Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity.

Cannabidiol (CBD), a non-euphoric component of cannabis, reduces seizures in multiple forms of pediatric epilepsies, but the mechanism(s) of anti-seizure action remain unclear. In one leading model, CBD acts at glutamatergic axon terminals, blocking the pro-excitatory actions of an endogenous membrane phospholipid, lysophosphatidylinositol (LPI), at the G-protein-coupled receptor GPR55. However, the impact of LPI-GPR55 signaling at inhibitory synapses and in epileptogenesis remains underexplored.

Regulation of seizure-induced MeCP2 Ser421 phosphorylation in the developing brain.

Neonatal seizures disrupt normal synaptic maturation and often lead to later-life epilepsy and cognitive deficits. During early life, the brain exhibits heightened synaptic plasticity, in part due to a developmental overabundance of Ca1.2 L-type voltage gated calcium (Ca) channels (LT-VGCCs) and Ca-permeable AMPARs (CP-AMPARs) lacking GluA2 subunits.

Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol.

Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD.

Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection.

The isolation and identification of the discrete plant cannabinoids in marijuana revived interest in analyzing historical therapeutic claims made for cannabis in clinical case studies and anecdotes. In particular, sources as old as the 11th and 15th centuries claimed efficacy for crude marijuana extracts in the treatment of convulsive disorders, prompting a particularly active area of preclinical research into the therapeutic potential of plant cannabinoids in epilepsy. Since that time, a large body of literature has accumulated describing the effects of several of the >100 individual plant cannabinoids in preclinical models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection.

Cannabinoids and Epilepsy.

Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabis-based antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro- and anticonvulsive effects of cannabinoids [e.

Lestaurtinib (CEP-701) attenuates "second hit" kainic acid-induced seizures following early life hypoxic seizures.

Tropomyosin-related kinase receptor B (TrkB) activation has been implicated in epileptogenesis. We investigated hippocampal levels of phosphorylated TrkB (p-TrkB) and potential antiepileptogenic actions of the tyrosine kinase inhibitor, lestaurtinib (CEP-701) in postnatal day 10 (P10) rat pups following hypoxic seizures (HS). Hippocampal expression of p-TrkB over total TrkB protein levels were assessed by immunoblot at 6, 12, or 24 h post-HS, and revealed a statistically significant and transient 1.