Category Archives: Epilepsia

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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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Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents.

Category : Epilepsia

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Current Status and Prospects for Cannabidiol Preparations as New Therapeutic Agents.

Pharmacotherapy. 2016 Jul;36(7):781-96

Authors: Fasinu PS, Phillips S, ElSohly MA, Walker LA

Abstract
States and the federal government are under growing pressure to legalize the use of cannabis products for medical purposes in the United States. Sixteen states have legalized (or decriminalized possession of) products high in cannabidiol (CBD) and with restricted ∆(9) -tetrahydrocannabinol (∆(9) -THC) content. In most of these states, the intent is for use in refractory epileptic seizures in children, but in a few states, the indications are broader. This review provides an overview of the pharmacology and toxicology of CBD; summarizes some of the regulatory, safety, and cultural issues relevant to the further exploitation of its antiepileptic or other pharmacologic activities; and assesses the current status and prospects for clinical development of CBD and CBD-rich preparations for medical use in the United States. Unlike Δ(9) -THC, CBD elicits its pharmacologic effects without exerting any significant intrinsic activity on the cannabinoid receptors, whose activation results in the psychotropic effects characteristic of Δ(9) -THC, and CBD possesses several pharmacologic activities that give it a high potential for therapeutic use. CBD exhibits neuroprotective, antiepileptic, anxiolytic, antipsychotic, and antiinflammatory properties. In combination with Δ(9) -THC, CBD has received regulatory approvals in several European countries and is currently under study in trials registered by the U.S. Food and Drug Administration in the United States. A number of states have passed legislation to allow for the use of CBD-rich, limited Δ(9) -THC-content preparations of cannabis for certain pathologic conditions. CBD is currently being studied in several clinical trials and is at different stages of clinical development for various medical indications. Judging from clinical findings reported so far, CBD and CBD-enriched preparations have great potential utility, but uncertainties regarding sourcing, long-term safety, abuse potential, and regulatory dilemmas remain.

PMID: 27285147 [PubMed – indexed for MEDLINE]

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[Cannabis use in Epilepsy. Current situation in Argentina and abroad].

Category : Epilepsia

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[Cannabis use in Epilepsy. Current situation in Argentina and abroad].

Vertex. 2016 Nov;XXVII(130):457-462

Authors: Kochen S

Abstract
Although at present we have over 20 different types of drugs for epilepsy, 30 to 40% of patients continue to have seizures. Preliminary data from human studies suggest that cannabis, cannabidiol in particular, is effective in the treatment of some patients with epilepsy. However, the available data are limited and do not allow defnitive conclusions. Only randomized clinical trials with controlled double-blind, placebo-controlled utilizing secure preparations and one or more cannabinoids, will provide comprehensive information on the effcacy and safety of use. In order to perform these trials it is necessary to have legislation authorizing the use of cannabis on epilepsy.

PMID: 28898306 [PubMed – in process]

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An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies.

Category : Epilepsia

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An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies.

Cannabis Cannabinoid Res. 2017;2(1):139-154

Authors: Iffland K, Grotenhermen F

Abstract
Introduction: This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs. Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients’ compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam’s side effects. Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking.

PMID: 28861514 [PubMed]

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