CANNABINOIDS AND EPILEPSY DICIEMBRE 2018

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1. Paediatr Child Health. 2018 Sep
Cannabis for the treatment of paediatric epilepsy? An update for Canadian paediatricians. James Huntsman R(1)(2), Tang-Wai R(1)(3), Acton B(4), Alcorn J(1)(5), William Lyon A(1)(6), David Mousseau D(1)(7), Seifert B(1)(8), Laprairie R(1)(5), Prosser-Loose E(9), Ondrej Hanuš L(10). Author information: (1)Cannabinoid Research Initiative of Saskatchewan (CRIS), University of Saskatchewan, Saskatoon, Saskatchewan. (2)Division of Pediatric Neurology, Department of Pediatrics, University of Saskatchewan, Saskatoon, Saskatchewan. (3)Division of Pediatric Neurology, Department of Pediatrics, University of Alberta, Edmonton, Alberta. (4)Saskatchewan Health Authority, Saskatoon Area and Department of Psychology, University of Saskatchewan, Saskatoon, Saskatchewan. (5)College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan. (6)Department of Pathology and Laboratory Medicine, Saskatchewan Health Authority, Saskatoon, Saskatchewan. (7)Cell Signalling Laboratory, Departments of Psychiatry and Physiology, University of Saskatchewan, Saskatoon, Saskatchewan. (8)Department of Pharmaceutical Services, Saskatchewan Health Authority, Saskatoon, Saskatchewan. (9)Department of Pediatrics, University of Saskatchewan, Saskatoon, Saskatchewan. (10)Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University, Ein Kerem Campus, Jerusalem. The plant Cannabis sativa produces over 140 known cannabinoids. These chemicals generate considerable interest in the medical research community for their possible application to several intractable disease conditions. Recent reports have prompted parents to strongly consider Cannabis products to treat their children with drug resistant epilepsy. Physicians, though, are reluctant to prescribe Cannabis products due to confusion about their regulatory status and limited clinical data supporting their use. We provide the general paediatrician with a brief review of cannabinoid biology, the literature regarding their use in children with drug resistant epilepsy, the current Health Canada and Canadian Paediatric Society recommendations and also the regulations from the physician regulatory bodies for each province and territory. Given the complexities of conducting research on Cannabis products for children with epilepsy, we also discuss outstanding research objectives that must be addressed to support Cannabis products as an accepted treatment option for children with refractory epilepsy.
2. Front Integr Neurosci. 2018 Oct Cannabis Therapeutics and the Future of Neurology. Russo EB(1). Author information: (1)International Cannabis and Cannabinoids Institute (ICCI), Prague, Czechia. Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes. While cannabis-based medicines have demonstrated safety, efficacy and consistency sufficient for regulatory approval in spasticity in multiple sclerosis (MS), and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges remain. This review will examine the intriguing promise that recent discoveries regarding cannabis-based medicines offer to neurological therapeutics by incorporating the neutral phytocannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the putative treatment of five syndromes, currently labeled recalcitrant to therapeutic success, and wherein improved pharmacological intervention is required: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE). Current basic science and clinical investigations support the safety and efficacy of such interventions in treatment of these currently intractable conditions, that in some cases share pathological processes, and the plausibility of interventions that harness endocannabinoid mechanisms, whether mediated via direct activity on CB1 and CB2 (tetrahydrocannabinol, THC, caryophyllene), peroxisome proliferator-activated receptor-gamma (PPARγ; THCA), 5-HT1A (CBD, CBDA) or even nutritional approaches utilizing prebiotics and probiotics. The inherent polypharmaceutical properties of cannabis botanicals offer distinct advantages over the current single-target pharmaceutical model and portend to revolutionize neurological treatment into a new reality of effective interventional and even preventative treatment. 3. Dev Med Child Neurol. 2018 Nov Efficacy of cannabinoids in paediatric epilepsy. Ali S(1), Scheffer IE(2)(3)(4), Sadleir LG(1). Author information: (1)Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand. (2)Departments of Medicine and Paediatrics, University of Melbourne, Melbourne, Victoria, Australia. (3)Austin Health and Royal Children's Hospital, Heidelberg, Victoria, Australia. (4)Florey and Murdoch Children's Research Institutes, Melbourne, Victoria, Australia. There are hundreds of compounds found in the marijuana plant, each contributing differently to the antiepileptic and psychiatric effects. Cannabidiol (CBD) has the most evidence of antiepileptic efficacy and does not have the psychoactive effects of ∆9 -tetrahydrocannabinol. CBD does not act via cannabinoid receptors and its antiepileptic mechanism of action is unknown. Despite considerable community interest in the use of CBD for paediatric epilepsy, there has been little evidence for its use apart from anecdotal reports, until the last year. Three randomized, placebo-controlled, double-blind trials in Dravet syndrome and Lennox-Gastaut syndrome found that CBD produced a 38% to 41% median reduction in all seizures compared to 13% to 19% on placebo. Similarly, CBD resulted in a 39% to 46% responder rate (50% convulsive or drop-seizure reduction) compared to 14% to 27% on placebo. CBD was well tolerated; however, sedation, diarrhoea, and decreased appetite were frequent. CBD shows similar efficacy to established antiepileptic drugs. WHAT THIS PAPER ADDS: Cannabidiol (CBD) shows similar efficacy in the severe paediatric epilepsies to other antiepileptic drugs. Careful down-titration of benzodiazepines is essential to minimize sedation with adjunctive CBD. © 2018 Mac Keith Press.
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