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Cannabinoids and epilepsy

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https://www.readbyqxmd.com/read/27851727/high-resolution-crystal-structure-of-the-human-cb1-cannabinoid-receptor
#1
Zhenhua Shao, Jie Yin, Karen Chapman, Magdalena Grzemska, Lindsay Clark, Junmei Wang, Daniel M Rosenbaum
The human cannabinoid G-protein-coupled receptors (GPCRs) CB1 and CB2 mediate the functional responses to the endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG), as well as the widely consumed plant (phyto)cannabinoid Δ(9)-tetrahydrocannabinol (THC)(1). The cannabinoid receptors have been the targets of intensive drug discovery efforts owing to the therapeutic potential of modulators for controlling pain(2), epilepsy(3), obesity(4), and other maladies. Although much progress has recently been made in understanding the biophysical properties of GPCRs, investigations of the molecular mechanisms of the cannabinoids and their receptors have lacked high-resolution structural data...
November 16, 2016: Nature
https://www.readbyqxmd.com/read/27810514/endogenous-cannabinoid-system-alterations-and-their-role-in-epileptogenesis-after-brain-injury-in-rat
#2
Xiu Wang, Yao Wang, Chao Zhang, Chang Liu, Hai-Feng Yang, Wen-Han Hu, Jian-Guo Zhang, Kai Zhang
Post-traumatic epilepsy (PTE) is one of the most common complications resulting from brain injury, however, antiepileptic drugs usually fail to prevent it. Several lines of evidence have demonstrated that the endogenous cannabinoid system (ECS) plays a pivotal role during epileptogenesis in several animal models. A recent study has shown that a cannabinoid type 1 (CB1) receptor antagonist could suppress long-term neuron hyperexcitability after brain injury, but the underlying mechanisms remain largely unknown...
December 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27790143/a-personal-retrospective-elevating-anandamide-aea-by-targeting-fatty-acid-amide-hydrolase-faah-and-the-fatty-acid-binding-proteins-fabps
#3
Dale G Deutsch
This perspective was adapted from a Career Achievement Award talk given at the International Cannabinoid Research Society Symposium in Bukovina, Poland on June 27, 2016. As a biochemist working in the neurosciences, I was always fascinated with neurotransmitter inactivation. In 1993 we identified an enzyme activity that breaks down anandamide. We called the enzyme anandamide amidase, now called FAAH. We and other laboratories developed FAAH inhibitors that were useful reagents that also proved to have beneficial physiological effects and until recently, new generations of inhibitors were in clinical trials...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27790138/splendor-in-the-grass-a-pilot-study-assessing-the-impact-of-medical-marijuana-on-executive-function
#4
Staci A Gruber, Kelly A Sagar, Mary K Dahlgren, Megan T Racine, Rosemary T Smith, Scott E Lukas
Currently, 25 states and Washington DC have enacted full medical marijuana (MMJ) programs while 18 states allow limited access to MMJ products. Limited access states permit low (or zero) tetrahydrocannabinol (THC) and high cannabidiol (CBD) products to treat specified conditions such as uncontrolled epilepsy. Although MMJ products are derived from the same plant species as recreational MJ, they are often selected for their unique cannabinoid constituents and ratios, not typically sought by recreational users, which may impact neurocognitive outcomes...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27789118/adverse-structural-and-functional-effects-of-marijuana-on-the-brain-evidence-reviewed
#5
REVIEW
David E Mandelbaum, Suzanne M de la Monte
The growing use and legalization of cannabis are leading to increased exposures across all age groups, including in adolescence. The touting of its medicinal values stems from anecdotal reports related to treatment of a broad range of illnesses including epilepsy, multiple sclerosis, muscle spasms, arthritis, obesity, cancer, Alzheimer disease, Parkinson disease, post-traumatic stress, inflammatory bowel disease, and anxiety. However, it is essential that anecdotal data and the high level of interest in this treatment not obscure objective assessments of any potential and realized short- and long-term adverse effects of cannabis, particularly with respect to age of onset and chronicity of exposure...
September 13, 2016: Pediatric Neurology
https://www.readbyqxmd.com/read/27763968/effects-of-marijuana-on-ictal-and-interictal-eeg-activity-in-idiopathic-generalized-epilepsy
#6
Sanjeev Sivakumar, Deepti Zutshi, Navid Seraji-Bozorgzad, Aashit Shah
Marijuana-based treatment for refractory epilepsy shows promise in surveys, case series and clinical trials. However, literature on their electroencephalography (EEG) effects is sparse. Our objective is to analyze the effect of marijuana on EEG in a 24-year-old patient with idiopathic generalized epilepsy (IGE) treated with cannabis. We blindly reviewed three long-term EEGs-a 24-hour study while only on antiepileptic drugs (AEDs), a 72-hour EEG with Cannabis indica smoked on days one and three in addition to AEDs and a 48-hour EEG with combination C...
October 18, 2016: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
https://www.readbyqxmd.com/read/27746737/%C3%AE-9-thc-intoxication-by-cannabidiol-enriched-cannabis-extract-in-two-children-with-refractory-epilepsy-full-remission-after-switching-to-purified-cannabidiol
#7
José A S Crippa, Ana C S Crippa, Jaime E C Hallak, Rocio Martín-Santos, Antonio W Zuardi
Animal studies and preliminary clinical trials have shown that cannabidiol (CBD)-enriched extracts may have beneficial effects for children with treatment-resistant epilepsy. However, these compounds are not yet registered as medicines by regulatory agencies. We describe the cases of two children with treatment-resistant epilepsy (Case A with left frontal dysplasia and Case B with Dravet Syndrome) with initial symptom improvement after the introduction of CBD extracts followed by seizure worsening after a short time...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27663280/pharmacokinetic-pharmacodynamic-influence-of-n-palmitoylethanolamine-arachidonyl-2-chloroethylamide-and-win-55-212-2-on-the-anticonvulsant-activity-of-antiepileptic-drugs-against-audiogenic-seizures-in-dba-2-mice
#8
Rita Citraro, Emilio Russo, Antonio Leo, Roberto Russo, Carmen Avagliano, Michele Navarra, Antonio Calignano, Giovambattista De Sarro
We evaluated the effects of ACEA (selective cannabinoid (CB)1 receptor agonist), WIN 55,212-2 mesylate (WIN; non-selective CB1 and CB2 receptor agonist) and N-palmitoylethanolamine (PEA; an endogenous fatty acid of ethanolamide) in DBA/2 mice, a genetic model of reflex audiogenic epilepsy. PEA, ACEA or WIN intraperitoneal (i.p.) administration decreased the severity of tonic-clonic seizures. We also studied the effects of PEA, WIN or ACEA after co-administration with NIDA-41020 (CB1 receptor antagonist) or GW6471 (PPAR-α antagonist) and compared the effects of WIN, ACEA and PEA in order to clarify their mechanisms of action...
September 20, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27608434/the-cannabinoid-cb2-receptor-specific-agonist-am1241-increases-pentylenetetrazole-induced-seizure-severity-in-wistar-rats
#9
Cristiane R de Carvalho, Alexandre A Hoeller, Pedro L C Franco, Athos P S Martini, Flávia M S Soares, Katia Lin, Rui D Prediger, Benjamin J Whalley, Roger Walz
The potential efficacy of cannabinoid receptor ligands for the treatment of epilepsy remains controversial; cannabis components that act via cannabinoid type 1 (CB1) receptors produce anticonvulsant effects in animal models despite treatment with the CB receptor agonist reliably inducing convulsions in various species. Moreover, the potential role of cannabinoid receptor type 2 (CB2) to modulate seizures remains under-investigated. This study assessed the effects of the selective CB2 receptor agonist, AM1241, on pentylenetetrazole (PTZ)-induced seizures in rats...
August 29, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/27587196/from-cannabis-to-cannabidiol-to-treat-epilepsy-where-are-we
#10
Pellegrino Lippiello, Simona Balestrini, Antonio Leo, Antonietta Coppola, Rita Citraro, Maurizio Elia, Emilio Russo, Giovambattista De Sarro
BACKGROUND: Several antiepileptic drugs (AEDs), about 25, are currently clinically available for the treatment of patients with epilepsy. Despite this armamentarium and the many recently introduced AEDs, no major advances have been achieved considering the number of drug resistant patients, while many benefits have been indeed obtained for other clinical outcomes (e.g. better tolerability, less interactions). Cannabinoids have long been studied for their potential therapeutical use and more recently phytocannabinoids have been considered a valuable tool for the treatment of several neurological disorders including epilepsy...
August 31, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27520083/the-cannabinoid-receptor-agonist-win55-212-reduces-consequences-of-status-epilepticus-in-rats
#11
Elena M Suleymanova, Vitalia A Shangaraeva, Clementina M van Rijn, LyudmilaV Vinogradova
An acute brain insult can cause a spectrum of primary and secondary pathologies including increased risk for epilepsy, mortality and neurodegeneration. The endocannabinoid system, involved in protecting the brain against network hyperexcitability and excitotoxicity, is profoundly dysregulated by acute brain insults. We hypothesize that post-insult dysregulation of the endocannabinoid signaling may contribute to deleterious effects of an acute brain injury and potentiation of endocannabinoid transmission soon after an insult may reduce its pathological outcomes...
August 9, 2016: Neuroscience
https://www.readbyqxmd.com/read/27267376/aberrant-epilepsy-associated-mutant-nav1-6-sodium-channel-activity-can-be-targeted-with-cannabidiol
#12
Reesha R Patel, Cindy Barbosa, Tatiana Brustovetsky, Nickolay Brustovetsky, Theodore R Cummins
Mutations in brain isoforms of voltage-gated sodium channels have been identified in patients with distinct epileptic phenotypes. Clinically, these patients often do not respond well to classic anti-epileptics and many remain refractory to treatment. Exogenous as well as endogenous cannabinoids have been shown to target voltage-gated sodium channels and cannabidiol has recently received attention for its potential efficacy in the treatment of childhood epilepsies. In this study, we further investigated the ability of cannabinoids to modulate sodium currents from wild-type and epilepsy-associated mutant voltage-gated sodium channels...
August 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27215115/-medical-cannabis
#13
Timna Naftali
The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea and inflammation. Current research is inspecting the use of cannabis for many diseases, including multiple sclerosis, epilepsy, dystonia, and chronic pain. In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and:pain and diarrhea in Crohn's disease. Despite their therapeutic potential, cannabinoids are not free of side effects including psychosis, anxiety, paranoia, dependence and abuse. Controlled clinical studies investigating the therapeutic potential of cannabis are few and small, whereas pressure for expanding cannabis use is increasing...
February 2016: Harefuah
https://www.readbyqxmd.com/read/27113252/advances-of-molecular-imaging-in-epilepsy
#14
REVIEW
Marian Galovic, Matthias Koepp
Positron emission tomography (PET) is a neuroimaging method that offers insights into the molecular functioning of a human brain. It has been widely used to study metabolic and neurotransmitter abnormalities in people with epilepsy. This article reviews the development of several PET radioligands and their application in studying the molecular mechanisms of epilepsy. Over the last decade, tracers binding to serotonin and γ-aminobutyric acid (GABA) receptors have been used to delineate the location of the epileptic focus...
June 2016: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/27086601/endocannabinoid-system-a-multi-facet-therapeutic-target
#15
REVIEW
Rimplejeet Kaur, Sneha R Ambwani, Surjit Singh
Cannabis sativa is also popularly known as marijuana. It has been cultivated and used by man for recreational and medicinal purposes since many centuries. Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries. The research of drugs acting on endocannabinoid system has seen many ups and downs in the recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve "protective role" in many medical conditions...
2016: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/27069631/analysis-of-endocannabinoid-signaling-elements-and-related-proteins-in-lymphocytes-of-patients-with-dravet-syndrome
#16
Marta Rubio, Sara Valdeolivas, Fabiana Piscitelli, Roberta Verde, Valentina Satta, Eva Barroso, Marisol Montolio, Luis Miguel Aras, Vincenzo Di Marzo, Onintza Sagredo, Javier Fernández-Ruiz
Cannabidiol (CBD) reduces seizures in childhood epilepsy syndromes including Dravet syndrome (DS). A formulation of CBD has obtained orphan drug designation for these syndromes and clinical trials are currently underway. The mechanism responsible for CBD effects is not known, although it could involve targets sensitive to CBD in other neurological disorders. We believe of interest to investigate whether these potential targets are altered in DS, in particular whether the endocannabinoid system is dysregulated...
April 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/26970948/involvement-of-trpv1-channels-in-the-activity-of-the-cannabinoid-win-55-212-2-in-an-acute-rat-model-of-temporal-lobe-epilepsy
#17
Fabio Carletti, Giuditta Gambino, Valerio Rizzo, Giuseppe Ferraro, Pierangelo Sardo
The exogenous cannabinoid agonist WIN 55,212-2, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN), has revealed to play a role on modulating the hyperexcitability phenomena in the hippocampus. Cannabinoid-mediated mechanisms of neuroprotection have recently been found to imply the modulation of transient receptor potential vanilloid 1 (TRPV1), a cationic channel subfamily that regulate synaptic excitation. In our study, we assessed the influence of pharmacological manipulation of TRPV1 function, alone and on WIN antiepileptic activity, in the Maximal Dentate Activation (MDA) acute model of temporal lobe epilepsy...
May 2016: Epilepsy Research
https://www.readbyqxmd.com/read/26902320/transient-increase-of-interleukin-1%C3%AE-after-prolonged-febrile-seizures-promotes-adult-epileptogenesis-through-long-lasting-upregulating-endocannabinoid-signaling
#18
Bo Feng, Yangshun Tang, Bin Chen, Cenglin Xu, Yi Wang, Yunjian Dai, Dengchang Wu, Junmin Zhu, Shuang Wang, Yudong Zhou, Liyun Shi, Weiwei Hu, Xia Zhang, Zhong Chen
It remains unclear how infantile febrile seizures (FS) enhance adult seizure susceptibility. Here we showed that the transient increase of interleukin-1β (IL-1β) after prolonged FS promoted adult seizure susceptibility, which was blocked by interleukin-1 receptor antagonist (IL-1Ra) within a critical time window. Postnatal administered IL-1β alone mimicked the effect of FS on adult seizure susceptibility. IL-1R1 knockout mice were not susceptible to adult seizure after prolonged FS or IL-1β treatment. Prolonged FS or early-life IL-1β treatment increased the expression of cannabinoid type 1 receptor (CB1R) for over 50 days, which was blocked by IL-1Ra or was absent in IL-1R1 knockout mice...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26892745/plant-derived-and-endogenous-cannabinoids-in-epilepsy
#19
Alberto Verrotti, Miriam Castagnino, Mauro Maccarrone, Filomena Fezza
Cannabis is one of the oldest psychotropic drugs and its anticonvulsant properties have been known since the last century. The aim of this review was to analyze the efficacy of cannabis in the treatment of epilepsy in adults and children. In addition, a description of the involvement of the endocannabinoid system in epilepsy is given in order to provide a biochemical background to the effects of endogenous cannabinoids in our body. General tolerability and adverse events associated with cannabis treatment are also investigated...
May 2016: Clinical Drug Investigation
https://www.readbyqxmd.com/read/26835389/cannabinoids-for-pediatric-epilepsy-up-in-smoke-or-real-science
#20
REVIEW
Francis M Filloux
Public interest in the use of "medical marijuana" for the treatment of childhood epilepsy has burgeoned in the last few years. This has occurred in parallel with a growing interest in "medical marijuana" in general. Physicians and pediatricians must balance their patients' desire for immediate access to these products with the tenets of evidence-based medicine. This review discusses the biochemistry of cannabis products (the phytocannabinoids) setting this in the context of the endogenous endocannabinoid system...
October 2015: Translational pediatrics
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