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  • Epilepsy
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Antiseizure Effects of Cannabidiol Leading to Increased Peroxisome Proliferator-Activated Receptor Gamma Levels in the Hippocampal CA3 Subfield of Epileptic Rats

Abstract We evaluated the effects of cannabidiol (CBD) on seizures and peroxisome proliferator-activated receptor gamma (PPARγ) levels in an animal model of temporal lobe epilepsy (TLE). Adult male Sprague-Dawley rats were continuously monitored by video-electrocorticography up to 10 weeks after an intraperitoneal kainic acid (15 mg/kg) injection. Sixty-seven days after the induction of status epilepticus and the appearance of spontaneous recurrent seizures in all rats, CBD was dissolved in medium-chain triglyceride (MCT) oil and administered subcutaneously at 120 mg/kg (n = 10) or 12 mg/kg (n = 10), twice a day for three days. Similarly, the vehicle was administered to ten epileptic rats. Brain levels of...
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Biochemical aspects and therapeutic mechanisms of cannabidiol in epilepsy

Please use this link to access publication Abstract Epilepsy is a chronic neurological disease characterized by recurrent epileptic seizures. Studies have shown the complexity of epileptogenesis and ictogenesis, in which immunological processes and epigenetic and structural changes in neuronal tissues have been identified as triggering epilepsy. Cannabidiol (CBD) is a major active component of the Cannabis plant and the source of CBD-enriched products for the treatment of epilepsy and associated diseases. In this review, we provide an up-to-date discussion on cellular and molecular mechanisms triggered during epilepsy crises, and the phytochemical characteristics of CBD that make it an attractive candidate for controlling rare syndromes, with excellent therapeutic properties. We also...
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An Open Retrospective Study of a Standardized Cannabidiol Based-Oil in Treatment-Resistant Epilepsy

Please use this link to access this publication Abstract Introduction: Cannabidiol (CBD) has antiseizure properties but no psychoactive effects. Randomized controlled trials of an oral, pharmaceutical formulation of highly purified CBD are promising; however, data regarding other formulations are sparse and anecdotal. We evaluated the effectiveness of add-on therapy with a standardized CBD-based oil in treatment-resistant epilepsy (TRE) patients. Materials and Methods: An open retrospective study was carried out on patients with refractory epilepsy of different etiology. We reviewed clinical data from medical charts and caregiver's information. Participants received add-on with 24% CBD-based oil, sublingually administered, at the starting dose of 5–10 mg/[kg·day] up to the maximum...
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Cannabidiol Increases Seizure Resistance and Improves Behavior in an Scn8a Mouse Model

Abstract Voltage-gated sodium channel genes are an important family of human epilepsy genes. De novo missense mutations in SCN8A (encoding Nav1.6) are associated with a spectrum of clinical presentation, including multiple seizure types, movement disorders, intellectual disability, and behavioral abnormalities such as autism. Patients with SCN8A mutations are often treated with multiple antiepileptic drugs, the most common being sodium channel blockers. Cannabidiol (CBD) has been included as a component of treatment regimens for some SCN8A patients; however, to date, there are no clinical trials that have evaluated the therapeutic potential of CBD in patients with SCN8A mutations. In the current manuscript, we demonstrated a dose-dependent increase in seizure resistance following CBD treatment in mice...
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Anticonvulsant Action and Long-Term Effects of Chronic Cannabidiol Treatment in the Rat Pentylenetetrazole-Kindling Model of Epilepsy

Abstract Cannabidiol (CBD) showed anticonvulsant action in several preclinical models and is currently approved by regulatory agencies to treat childhood epilepsy syndromes. However, CBD treatment has limited benefits, and its long-term effects on cognition are not fully understood yet. This study aimed to examine the impact of long-term CBD treatment in the pentylenetetrazole (PTZ)-kindling model of epilepsy. Adult male Wistar rats (N = 24) received PTZ (35 mg/kg intraperitoneally) every other day until two consecutive generalized seizures occurred. CBD (60 mg/kg body weight) was administered daily by the oral route until the kindled state was achieved (n = 12). To confirm that the formulation and administration...
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Prophylactic Administration of Cannabidiol Reduces Microglial Inflammatory Response to Kainate-Induced Seizures and Neurogenesis

Please use this link to access this publication. Abstract Microglia, the dynamic innate immune cells of the central nervous system, become activated in epilepsy. The process of microglial activation in epilepsy results in the creation of an inflammatory environment around the site of seizure onset, which contributes to the epileptogenic process and epilepsy progression. Cannabidiol (CBD) has been effective for use as an adjunctive treatment for two severe pediatric seizure disorders. Newly recognized as an Food and Drug Administration (FDA)-approved drug treatment in epilepsy, it has gained in popularity primarily for pain management. Although CBD is readily available in stores and online retailers, its...
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Effects of chronic cannabidiol in a mouse model of naturally occurring neuroinflammation, neurodegeneration, and spontaneous seizures

Abstract Cannabidiol (CBD) has gained attention as a therapeutic agent and is purported to have immunomodulatory, neuroprotective, and anti-seizure effects. Here, we determined the effects of chronic CBD administration in a mouse model of CLN1 disease (Cln1−/−) that simultaneously exhibits neuroinflammation, neurodegeneration, and spontaneous seizures. Proteomic analysis showed that putative CBD receptors are expressed at similar levels in the brains of Cln1−/− mice compared to normal animals. Cln1−/− mice received an oral dose (100 mg/kg/day) of CBD for six months and were evaluated for changes in pathological markers of disease and seizures. Chronic cannabidiol administration was well-tolerated, high levels of CBD were detected in the brain, and markers of...
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Neuroprotection of cannabidiol in epileptic rats: Gut microbiome and metabolome sequencing

Abstract Aims: Epilepsy is a neurological disease occurring worldwide. Alterations in the gut microbial composition may be involved in the development of Epilepsy. The study aimed to investigate the effects of cannabidiol (CBD) on gut microbiota and the metabolic profile of epileptic rats. Materials and methods and results: A temporal lobe epilepsy rat model was established using Li-pilocarpine. CBD increased the incubation period and reduced the epileptic state in rats. Compared to epileptic rats, the M1/M2 ratio of microglia in the CBD group was significantly decreased. The expression of IL-1β, IL-6, and TNF-α in the CBD group decreased, while IL-10, IL-4, and TGF-β1 increased. 16S rDNA...
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Variability in Serum Concentrations and Clinical Response in Artisanal Versus Pharmaceutical Cannabidiol Treatment of Pediatric Pharmacoresistant Epilepsy

Abstract OBJECTIVE We hypothesized that serum cannabidiol (CBD) concentrations would be higher in patients taking pharmaceutical- versus artisanal-CBD oil, and higher serum CBD concentrations would correlate with increased side effects and decreased seizure frequency. METHODS This was a retrospective chart review. We included patients with pharmacoresistant epilepsy, treated with artisanal-CBD or pharmaceutical-CBD (Epidiolex), and with quantitative serum CBD concentrations. We tracked epilepsy diagnosis, artisanal-CBD dosage, pharmaceutical-CBD dose, serum CBD concentration, clobazam concentration, N-desmethylclobazam concentration, seizure history (frequency of motor seizures), response to medication (percentage reduction in motor seizures), and side effects. RESULTS Forty-two patients met inclusion criteria. Mean serum CBD concentration was 51.1 ng/mL...
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A Pilot Study on the Use of Low Doses of CBD to Control Seizures in Rare and Severe Forms of Drug-Resistant Epilepsy

Abstract Due to its anticonvulsant properties, cannabidiol can be supportive as an adjuvant therapy in the management of drug resistant epilepsy. This retrospective observational study evaluates the intensity and frequency of the seizures of patients with drug-resistant epilepsy that have been treated with antiepileptic medication associated with CBD in low doses for at least 12 months. Thirty-four patients were included in the study. The most frequent diagnosis of epilepsy was focal symptomatic epilepsy and Lennox–Gastaut syndrome (35.2%). During the follow-up, there was a statistically significant decrease in the seizure frequency (t student p < 0.001). A high proportion of patients, 16, concluded the study with a...
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