Purpose: To describe the experience of five Israeli pediatric epilepsy clinics treating children and adolescents diagnosed as having intractable epilepsy with a regimen of medical cannabis oil. Methods: A retrospective study describing the effect of cannabidiol (CBD)-enriched medical cannabis on children with epilepsy. The cohort included 74 patients (age range 1–18 years) with intractable epilepsy resistant to >7 antiepileptic drugs. Forty-nine (66%) also failed a ketogenic diet, vagal nerve stimulator implantation, or both. They all started medical cannabis oil treatment between 2–11/2014 and were treated for at least 3 months (average 6 months). The selected formula contained CBD and tetrahydrocannabinol at a ratio of...

In phase 1 of the study, 3 mg/kg daily of cannabidiol (CBD) was given for 30 days to 8 health human volunteers. Another 8 volunteers received the same number of identical capsules containing glucose as placebo in a double-blind setting. Neurological and physical examinations, blood and urine analysis, ECG and EEG were performed at weekly intervals. In phase 2 of the study, 15 patients suffering from secondary generalized epilepsy with temporal focus were randomly divided into two groups. Each patient received, in a double-blind procedure, 200-300 mg daily of CBD or placebo. The drugs were administered for along as 4 1/2 months. Clinical and...

Cannabidiol (CBD) is the most abundant nonpsychoactive cannabinoid in cannabis. Animal studies demonstrate anticonvulsant efficacy in multiple species and models. Anecdotal reports suggest CBD to be effective in children with treatment-resistant epilepsies (TRE), especially Dravet syndrome (DS). We report results of an open label study in children with TRE in an expanded access treatment program conducted in the US under INDs. Efficacy results are reported for all patients who received at least 12 weeks of treatment (n=137). Safety results are reported for all patients who received any treatment (n=213)

Objective: To identify potential pharmacokinetic interactions between the pharmaceutical formulation of cannabidiol (CBD; Epidiolex) and the commonly used antiepileptic drugs (AEDs) through an open-label safety study. Serum levels were monitored to identify interactions between CBD and AEDs. Methods: In 39 adults and 42 children, CBD dose was started at 5 mg/kg/day and increased every 2 weeks by 5 mg/kg/day up to a maximum of 50 mg/kg/day. Serum AED levels were obtained at baseline prior to CBD initiation and at most study visits. AED doses were adjusted if it was determined that a clinical symptom or laboratory result was related to a potential interaction. The...

Abstract Marijuana has been utilized as a medicinal plant to treat a variety of conditions for nearly five millennia. Over the past few years, there has been an unprecedented interest in using cannabis extracts to treat epilepsy, spurred on by a few refractory pediatric cases featured in the media that had an almost miraculous response to cannabidiol-enriched marijuana extracts. This review attempts to answer the most important questions a clinician may have regarding the use of marijuana in epilepsy. First, we review the preclinical and human evidences for the anticonvulsant properties of the different cannabinoids, mainly tetrahydrocannabinol (THC) and cannabidiol (CBD). Then, we explore...

The endocannabinoid system plays a central role in retrograde synaptic communication and may control the spread of activity in an epileptic network. Using the pilocarpine model of temporal lobe epilepsy we examined the expression pattern of the Type 1 cannabinoid receptor (CB1-R) in the hippocampi of CD1 mice at survival times of 2 hours, 1 day, 3 days and 2 months (acute, latent and chronic phases). Based on the behavioral signs of the acute seizures, animals were classified as ‘‘weakly’’ or ‘‘strongly’’ epileptic using the modified Racine scale. Mice of the weak group had mild seizures, whereas seizures in the strong group were frequent...

Severe childhood epilepsies are characterized by frequent seizures, neurodevelopmental delays and impaired quality of life. In these treatment-resistant epilepsies, families often seek alternative treatments. This survey explored the use of cannabidiol-enriched cannabis in children with treatment-resistant epilepsy. The survey was presented to parents belonging to a Facebook group dedicated to sharing information about the use of cannabidiol-enriched cannabis to treat their child’s seizures. Nineteen responses met the inclusion criteria for the study: a diagnosis of epilepsy and current use of cannabidiol-enriched cannabis. Thirteen children had Dravet syndrome, four had Doose syndrome, and one each had Lennox-Gastaut syndrome and idiopathic epilepsy. The average number of...

Intractable epilepsies have an extraordinary impact on cognitive and behavioral function and quality of life, and the treatment of seizures represents a challenge and a unique opportunity. Over the past few years, considerable attention has focused on cannabidiol (CBD), the major nonpsychotropic compound of Cannabis sativa. Basic research studies have provided strong evidence for safety and anticonvulsant properties of CBD. However, the lack of pure, pharmacologically active compounds and legal restrictions have prevented clinical research and confined data on efficacy and safety to anecdotal reports. Pure CBD appears to be an ideal candidate among phytocannabinoids as a therapy for treatment-resistant epilepsy. A first step...