Background Patients with Lennox-Gastaut syndrome, a rare, severe form of epileptic encephalopathy, are frequently treatment resistant to available medications. No controlled studies have investigated the use of cannabidiol for patients with seizures associated with Lennox-Gastaut syndrome. We therefore assessed the efficacy and safety of cannabidiol as an add-on anticonvulsant therapy in this population of patients. Methods In this randomised, double-blind, placebo-controlled trial done at 24 clinical sites in the USA, the Netherlands, and Poland, we investigated the efficacy of cannabidiol as add-on therapy for drop seizures in patients with treatment-resistant Lennox-Gastaut syndrome. Eligible patients (aged 2–55 years) had Lennox-Gastaut syndrome, including a history of...

Abnormal and sometimes severe behavioral and molecular symptoms are usually observed in epileptic humans and animals. To address this issue, we examined the behavioral and molecular aspects of seizure evoked by pilocarpine. Autophagy can promote both cell survival and death, but there are controversial reports about the neuroprotective or neurodegenerative effects of autophagy in seizure. Cannabidiol has anticonvulsant properties in some animal models when used as a pretreatment. In this study, we investigated alteration of seizure scores, autophagy pathway proteins, and antioxidant status in hippocampal cells during the chronic phase of pilocarpine-induced epilepsy after treatment with cannabidiol. Cannabidiol (100 ng, intracerebroventricular injection) delayed the...

To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regard to its relevance to epilepsy and other selected neuropsychiatric disorders. We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology, and data from studies with animal models and human subjects. Cannabis has been used to treat disease since ancient times. D9 -Tetrahydrocannabinol (D9 -THC) is the major psychoactive ingredient and CBD is the major nonpsychoactive ingredient in cannabis. Cannabis and D9 -THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. The psychotropic...

To date, anticonvulsant effects of the plant cannabinoid, cannabidivarin (CBDV), have been reported in several animal models of seizure. However, these behaviourally observed anticonvulsant effects have not been confirmed at the molecular level. To examine changes to epilepsy-related gene expression following chemical convulsant treatment and their subsequent control by phytocannabinoid administration, we behaviourally evaluated effects of CBDV (400 mg/kg, p.o.) on acute, pentylenetetrazole (PTZ: 95 mg/kg, i.p.)-induced seizures, quantified expression levels of several epilepsy-related genes (Fos, Casp 3, Ccl3, Ccl4, Npy, Arc, Penk, Camk2a, Bdnf and Egr1) by qPCR using hippocampal, neocortical and prefrontal cortical tissue samples before examining correlations between expression changes and...

BACKGROUND AND PURPOSE Phytocannabinoids in Cannabis sativa have diverse pharmacological targets extending beyond cannabinoid receptors and several exert notable anticonvulsant effects. For the first time, we investigated the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models. EXPERIMENTAL APPROACH The effect of CBDV (1–100 mM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4-aminopyridine (4-AP) application or Mg2+ -free conditions was assessed by in vitro multi-electrode array recordings. Additionally, the anticonvulsant profile of CBDV (50–200 mg·kg-1 ) in vivo was investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in...

BACKGROUND AND PURPOSE Epilepsy is the most prevalent neurological disease and is characterized by recurrent seizures. Here, we investigate (i) the anticonvulsant profiles of cannabis-derived botanical drug substances (BDSs) rich in cannabidivarin (CBDV) and containing cannabidiol (CBD) in acute in vivo seizure models and (ii) the binding of CBDV BDSs and their components at cannabinoid CB1 receptors. EXPERIMENTAL APPROACH The anticonvulsant profiles of two CBDV BDSs (50–422 mg·kg−1 ) were evaluated in three animal models of acute seizure. Purified CBDV and CBD were also evaluated in an isobolographic study to evaluate potential pharmacological interactions. CBDV BDS effects on motor function were also investigated using...

Abstract Public interest in the use of “medical marijuana” for the treatment of childhood epilepsy has burgeoned in the last few years. This has occurred in parallel with a growing interest in “medical marijuana” in general. Physicians and pediatricians must balance their patients’ desire for immediate access to these products with the tenets of evidence-based medicine. This review discusses the biochemistry of cannabis products (the phytocannabinoids) setting this in the context of the endogenous endocannabinoid system. The differing and potentially modulating effects of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are reviewed. The evidence-base supporting or not the use of cannabis products for the treatment of neurological...

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...