Challenges and Conundrums in Cannabinoid-Based Treatments for Epilepsy Syndromes and Associated Neurobehavioral Comorbidities

Epilepsy is more than spontaneous recurrent seizures and should be considered a spectrum disorder that can be accompanied by a great diversity of behavioral manifestations. Thus, epilepsy syndromes include not only seizures, but also several comorbid conditions related to behavioral and psychiatric disorders such as depression, anxiety, learning disabilities, attention- deficit hyperactivity disorder and autism. A strong interest in the use of Cannabis products has developed in recent years to treat epilepsy syndromes and associated neurobehavioral comorbidities. The two primary cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) that interact with cannabinoid receptors in body and brain but differ dramatically in their effects. CBD shows a better-defined anticonvulsant profile than THC, having none of the adverse psychoactive effects and abuse liability. Other phytocannabinoids with some evidence of anti-epileptic activity include cannabidivarin and tetrahydrocannabivarin. Although multiple studies have found that these cannabinoids improve seizure control and have benefits on behavior and sleep, unresolved questions and controversy persist. The effects of cannabinoids in neuropsychiatric comorbidities associated to epilepsies is another issue, particularly when a great deal of data have strongly proven the efficacy of cannabidiol, for example, in depression, anxiety, alone. In all cases, it is currently unclear whether the reported medical benefits are related to a direct action of cannabinoids or were mediated by other neurochemical systems or either the synergistic or antagonistic effects with anti-epileptic drugs. Obviously, the situation is more complex when it comes to epilepsy and associated comorbidities. It has been hotly debated, for example, whether isolated or adjunctive cannabinoids are safe and effective for all types of epilepsy syndromes, for patients of all ages and for all administration routes. Also, there is still insufficient data to clarify interactions between the exogenous anti-seizure activity of cannabinoids and the endogenous cannabinoid system in the brain, as well as, the effects associated with long term treatment or its withdrawal. By using multidisciplinary scientific evidences, the current Frontiers Research Topic aims to clarify the relevance of cannabinoids use for the treatment of the epilepsies, associated comorbidities and behavioral aspects of epilepsy syndromes. Experimental designs in the field of the neurosciences, neurobiology, neuropsychology, clinical neurology, neuropsychiatry, neurophysiology, molecular biology, genetics, neuropharmacology, neuroimaging, bioinformatics, computational neuroscience and modeling, are required to shed light on those critical questions in human, animal and in silico models of epilepsy.

This Research Special Topic calls for all types of articles (Original Research, Methods, Reviews, Protocols, etc.) reporting basic, translational experimental or clinical research from any area related to cannabinoids use in seizures, epilepsy syndromes and comorbidities, epilepsy-induced behavioral changes, behavioral epileptic seizures, biological actions of cannabinoids, chemistry and pharmacokinetics of cannabinoids, biology and function of endocannabinoid system in brain and peripheral tissues, as well as, toxicity and drug interactions of cannabinoids conducted in humans, any type of in vivo, in vitro and in silico studies (computational modeling or simulations).