Cannabidiol Treatment for Refractory Epilepsies in Pediatrics

Abstract

Cannabis extracts in oil are becoming increasingly available, and, during the last years, there has been growing public and scientific interest about therapeutic properties of these compounds for the treatment of several neurologic diseases, not just epilepsy. The discovered role of the endocannabinoid system in epileptogenesis has provided the basis to investigate the pharmacological use of exogenously produced cannabinoids, to treat epilepsy. Although, physicians show reluctance to recommend Cannabis extracts given the lack of high-quality safety available data, from literature data cannabidiol (CBD) results to be a promising and safe anticonvulsant drug with low side-effect. In particular, according to early studies, CBD can reduce the frequency of seizures and lead to improvements in quality of life in children affected by refractory epilepsy. So, for these reasons, the detailed study of the interactions between CBD and anticonvulsant drugs (AEDs) administered simultaneously in polytherapy, is arousing increasing interest, to clarify and to assess the incidence of adverse effects and the relation between dose escalation and quality of life measures. To date, in pediatric age, CBD efficacy and safety is not supported by well-designed trials and strong scientific evidence are not available. These studies are either retrospective or small-scale observational and only during the last years Class I evidence data for a pure form of CBD have been available, as demonstrated in placebo-controlled RCTs for patients affected by Lennox-Gastaut syndrome and Dravet syndrome. It is necessary to investigate CBD safety, pharmacokinetics and interaction with other AEDs alongside performing double-blinded placebo-controlled trials to obtain conclusive data on its efficacy and safety in the most frequent epilepsies in children, not just in the epileptic encephalopathy. This review was aimed to revise the available data to describe the scientific evidence for CBD in Pediatric Epilepsies.

Epilepsy and cannabidiol - a new perspective for seizures treatment

“…Increasing the availability of CBD as adjunctive medication against severe forms of epilepsy, may in some cases provide significant benefits [6,9,27]. From the available studies in the pediatric population, synthetic cannabidiol oral solution can be considered safe at all doses tested and generally well tolerated in this population [5,10,21].…”

“…In addition, mandatory testing and a basic regulatory framework are also not required to define the area of indication, daily dose, route of administration, maximum recommended daily dose, packaging, shelf life and stability. Much of this inaccuracy stems from the fact that it is not legally regulated whether such products should be regulated as food, supplements or drugs [9,10].…”

Cannabinoid Formulations and Delivery Systems: Current and Future Options to Treat Pain

“…Therapeutic use of cannabis in treatment of infantile spasms has been documented since 1840 but it was only in 2018 that cannabidiol (as Epidiolex marketed medicine) was approved by the FDA and then by the EMA as an add-on antiepileptic drug in children with Dravet syndrome and Lennox–Gastaut syndrome (serious epileptic encephalopathies, generally resistant to treatment). The efficacy of this treatment in reducing seizures frequencies and in improving the quality of life in childhood epilepsy was shown in recent systematic reviews and was summarised by Raucci et al [ 24 ].…”

A Proteomic View of Cellular and Molecular Effects of Cannabis

“…Although the results of this study indicated that CBG at lower concentration compared to CBD showed the same antioxidant effects, CBD showed beneficial effects on neurotransmitter exocytosis, which was not observed in CBG, suggesting that CBD may be a more desirable therapeutic option. Currently, CBD is an FDA-approved treatment option against two rare and severe types of epilepsy including Lennox-Gastaut syndrome (LGS) and Dravet syndrome, in patients two years of age and older [122,123].…”