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Cannabinoids and epilepsy

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https://www.readbyqxmd.com/read/29106691/developmental-effects-of-cannabidiol-and-%C3%AE-9-tetrahydrocannabinol-in-zebrafish
#1
Dennis R Carty, Cammi Thornton, James Gledhill, Kristine L Willett
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...
November 2, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29105060/cannabinoid-receptor-1-2-double-knockout-mice-develop-epilepsy
#2
Shane Rowley, Xiaofei Sun, Isabel V Lima, Alexandra Tavenier, Antonio Carlos Pinheiro de Oliveira, Sudhansu K Dey, Steve C Danzer
The endocannabinoid system has gained attention as an important modulator of activity in the central nervous system. Initial studies focused on cannabinoid receptor 1 (CB1), which is widely expressed in the brain, but recent work also implicates cannabinoid receptor 2 (CB2) in modulating neuronal activity. Both receptors are capable of reducing neuronal activity, generating interest in cannabinoid receptor agonists as potential anticonvulsants. CB1 (Cnr1) and CB2 (Cnr2) single-knockout mice have been generated, with the former showing heightened seizure sensitivity, but not overt seizures...
November 3, 2017: Epilepsia
https://www.readbyqxmd.com/read/29061872/medical-cannabinoids-in-children-and-adolescents-a-systematic-review
#3
REVIEW
Shane Shucheng Wong, Timothy E Wilens
CONTEXT: Legalization of medical marijuana in many states has led to a widening gap between the accessibility and the evidence for cannabinoids as a medical treatment. OBJECTIVE: To systematically review published reports to identify the evidence base of cannabinoids as a medical treatment in children and adolescents. DATA SOURCES: Based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a search of PubMed, Medline, and the Cumulative Index to Nursing and Allied Health Literature databases was conducted in May 2017...
November 2017: Pediatrics
https://www.readbyqxmd.com/read/28991183/orexin-receptor-multimerization-versus-functional-interactions-neuropharmacological-implications-for-opioid-and-cannabinoid-signalling-and-pharmacogenetics
#4
Miles D Thompson, Takeshi Sakurai, Innocenzo Rainero, Mary C Maj, Jyrki P Kukkonen
Orexins/hypocretins are neuropeptides formed by proteolytic cleavage of a precursor peptide, which are produced by neurons found in the lateral hypothalamus. The G protein-coupled receptors (GPCRs) for these ligands, the OX₁ and OX₂ orexin receptors, are more widely expressed throughout the central nervous system. The orexin/hypocretin system has been implicated in many pathways, and its dysregulation is under investigation in a number of diseases. Disorders in which orexinergic mechanisms are being investigated include narcolepsy, idiopathic sleep disorders, cluster headache and migraine...
October 8, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28979317/the-role-of-bk-channels-in-antiseizure-action-of-the-cb1-receptor-agonist-acea-in-maximal-electroshock-and-pentylenetetrazole-models-of-seizure-in-mice
#5
Sina Asaadi, Mohammad Jahanbakhshi, Mahmoud Lotfinia, Nima Naderi
The anticonvulsant effect of cannabinoid compound has been shown in various models of seizure. On the other hand, there are controversial findings about the role of large conductance calcium-activated potassium (BK) channels in the pathogenesis of epilepsy. Also, there is no data regarding the effect of co-administration of cannabinoid type 1 (CB1) receptor agonists and BK channels antagonists in the acute models of seizure in mice. In this study, the effect of arachidonyl-2'-chloroethylamide (ACEA), a CB1 receptor agonist, and a BK channel antagonist, paxilline, either alone or in combination was investigated...
2017: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/28898306/-cannabis-use-in-epilepsy-current-situation-in-argentina-and-abroad
#6
Silvia Kochen
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...
November 2016: Vertex: Revista Argentina de Psiquiatriá
https://www.readbyqxmd.com/read/28894217/the-faah-inhibitor-urb597-suppresses-hippocampal-maximal-dentate-afterdischarges-and-restores-seizure-induced-impairment-of-short-and-long-term-synaptic-plasticity
#7
Roberto Colangeli, Massimo Pierucci, Arcangelo Benigno, Giuseppe Campiani, Sefania Butini, Giuseppe Di Giovanni
Synthetic cannabinoids and phytocannabinoids have been shown to suppress seizures both in humans and experimental models of epilepsy. However, they generally have a detrimental effect on memory and memory-related processes. Here we compared the effect of the inhibition of the endocannabinoid (eCB) degradation versus synthetic CB agonist on limbic seizures induced by maximal dentate activation (MDA) acute kindling. Moreover, we investigated the dentate gyrus (DG) granule cell reactivity and synaptic plasticity in naïve and in MDA-kindled anaesthetised rats...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28882919/a-randomised-controlled-cross-over-double-blind-pilot-study-protocol-on-thc-cbd-oromucosal-spray-efficacy-as-an-add-on-therapy-for-post-stroke-spasticity
#8
Lucio Marinelli, Maurizio Balestrino, Laura Mori, Luca Puce, Gian Marco Rosa, Laura Giorello, Antonio Currà, Francesco Fattapposta, Carlo Serrati, Carlo Gandolfo, Giovanni Abbruzzese, Carlo Trompetto
INTRODUCTION: Stroke is the most disabling neurological disorder and often causes spasticity. Transmucosal cannabinoids (tetrahydrocannabinol and cannabidiol (THC:CBD), Sativex) is currently available to treat spasticity-associated symptoms in patients with multiple sclerosis. Cannabinoids are being considered useful also in the treatment of pain, nausea and epilepsy, but may bear and increased risk for cardiovascular events. Spasticity is often assessed with subjective and clinical rating scales, which are unable to measure the increased excitability of the monosynaptic reflex, considered the hallmark of spasticity...
September 7, 2017: BMJ Open
https://www.readbyqxmd.com/read/28859122/effects-of-arachidonyl-2-chloroethylamide-acea-on-the-protective-action-of-various-antiepileptic-drugs-in-the-6-hz-corneal-stimulation-model-in-mice
#9
Jarogniew J Luszczki, Pawel Patrzylas, Miroslaw Zagaja, Marta Andres-Mach, Katarzyna Zaluska, Maria W Kondrat-Wrobel, Monika Szpringer, Jaroslaw Chmielewski, Magdalena Florek-Luszczki
Accumulating evidence indicates that cannabinoid CB1 receptor ligands play a pivotal role in seizures, not only in preclinical studies on animals, but also in clinical settings. This study was aimed at characterizing the influence of arachidonyl-2'-chloroethylamide (ACEA-a selective cannabinoid CB1 receptor agonist) co-administered with phenylmethylsulfonyl fluoride (PMSF) on the anticonvulsant potency of various antiepileptic drugs (clobazam, lacosamide, levetiracetam, phenobarbital, tiagabine and valproate) in the 6-Hz corneal stimulation model...
2017: PloS One
https://www.readbyqxmd.com/read/28845714/the-potential-role-of-cannabinoids-in-epilepsy-treatment
#10
Carmen De Caro, Antonio Leo, Rita Citraro, Caterina De Sarro, Roberto Russo, Antonio Calignano, Emilio Russo
Epilepsy is one of the world's oldest recognized and prevalent neurological diseases. It has a great negative impact on patients' quality of life (QOL) as a consequence of treatment resistant seizures in about 30% of patients together with drugs' side effects and comorbidities. Therefore, new drugs are needed and cannabinoids, above all cannabidiol, have recently gathered attention. Areas covered: This review summarizes the scientific data from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including drugs acting on the endocannabinoid system...
September 4, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28821005/anticonvulsant-effect-of-cannabidiol-in-the-pentylenetetrazole-model-pharmacological-mechanisms-electroencephalographic-profile-and-brain-cytokine-levels
#11
Luciano R Vilela, Isabel V Lima, Érica B Kunsch, Hyorrana Priscila P Pinto, Aline S de Miranda, Érica Leandro M Vieira, Antônio Carlos P de Oliveira, Marcio Flávio D Moraes, Antônio L Teixeira, Fabricio A Moreira
Cannabidiol (CBD), the main nonpsychotomimetic compound from Cannabis sativa, inhibits experimental seizures in animal models and alleviates certain types of intractable epilepsies in patients. Its pharmacological profile, however, is still uncertain. Here we tested the hypothesis that CBD anticonvulsant mechanisms are prevented by cannabinoid (CB1 and CB2) and vanilloid (TRPV1) receptor blockers. We also investigated its effects on electroencephalographic (EEG) activity and hippocampal cytokines in the pentylenetetrazole (PTZ) model...
August 15, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28758944/interactions-between-the-kynurenine-and-the-endocannabinoid-system-with-special-emphasis-on-migraine
#12
REVIEW
Gábor Nagy-Grócz, Ferenc Zádor, Szabolcs Dvorácskó, Zsuzsanna Bohár, Sándor Benyhe, Csaba Tömböly, Árpád Párdutz, László Vécsei
Both the kynurenine and the endocannabinoid systems are involved in several neurological disorders, such as migraine and there are increasing number of reports demonstrating that there are interactions of two systems. Although their cooperation has not yet been implicated in migraine, there are reports suggesting this possibility. Additionally, the individual role of the endocannabinoid and kynurenine system in migraine is reviewed here first, focusing on endocannabinoids, kynurenine metabolites, in particular kynurenic acid...
July 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28753497/disease-modifying-effect-of-atipamezole-in-a-model-of-post-traumatic-epilepsy
#13
Jari Nissinen, Pedro Andrade, Teemu Natunen, Mikko Hiltunen, Tarja Malm, Katja Kanninen, Joana I Soares, Olena Shatillo, Jukka Sallinen, Xavier Ekolle Ndode-Ekane, Asla Pitkänen
Treatment of TBI remains a major unmet medical need, with 2.5 million new cases of traumatic brain injury (TBI) each year in Europe and 1.5 million in the USA. This single-center proof-of-concept preclinical study tested the hypothesis that pharmacologic neurostimulation with proconvulsants, either atipamezole, a selective α2-adrenoceptor antagonist, or the cannabinoid receptor 1 antagonist SR141716A, as monotherapy would improve functional recovery after TBI. A total of 404 adult Sprague-Dawley male rats were randomized into two groups: sham-injured or lateral fluid-percussion-induced TBI...
July 12, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28691717/interaction-between-urethane-and-cannabinoid-cb1-receptor-agonist-and-antagonist-in-penicillin-induced-epileptiform-activity
#14
Gokhan Arslan, Sabiha Kubra Alici, Mustafa Ayyildiz, Erdal Agar
Previous experimental studies have shown that various anesthetics alter the effects of cannabinoid agonists and antagonists on the cardiac response to different stimuli. Since no data have shown an interaction between urethane and cannabinoid signaling in epilepsy, we examined the suitability of urethane with regard to testing the effects of a cannabinoid CB1 receptor agonist and an antagonist on penicillin-induced epileptiform activity in rats. Permanent screw electrodes for electrocorticographic (ECoG) recordings, and a permanent cannula for administration of the substances to the brain ventricles, were placed into the cranium of rats...
2017: Acta Neurobiologiae Experimentalis
https://www.readbyqxmd.com/read/28691158/anticonvulsant-effect-of-cannabinoid-receptor-agonists-in-models-of-seizures-in-developing-rats
#15
Megan N Huizenga, Evan Wicker, Veronica C Beck, Patrick A Forcelli
OBJECTIVE: Although drugs targeting the cannabinoid system (e.g., CB1 receptor agonists) display anticonvulsant efficacy in adult animal models of seizures/epilepsy, they remain unexplored in developing animal models. However, cannabinoid system functions emerge early in development, providing a rationale for targeting this system in neonates. We examined the therapeutic potential of drugs targeting the cannabinoid system in three seizure models in developing rats. METHODS: Postnatal day (P) 10, Sprague-Dawley rat pups were challenged with the chemoconvulsant methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) or pentylenetetrazole (PTZ), after treatment with either CB1/2 mixed agonist (WIN 55,212-2), CB1 agonist (arachidonyl-2'-chloroethylamide [ACEA]), CB2 agonist (HU-308), CB1 antagonist (AM-251), CB2 antagonist (AM-630), fatty acid amide hydrolase inhibitor (URB-597), or G protein-coupled receptor 55 agonist (O-1602)...
September 2017: Epilepsia
https://www.readbyqxmd.com/read/28579820/cannabis-and-intractable-chronic-pain-an-explorative-retrospective-analysis-of-italian-cohort-of-614-patients
#16
Guido Fanelli, Giuliano De Carolis, Claudio Leonardi, Adele Longobardi, Ennio Sarli, Massimo Allegri, Michael E Schatman
BACKGROUND: Despite growing interest in the therapeutic use of cannabis to manage chronic pain, only limited data that address these issues are available. In recent years, a number of nations have introduced specific laws to allow patients to use cannabis preparations to treat a variety of medical conditions. In 2015, the Italian government authorized the use of cannabis to treat several diseases, including chronic pain generally, spasticity in multiple sclerosis, cachexia and anorexia among AIDS and cancer patients, glaucoma, Tourette syndrome, and certain types of epilepsy...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28538129/cannabinoids-for-epilepsy-real-data-at-last
#17
EDITORIAL
Samuel F Berkovic
New England Journal of Medicine, Volume 376, Issue 21, Page 2075-2076, May 2017.
May 25, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28534260/pharmacogenetics-of-cannabinoids
#18
Szymon Hryhorowicz, Michal Walczak, Oliwia Zakerska-Banaszak, Ryszard Słomski, Marzena Skrzypczak-Zielińska
Although the application of medical marijuana and cannabinoid drugs is controversial, it is a part of modern-day medicine. The list of diseases in which cannabinoids are promoted as a treatment is constantly expanding. Cases of significant improvement in patients with a very poor prognosis of glioma or epilepsy have already been described. However, the occurrence of side effects is still difficult to estimate, and the current knowledge of the therapeutic effects of cannabinoids is still insufficient. In our opinion, the answers to many questions and concerns regarding the medical use of cannabis can be provided by pharmacogenetics...
May 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28454984/cannabidiol-treatment-for-refractory-seizures-in-sturge-weber-syndrome
#19
Emma H Kaplan, Elizabeth A Offermann, Jacqueline W Sievers, Anne M Comi
BACKGROUND: Sturge-Weber syndrome results in leptomeningeal vascular malformations, medically refractory epilepsy, stroke(s), and cognitive impairments. Cannabidiol, a cannabinoid without psychoactive properties, has been demonstrated in preclinical models to possibly have anticonvulsant, antioxidant, and neuroprotective actions. METHODS: Five subjects with Sturge-Weber syndrome brain involvement and treatment-resistant epilepsy were enrolled. Motor seizure frequency, quality of life, and adverse events were recorded from the eighth week of the pretreatment period, eight weeks after starting maintenance dose (week 14), and the most recent visit...
June 2017: Pediatric Neurology
https://www.readbyqxmd.com/read/28441341/a-long-term-treatment-with-arachidonyl-2-chloroethylamide-combined-with-valproate-increases-neurogenesis-in-a-mouse-pilocarpine-model-of-epilepsy
#20
Marta Andres-Mach, Mirosław Zagaja, Agnieszka Haratym-Maj, Radosław Rola, Maciej Maj, Joanna Haratym, Monika Dudra-Jastrzębska, Jarogniew J Łuszczki
Rational polytherapy in the treatment of refractory epilepsy has been the main therapeutic modality for several years. In treatment with two or more antiepileptic drugs (AEDs), it is of particular importance that AEDs be selected based on their high anticonvulsant properties, minimal side effects, and impact on the formation of new neurons. The aim of the study was to conduct an in vivo evaluation of the relationship between treatments with synthetic cannabinoid arachidonyl-2'-chloroethylamide (ACEA) alone or in combination with valproic acid (VPA) and hippocampal neurogenesis in a mouse pilocarpine model of epilepsy...
April 25, 2017: International Journal of Molecular Sciences
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