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Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence

Published on Jul 1, 2018in Journal of Neurology, Neurosurgery, and Psychiatry8.272
· DOI :10.1136/jnnp-2017-317168
Emily Stockings14
Estimated H-index: 14
(UNSW: University of New South Wales),
Dino Zagic3
Estimated H-index: 3
(UNSW: University of New South Wales)
+ 6 AuthorsLouisa Degenhardt91
Estimated H-index: 91
(UNSW: University of New South Wales)
Abstract
Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5–55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed. PROSPERO registration number CRD42017055412.
  • References (49)
  • Citations (29)
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References49
Newest
#1Eric GroceH-Index: 1
159 CitationsSource
#2Eric D. Marsh (Children's Hospital of Philadelphia)H-Index: 25
#3J. French (NYU: New York University)H-Index: 3
Last. Angus A. WilfongH-Index: 19
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Summary Background Patients with Lennox-Gastaut syndrome, a rare, severe form of epileptic encephalopathy, are frequently treatment resistant to available medications. No controlled studies have investigated the use of cannabidiol for patients with seizures associated with Lennox-Gastaut syndrome. We therefore assessed the efficacy and safety of cannabidiol as an add-on anticonvulsant therapy in this population of patients. Methods In this randomised, double-blind, placebo-controlled trial done ...
119 CitationsSource
#1Evan C. Rosenberg (NYU: New York University)H-Index: 4
#2Jay Louik (NYU: New York University)H-Index: 3
Last. Daniel Freidman (NYU: New York University)H-Index: 33
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Summary Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD. Results from car...
26 CitationsSource
#1Orrin Devinsky (NYU: New York University)H-Index: 82
#2Jh Cross (UCL: University College London)H-Index: 46
Last. Stephen Wright (GW Pharmaceuticals)H-Index: 11
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BackgroundThe Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome. MethodsIn this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or p...
261 CitationsSource
#1Anastasia S. Suraev (USYD: University of Sydney)H-Index: 8
#2Lisa ToddH-Index: 3
Last. Nicholas Lintzeris (USYD: University of Sydney)H-Index: 30
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Abstract Epilepsy Action Australia conducted an Australian nationwide online survey seeking opinions on and experiences with the use of cannabis-based products for the treatment of epilepsy. The survey was promoted via the Epilepsy Action Australia's main website, on their Facebook page, and by word of mouth. The survey consisted of 39 questions assessing demographics, clinical factors, including diagnosis and seizure types, and experiences with and opinions towards cannabis use in epilepsy. A t...
17 CitationsSource
#2David GlossH-Index: 1
Last. Orrin DevinskyH-Index: 82
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Abstract Treatment-resistant epilepsy (TRE) affects 30% of epilepsy patients and is associated with severe morbidity and increased mortality. Cannabis-based therapies have been used to treat epilepsy for millennia, but only in the last few years have we begun to collect data from adequately powered placebo-controlled, randomized trials (RCTs) with cannabidiol (CBD), a cannabis derivative. Previously, information was limited to case reports, small series, and surveys reporting on the use of CBD a...
52 CitationsSource
#1Dustin SulakH-Index: 1
#2Russell P. Saneto (Seattle Children's)H-Index: 26
Last. Bonni GoldsteinH-Index: 1
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Abstract The widespread patient use of artisanal cannabis preparations has preceded quality validation of cannabis use for epilepsy. Neurologists and cannabinoid specialists are increasingly in a position to monitor and guide the use of herbal cannabis in epilepsy patients. We report the retrospective data on efficacy and adverse effects of artisanal cannabis in Patients with medically refractory epilepsy with mixed etiologies in Washington State, California, and Maine. Clinical considerations, ...
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#1Jacqueline S. Gofshteyn (Children's Hospital of Philadelphia)H-Index: 4
#2Angus A. Wilfong (Boston Children's Hospital)H-Index: 19
Last. Eric D. Marsh (UPenn: University of Pennsylvania)H-Index: 25
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Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex...
43 CitationsSource
Structured online surveys were used to explore the experiences of the parents of children with refractory epilepsy using medicinal cannabis in Mexico during September 2016. The surveys, which were completed in full, were reviewed, and 53 cases of children aged between 9 months and 18 years were identified. Of these, 43 cases (82%) were from Mexico and 10 (18%) were from Latin American countries. Of the 43 Mexican cases, the diagnoses were as follows: 20 cases (47%) had Lennox-Gastaut syndrome (L...
9 CitationsSource
#1Lauren Treat (Anschutz Medical Campus)H-Index: 1
#2Kevin E. Chapman (Anschutz Medical Campus)H-Index: 18
Last. Kelly G. Knupp (Anschutz Medical Campus)H-Index: 13
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SummaryObjective Oral cannabis extracts (OCEs) are being used in the treatment of epilepsy with increasing rates in the United States following product legalization; however, no studies demonstrate clear efficacy. We evaluated the duration of use of OCEs as a measure of perceived benefit in a cohort of patients with pediatric epilepsy. Methods Retrospective chart review was performed of children and adolescents who were given OCEs for treatment of epilepsy. Results Of the 119 patients included i...
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#1J. Helen CrossH-Index: 1
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Abstract With the licensing of cannabidiol for drug resistant seizures in Dravet and Lennox Gastaut syndromes in the United states in 2018, interest in the potential for cannabis-based-medicinal products to meet currently unmet needs for people with epilepsy continues to grow. This review summarizes current knowledge and discusses the implications for future research and practice. Both cannabidiol and tetrahydrocannabinol, the main components, have been extensively studied in animal models, with...
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#1Stefania Capra (RPA: Royal Prince Alfred Hospital)
#2Sujita W. Narayan (USYD: University of Sydney)
Last. Asad E. Patanwala (USYD: University of Sydney)H-Index: 20
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WHAT IS KNOWN AND OBJECTIVE: Drug-resistant seizures are life-threatening and contribute to sustained hospitalization. We present the case of a critically ill 28-year-old male with Lennox-Gastaut syndrome who had approximately 30 seizures/day in the intensive care unit. CASE DESCRIPTION: Patient required mechanical ventilation and pharmacologically induced thiopentone coma. He was commenced on cannabidiol and subsequently extubated. He remained seizure-free thereafter on a combination of cannabi...
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#1Marcella Gherzi (UniGe: University of Genoa)H-Index: 1
#2Giulia MilanoH-Index: 4
Last. Giuliana Cangemi (Istituto Giannina Gaslini)H-Index: 13
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Abstract Objectives to evaluate safety and pharmacokinetic parameters (PK) of medical cannabis in add-on for children and young adults with drug-resistant epilepsy. Design, setting ten patients (4 females, 6 males, age 2.5–23.2 years) were enrolled in a prospective open trial with a galenic preparation (decoction) of Italian cannabis (FM2, ratio THC:CBD = 3:5, range THC 5.2-7.2%; CBD 8.2-11.1%). Patients received the first dose in Hospital, progressively augmented by CBD dose titration (from 1 t...
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#2Francisco S. Guimarães (USP: University of São Paulo)H-Index: 1
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Introduction: Recent trials using cannabidiol (CBD) have shown that most acute and prolonged adverse effects of CBD are mild to moderate, with rare serious adverse effects (SAEs). This review focused on analyzing SAEs of CBD and their possible relation to drug-drug interactions.Areas covered: We systematically analyzed the SAEs reported in randomized controlled trials (RCTs) involving the administration of oral CBD for at least one week in both healthy volunteers and clinical samples.Expert opin...
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Epilepsy is a neurological disorder that affects approximately 50 million people worldwide. There is currently no definitive epilepsy cure. However, in recent years, medicinal cannabis has been successfully trialed as an effective treatment for managing epileptic symptoms, but whose mechanisms of action are largely unknown. Lately, there has been a focus on neuroinflammation as an important factor in the pathology of many epileptic disorders. In this literature review, we consider the links that...
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Summary Background Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders. Methods For this systematic review and meta-analysis we searche...
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