“Despite the constant development of new antiepileptic drugs (AEDs), more than 30% of patients develop refractory epilepsy (RE) characterized by a multidrug-resistant (MDR) phenotype. The “transporters hypothesis” indicates that the mechanism of this MDR phenotype is the overexpression of ABC transporters such as P-glycoprotein (P-gp) in the neurovascular unit cells, limiting access of the AEDs to the brain.
Recent clinical trials and basic studies have shown encouraging results for the use of cannabinoids in RE, although its mechanisms of action are still not fully understood. Here, we have employed astrocytes and vascular endothelial cell cultures subjected to hypoxia, to test the effect of cannabidiol (CBD) on the P-gp-dependent Rhodamine-123 (Rho-123) efflux.
Results show that during hypoxia, intracellular Rho-123 accumulation after CBD treatment is similar to that induced by the P-gp inhibitor Tariquidar (Tq). Noteworthy, this inhibition is like that registered in non-hypoxia conditions. Additionally, docking studies predicted that CBD could behave as a P-gp substrate by the interaction with several residues in the α-helix of the P-gp transmembrane domain.
Overall, these findings suggest a direct effect of CBD on the Rho-123 P-gp-dependent efflux activity, which might explain why the CBD add-on treatment regimen in RE patients results in a significant reduction in seizure frequency.”
https://www.ncbi.nlm.nih.gov/pubmed/32256321
“Interestingly, for several thousand years, humanity has given medicinal use to Cannabis sativa (Marijuana), even for the treatment of epileptic patients. Our results indicate that, in addition to the various effects previously described by CBD, this drug can also inhibit the active efflux of Rho-123, a known P-gp substrate, in two types of cells of the NVU, in a similar (though less potent) manner to TQ. Consistently, our in silico study indicates that CBD may bind the transmembrane domain of P-gp, possibly acting as a competitive inhibitor. CBD could thus be used as an adjuvant therapy to reverse the MDR phenotype as observed in patients with RE, which could explain its recent approval as an add-on therapy to treat severe refractory childhood epilepsies.”
https://www.frontiersin.org/articles/10.3389/fnbeh.2020.00032/full
“Many epilepsy patients are refractory to conventional antiepileptic drugs.
“Cannabis has been considered as a therapeutic strategy to control intractable epilepsy.
“The growing interest in cannabidiol (CBD), specifically a pure form of CBD, as a treatment for epilepsy, among other conditions, is reflected in recent changes in legislation in some countries.
“Highly purified 
“In recent years, cannabis has been gaining increasing interest in both the medical research and clinical fields, with regard to its therapeutic effects in various disorders. One of the major fields of interest is its role as an anticonvulsant for refractory epilepsy, especially in the pediatric population. This paper presents and discusses the current accumulated knowledge regarding artisanal cannabis and Epidiolex®, a United States Food and Drug Administration (FDA)-approved pure 
“Epilepsy is a neurological disorder characterized by the presence of seizures and neuropsychiatric comorbidities. Despite the number of antiepileptic drugs, one-third of patients did not have their seizures under control, leading to pharmacoresistance epilepsy.
“Cannabis sativa L. is an ancient medicinal plant wherefrom over 120 cannabinoids are extracted. In the past two decades, there has been increasing interest in the therapeutic potential of cannabis-based treatments for neurological disorders such as epilepsy, and there is now evidence for the medical use of cannabis and its effectiveness for a wide range of diseases.