Cannabidiol (CBD) and cognition in epilepsy

Anecdotal reports of the benefits of cannabis and its components in the treatment of epilepsy have been reported for millennia. However, only recently randomized controlled trial data in support of cannabidiol (CBD) became available resulting in its FDA approval for the treatment of seizures and epilepsy. One of the most common and debilitating comorbidities of epilepsy is cognitive impairment. This impairment has a multifactorial etiology including network dysfunction due to seizures, negative cognitive side effects from anti-seizure medications (ASMs), and mood disturbances. Knowing the effects of a particular ASM (either positive or negative) is vital for providers to counsel patients on expected side effects, and may result in choosing a particular regimen over the other if the patient already suffers from significant cognitive deficits. Unlike most other ASMs and other well-studied cannabinoids such as Δ9-tetrahydrocannabinol, CBD has been shown to have additional mechanisms of action (MOA) that result in neuroprotective, anti-inflammatory, anti-oxidant, and neurogenesis effects. These additional MOAs suggest that the use of CBD could lead to other actions including positive effects on cognition that may be independent of seizure control. This targeted review discusses the currently available data on CBD’s effects on cognition in epilepsy. First, we review the proposed mechanisms by which CBD could exert effects on cognition. Then, we present the pre-clinical/animal data investigating cognitive effects of CBD in seizure/epilepsy models. Finally, we discuss the available human data, including the studies in people with epilepsy that included cognitive evaluations pre- and on-CBD, and studies investigating if CBD has any effects on brain structure or function in areas pertinent to memory and cognitive functions.