic oral CBD treatment and demonstrated reduced occurrence of reference memory errors. “Those with epilepsy treated with CBD (p<0.05) error rates were significantly lower than the untreated rats with epilepsy,” the study authors explained.

The review identified 2 studies that assessed the effects of highly purified CBD on brain structure in patients with TRE. The first employed voxel-based morphometry to gauge structural changes resulting from 12 weeks of CBD use. Investigators examined gray matter volume and changes in cortical thickness, both of which did not significantly change by the end of the study period. The second study assessed participants with diffusion tensor imaging, where “some significant findings were observed with DSI Studio including increases and decreases in various DTI measures,” the study authors reported.

“As it stands, CBD appears to have the potential to produce improvements or stabilize cognition in epilepsy, and no studies have indicated negative effects,” the authors wrote. “To what extent these effects are dependent on seizure control are not entirely clear, and need further study,” they concluded.

References

1. Gaston TE, Martin RC, Szaflarski JP. Cannabidiol (CBD) and cognition in epilepsy. Epilepsy Behav. 2021;124:108316. doi:10.1016/j.yebeh.2021.108316
2. FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. News release. FDA. June 25, 2018. Accessed November 22, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms