Category Archives: Epilepsia

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Cannabinoids for epilepsy: What do we know and where do we go?

Category : Epilepsia

Cannabinoids for epilepsy: What do we know and where do we go?

Epilepsia. 2017 Dec 06;:

Authors: Brodie MJ, Ben-Menachem E

Abstract
Over the past decade there has been an increasing interest in using cannabinoids to treat a range of epilepsy syndromes following reports of some remarkable responses in individual patients. The situation is complicated by the fact that these agents do not appear to work via their attachment to endogenous cannabinoid receptors. Their pharmacokinetics are complex, and bioavailability is variable, resulting in difficulty in developing a suitable formulation for oral delivery. Drug interactions also represent another complication in their everyday use. Nevertheless, recent randomized, placebo-controlled trials with cannabidiol support its efficacy in Dravet and Lennox-Gastaut syndromes. Further placebo-controlled studies are underway in adults with focal epilepsy using cannabidivarin. The many unanswered questions in the use of cannabinoids to treat epileptic seizures are briefly summarized in the conclusion.

PMID: 29214639 [PubMed – as supplied by publisher]

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Simple and fast gas-chromatography mass spectrometry assay to assess delta 9-tetrahydrocannabinol and cannabidiol in dogs treated with medical cannabis for canine epilepsy.

Category : Epilepsia

Simple and fast gas-chromatography mass spectrometry assay to assess delta 9-tetrahydrocannabinol and cannabidiol in dogs treated with medical cannabis for canine epilepsy.

Curr Pharm Biotechnol. 2017 Nov 21;:

Authors: Rotolo MC, Graziano S, Pellegrini M, Corlazzoli D, Antinori L, Porcarelli L, Pichini S

Abstract
BACKGROUND: To date, an increasing number of pet owners, especially in the USA, are using cannabis-derived products containing generally delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) to help their animals’ health. Unfortunately, studies on the clinical use of cannabinoids in veterinary medicine are still limited, and the application of analytical methodologies for the determination of cannabinoids in animal (especially dog) biological matrices such as plasma, is still missing.
METHODS: A reliable, fast, accurate, simple gas chromatography-mass spectrometry (GC-MS) method was developed and validated for the quantification of THC and CBD in plasma samples of eight dogs under therapeutic treatment for epilepsy and receiving oral administration of medical cannabis (Bediol).
RESULTS: The method was linear for both the analytes under investigation with coefficients of determination (r2) of at least 0.99. Absolute analytical recovery (mean ± SD) ranged from 80.6 ± 6.2% for THC and 81.7 ± 4.3% for CBD. The matrix effect showed less than 10% analytical suppression due to endogenous substances for both the analytes. The intra-assay and inter-assay precision values ranged from 4.9% to 12.7%, and from 5.2% to 8.7% respectively. The intra-assay and inter-assay accuracy values ranged from 2.3% to 9.6% and from 3.4% to 13.0% respectively. The validated method was successfully applied to real samples; moreover to assess the potential of the method applicability and robustness in future veterinary clinical studies on cannabinoids therapy, we attempted to follow the kinetic of THC and CBD in the plasma of two dogs under therapy at different times after Bediol administration.

PMID: 29173160 [PubMed – as supplied by publisher]

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Cannabidiol as a treatment for epilepsy.

Category : Epilepsia

Cannabidiol as a treatment for epilepsy.

J Neurol. 2017 Nov 09;:

Authors: Pickrell WO, Robertson NP

PMID: 29124331 [PubMed – as supplied by publisher]

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Efficacy and safety of cannabis for treating children with refractory epilepsy.

Category : Epilepsia

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Efficacy and safety of cannabis for treating children with refractory epilepsy.

Nurs Child Young People. 2017 Sep 11;29(7):32-37

Authors: Neale M

Abstract
The aim of this literature review was to examine the evidence base for the safety and efficacy of cannabis in treating children with refractory epilepsy. Clinical and medical databases were searched and four articles were included in the final analysis, which included retrospective reviews and open-label trials with a total sample size of 424. One clinical trial included administration of cannabidiol, the non-psychoactive compound of cannabis, while the other three articles stated that the compound administered to participants contained tetrahydrocannabidiol, the psychoactive constituent of cannabis. Cannabis may reduce seizures in some children and young people with refractory epilepsy, however, its success may be affected by aetiology of the epilepsy or concomitant anti-epileptic drug use, and a therapeutic dose has not been found. Positive side effects were also found including improved sleep, alertness and mood. More research is needed on this subject, including randomised controlled trials. Nurses who are aware of patients and families wishing to trial cannabis for refractory epilepsy should have full and frank discussions.

PMID: 29115760 [PubMed – in process]

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Developmental effects of cannabidiol and Δ9-tetrahydrocannabinol in zebrafish.

Category : Epilepsia

Developmental effects of cannabidiol and Δ9-tetrahydrocannabinol in zebrafish.

Toxicol Sci. 2017 Nov 02;:

Authors: Carty DR, Thornton C, Gledhill J, Willett KL

Abstract
Cannabidiol (CBD) has gained much attention in the past several years for its therapeutic potential in the treatment of drug-resistant epilepsy, such as Dravet Syndrome. While CBD has shown anecdotal efficacy in reducing seizure frequency, little is known regarding the potential adverse side-effects of CBD on physiology, development, organogenesis, or behavior. The goal of this project is to compare the relative morphological, behavioral, and gene expression phenotypes resulting after a developmental exposure to Δ9-tetrahydrocannabinol (THC) or CBD. Zebrafish were exposed from blastula through larval stage (96 hour post fertilization) to 0.3, 0.6, 1.25, 2.5, 5 mg/L (1, 2, 4, 8, 16 μM) THC or 0.07, 0.1, 0.3, 0.6, 1.25 mg/L CBD (0.25, 0.5, 1, 2, 4 μM). Despite the similarity in THC and CBD dysmorphologies, i.e., edemas, curved axis, eye/snout/jaw/trunk/fin deformities, swim bladder distention, and behavioral abnormalities, the LC50 for CBD (0.53 mg/L) was nearly seven times lower than THC (3.65 mg/L). At 96 hpf, c-fos, dazl, and vasa were differentially expressed following THC exposure, but only c-fos expression was significantly increased by CBD. CBD was more bioconcentrated compared to THC despite higher THC water concentrations. This work supports the potential for persistent developmental impacts of cannabinoid exposure, but more studies are needed to assess latent effects and their molecular mechanisms of toxicity.

PMID: 29106691 [PubMed – as supplied by publisher]

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The use of cannabidiol for seizure management in patients with brain tumor-related epilepsy.

Category : Epilepsia

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The use of cannabidiol for seizure management in patients with brain tumor-related epilepsy.

Neurocase. 2017 Oct 24;:1-5

Authors: Warren PP, Bebin EM, Nabors LB, Szaflarski JP

Abstract
Epilepsy, commonly encountered by patients with brain tumors, is often refractory to standard therapies. Our aim was to examine the safety and efficacy of pharmaceutical grade cannabidiol (CBD; Epidiolex, GW Pharmaceuticals) in those patients with epilepsy with concomitant tumors enrolled in The University of Alabama at Birmingham CBD Program (NCT02700412 and NCT02695537). Of the three patients with refractory seizures and a history of a primary brain tumor, two had improvement in seizure frequency and all three had improvement in seizure severity. These pilot results suggest that CBD should be further studied for the treatment of brain tumor-related epilepsy.

PMID: 29063814 [PubMed – as supplied by publisher]

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A case for cannabidiol in Wolf-Hirschhorn syndrome seizure management.

Category : Epilepsia

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A case for cannabidiol in Wolf-Hirschhorn syndrome seizure management.

Am J Med Genet A. 2017 Feb;173(2):324-326

Authors: Ho KS, Wassman ER

Abstract
Complex, and sometimes intractable, seizures affect the quality of life and cognitive development of over 90% of individuals with Wolf-Hirschhorn syndrome (WHS). Fine resolution genotype-phenotype mapping of the WHS locus recently identified a candidate gene whose probable function has led to insights into a mechanism connecting WHS seizures with those of Dravet syndrome, a distinct condition caused by mutations in SCN1A and SCN1B. In addition to this possible molecular mechanistic connection, these disorders’ seizures share a strikingly similar constellation of features, including clinical presentation, seizure types, early age of onset, EEG pattern, and responses to specific anti-epileptic drugs. Based in part on these similarities, we suggest that a highly successful Phase III clinical trial of a formulation of cannabidiol for Dravet syndrome seizures may be directly translatable into possible benefits for WHS individuals with challenging seizure patterns. © 2016 Wiley Periodicals, Inc.

PMID: 28102593 [PubMed – indexed for MEDLINE]

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Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome.

Category : Epilepsia

Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome.

Proc Natl Acad Sci U S A. 2017 Oct 02;:

Authors: Kaplan JS, Stella N, Catterall WA, Westenbroek RE

Abstract
Worldwide medicinal use of cannabis is rapidly escalating, despite limited evidence of its efficacy from preclinical and clinical studies. Here we show that cannabidiol (CBD) effectively reduced seizures and autistic-like social deficits in a well-validated mouse genetic model of Dravet syndrome (DS), a severe childhood epilepsy disorder caused by loss-of-function mutations in the brain voltage-gated sodium channel NaV1.1. The duration and severity of thermally induced seizures and the frequency of spontaneous seizures were substantially decreased. Treatment with lower doses of CBD also improved autistic-like social interaction deficits in DS mice. Phenotypic rescue was associated with restoration of the excitability of inhibitory interneurons in the hippocampal dentate gyrus, an important area for seizure propagation. Reduced excitability of dentate granule neurons in response to strong depolarizing stimuli was also observed. The beneficial effects of CBD on inhibitory neurotransmission were mimicked and occluded by an antagonist of GPR55, suggesting that therapeutic effects of CBD are mediated through this lipid-activated G protein-coupled receptor. Our results provide critical preclinical evidence supporting treatment of epilepsy and autistic-like behaviors linked to DS with CBD. We also introduce antagonism of GPR55 as a potential therapeutic approach by illustrating its beneficial effects in DS mice. Our study provides essential preclinical evidence needed to build a sound scientific basis for increased medicinal use of CBD.

PMID: 28973916 [PubMed – as supplied by publisher]

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A Resurging Boom in New Drugs for Epilepsy and Brain Disorders.

Category : Epilepsia

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A Resurging Boom in New Drugs for Epilepsy and Brain Disorders.

Expert Rev Clin Pharmacol. 2017 Sep 28;:

Authors: Younus I, Reddy DS

Abstract
INTRODUCTION: Epilepsy is one of the most common neurological diseases affecting approximately 50 million people worldwide. Despite many advances in epilepsy research, nearly a third of patients with epilepsy have refractory or pharmacoresistant epilepsy. Despite the approval of a dozen antiepileptic drugs (AEDs) over the past decade, there are no agents that halt the development of epilepsy. Thus, newer and better AEDs that can prevent refractory seizures and modify the disease are needed for curing epilepsy. Areas Covered: In this article, we highlight the recent advances and emerging trends in new and innovative drugs for epilepsy and seizure disorders. We review in detail top new drugs that are currently in clinical trials or agents that are under development and have novel mechanisms of action. Expert Commentary: Among the new agents under clinical investigation, the majority were originally developed for treating other neurological diseases (everolimus, fenfluramine, nalutozan, bumetanide, and valnoctamide); several have mechanisms of action similar to those of conventional AEDs (AP, ganaxolone, and YKP3089); and some new agents represent novel mechanisms of actions (huperzine-A, cannabidiol, tonabersat, and VX-765).

PMID: 28956955 [PubMed – as supplied by publisher]

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