Cannabis-based compound may reduce seizures in children with epilepsy
December 5, 2018
Science Daily/Wiley
A recent analysis of published studies indicates that the use of cannabinoids for the treatment of epilepsy in children looks promising.
Interest has been growing in the use of cannabinoids -- the active chemicals in cannabis or marijuana -- for the treatment of epilepsy in children. A recent Epilepsia analysis of relevant published studies indicates that this strategy looks promising.
The analysis included four randomized controlled trials and 19 non-randomized studies, primarily involving cannabidiol, a particular type of cannabinoid that does not have psychoactive effects.
Among randomized controlled trials involving children with severe forms of epilepsy, there was no statistically significant difference between cannabidiol and placebo in terms of freedom from seizures, sleep disruption, or vomiting. There was a statistically significant reduction in the median frequency of monthly seizures with cannabidiol compared with placebo and an increase in number of participants with at least a 50 percent reduction in seizures.
"Although we saw no significant difference in the number of children who became completely seizure free, we that found a significant number of these children achieved a 50 percent or more reduction in seizures. Any reduction in seizures has a striking impact on the lives of these children and their families," said lead author Jesse Elliott, of the University of Ottawa, in Canada. "Research in this area is active, and we expect a dramatic increase in the number of studies over the next few years."
https://www.sciencedaily.com/releases/2018/12/181205093644.htm
Cannabis-based medicine may cut seizures in half for those with tough-to-treat epilepsy
April 18, 2017
Science Daily/American Academy of Neurology
Taking cannabidiol may cut seizures in half for some children and adults with Lennox-Gastaut syndrome (LGS), a severe form of epilepsy, according to new information released today from a large scale controlled clinical study that will be presented at the American Academy of Neurology's 69th Annual Meeting in Boston, April 22 to 28, 2017. Cannabidiol is a molecule from the cannabis plant that does not have the psychoactive properties that create a "high."
Nearly 40 percent of people with LGS, which starts in childhood, had at least a 50 percent reduction in drop seizures when taking a liquid form of cannabidiol compared to 15 percent taking a placebo.
When someone has a drop seizure, their muscle tone changes, causing them to collapse. Children and adults with LGS have multiple kinds of seizures, including drop seizures and tonic-clonic seizures, which involve loss of consciousness and full-body convulsions. The seizures are hard to control and usually do not respond well to medications. Intellectual development is usually impaired in people with LGS.
Although the drop seizures of LGS are often very brief, they frequently lead to injury and trips to the hospital emergency room, so any reduction in drop seizure frequency is a benefit.
"Our study found that cannabidiol shows great promise in that it may reduce seizures that are otherwise difficult to control," said study author Anup Patel, MD, of Nationwide Children's Hospital and The Ohio State University College of Medicine in Columbus and a member of the American Academy of Neurology.
For the randomized, double-blind, placebo-controlled study, researchers followed 225 people with an average age of 16 for 14 weeks. The participants had an average of 85 drop seizures per month, had already tried an average of six epilepsy drugs that did not work for them and were taking an average of three epilepsy drugs during the study.
Participants were given either a higher dose of 20 mg/kg daily cannabidiol, a lower dose of 10 mg/kg daily cannabidiol or placebo as an add-on to their current medications for 14 weeks.
Those taking the higher dose had a 42 percent reduction in drop seizures overall, and for 40 percent, their seizures were reduced by half or more.
Those taking the lower dose had a 37 percent reduction in drop seizures overall, and for 36 percent, seizures were reduced by half or more.
Those taking the placebo had a 17 percent reduction in drop seizures, and for 15 percent, seizures were reduced by half or more.
There were side effects for 94 percent of those taking the higher dose, 84 percent of those taking the lower dose and 72 percent of those taking placebo, but most side effects were reported as mild to moderate. The two most common were decreased appetite and sleepiness.
Those receiving cannabidiol were up to 2.6 times more likely to say their overall condition had improved than those receiving the placebo, with up to 66 percent reporting improvement compared to 44 percent of those receiving the placebo.
"Our results suggest that cannabidiol may be effective for those with Lennox-Gastaut syndrome in treating drop seizures," said Patel. "This is important because this kind of epilepsy is incredibly difficult to treat. While there were more side effects for those taking cannabidiol, they were mostly well-tolerated. I believe that it may become an important new treatment option for these patients."
There is currently a plan to submit a New Drug Application to the FDA later this year.
https://www.sciencedaily.com/releases/2017/04/170418161907.htm
Benefits of medical marijuana for treatment of epilepsy examined
May 24, 2017
Science Daily/Elsevier
Although cannabis had been used for many centuries for treatment of seizure disorders, medical use became prohibited in the 20th century. However, with the loosening of laws regarding medical marijuana, research and clinical use of marijuana-derived substances are increasing. This has prompted the editors of Epilepsy & Behavior to produce a special issue that presents an in-depth assessment of the potential of cannabinoids for the effective treatment of epilepsy. Cannabinoids are components of the cannabis plant.
Guest Editors Jerzy Szaflarski, MD, PhD, Director of the Epilepsy Center, University of Alabama at Birmingham, and Orrin Devinsky, MD, Director, Epilepsy Center, New York University Langone Medical Center, New York, comment that, "There is an enormous dissociation between the widespread use of cannabis-based therapies to treat diverse epilepsies and our understanding about the efficacy and safety of different cannabinoids in treating different epilepsy syndromes." Because much of the political pressure to allow for medical marijuana use came from patients and lay groups, the goal of this special issue is "to evaluate the concerns and gaps in cannabinoid knowledge and medical education, and to create a curriculum as a first step in building a broader Education Roadmap."
This special issue provides an overview for general neurologists and epileptologists, including historical aspects of cannabis use for epilepsy, overview of cannabis botany, general aspects of the endocannabinoid system as it pertains to epilepsy, pharmacology of cannabinoids, available anecdotal and clinical trial data of cannabinoid use for the treatment of epilepsy, safety data, discussion of possible effects of cannabinoids on the brain including neuroimaging data, and the legal aspects of cannabis production, distribution, and use for the treatment of epilepsy.
Raphael Mechoulam, PhD, Head of the School of Pharmacy and Director of the Institute for Drug Research at Hebrew University, provides an insightful historical perspective. He notes that non-psychoactive cannabidiol (CBD) is officially approved for the treatment of intractable pediatric epilepsy in Israel, but it took over 35 years to conduct the studies and obtain the results. "I expect that over the next decade we shall see major advances both in the medical-scientific and the treatment aspects of epilepsy with the help of CBD and related cannabinoids," explains Dr. Mechoulam.
To move a plant-based drug from research studies to clinical use is a particular challenge for pharmaceutical companies. Suman Chandra, PhD, Senior Research Scientist at the University of Mississippi, and co-authors review how the United States and United Kingdom have addressed the problem of securing uniform supplies of medically pure and potent cannabinoids. They review cultivation and processing of marijuana at two institutions with extensive experience, GW Pharmaceuticals in the U.K. and the University of Mississippi in the U.S.
Because both media coverage of cannabis use in epilepsy and inconsistent classification of medical marijuana usage in different U.S. states have short-circuited the rigorous scientific protocols of the U.S. Food and Drug Administration (FDA), quality validation may be lacking. Dustin Sulak, DO, Integr8 Health (Falmouth, ME) and co-investigators review how "artisanal" cannabis preparations, not subject to state regulatory controls, are being used in Washington and California. They also relate four case studies of pediatric epilepsy patients that illustrate the complexities of treatment due to variability of these preparations.
As an example of how interest in medical use of cannabis can be driven by social media and word-of-mouth, Anastasia S. Suraev, The Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, and co-authors surveyed the Australian epilepsy community. This online survey was promoted by Epilepsy Action Australia, a national non-profit organization that provides education and services to people with epilepsy and their families. There were 976 responses, about 60% from adults with epilepsy and the remainder from children with epilepsy. Overall, 14% reported currently using or having previously used cannabis products to treat epilepsy. Of the 389 children with epilepsy included in the survey, 13% had a reported history of cannabis product use for epilepsy. Of these, 71% of parents/guardians rated cannabis products as successful in helping them manage their child's seizures. Furthermore, 51% of parents/guardians reported reduced use of anti-epileptic drugs by their child after commencing use of cannabis products.
Although cannabis is currently legal for medical purposes in half of the states and another seventeen states allow products that are high in cannabidiol (CBD) and low in THC (tetrahydrocannabinol) for medical use, none of these products has been approved by the FDA. Alice Mead, JD, LLM, GW Pharmaceuticals, Inc. (Carlsbad, CA) provides an overview of the legal aspects of cannabis and cannabidiol, including cultivation, manufacture, distribution, and use for medical purposes.
"We hope these articles help stimulate greater understanding and more importantly, stimulate more studies to scientifically define the potential benefits and harms of cannabis-based therapies for epilepsy," note Dr. Szaflarski and Dr. Devinsky. "We need to develop a curriculum to address the rapidly changing scientific and regulatory landscape surrounding the medical use of cannabis and cannabinoids."
The special issue can be found online at: http://www.epilepsybehavior.com/issue/S1525-5050(17)X0007-3
https://www.sciencedaily.com/releases/2017/05/170524131139.htm
Cannabis-based medicine may cut seizures in half for those with tough-to-treat epilepsy
April 18, 2017
Science Daily/American Academy of Neurology
Taking cannabidiol may cut seizures in half for some children and adults with Lennox-Gastaut syndrome (LGS), a severe form of epilepsy, according to new information released today from a large scale controlled clinical study that will be presented at the American Academy of Neurology's 69th Annual Meeting in Boston, April 22 to 28, 2017. Cannabidiol is a molecule from the cannabis plant that does not have the psychoactive properties that create a "high."
Nearly 40 percent of people with LGS, which starts in childhood, had at least a 50 percent reduction in drop seizures when taking a liquid form of cannabidiol compared to 15 percent taking a placebo.
When someone has a drop seizure, their muscle tone changes, causing them to collapse. Children and adults with LGS have multiple kinds of seizures, including drop seizures and tonic-clonic seizures, which involve loss of consciousness and full-body convulsions. The seizures are hard to control and usually do not respond well to medications. Intellectual development is usually impaired in people with LGS.
Although the drop seizures of LGS are often very brief, they frequently lead to injury and trips to the hospital emergency room, so any reduction in drop seizure frequency is a benefit.
"Our study found that cannabidiol shows great promise in that it may reduce seizures that are otherwise difficult to control," said study author Anup Patel, MD, of Nationwide Children's Hospital and The Ohio State University College of Medicine in Columbus and a member of the American Academy of Neurology.
For the randomized, double-blind, placebo-controlled study, researchers followed 225 people with an average age of 16 for 14 weeks. The participants had an average of 85 drop seizures per month, had already tried an average of six epilepsy drugs that did not work for them and were taking an average of three epilepsy drugs during the study.
Participants were given either a higher dose of 20 mg/kg daily cannabidiol, a lower dose of 10 mg/kg daily cannabidiol or placebo as an add-on to their current medications for 14 weeks.
Those taking the higher dose had a 42 percent reduction in drop seizures overall, and for 40 percent, their seizures were reduced by half or more.
Those taking the lower dose had a 37 percent reduction in drop seizures overall, and for 36 percent, seizures were reduced by half or more.
Those taking the placebo had a 17 percent reduction in drop seizures, and for 15 percent, seizures were reduced by half or more.
There were side effects for 94 percent of those taking the higher dose, 84 percent of those taking the lower dose and 72 percent of those taking placebo, but most side effects were reported as mild to moderate. The two most common were decreased appetite and sleepiness.
Those receiving cannabidiol were up to 2.6 times more likely to say their overall condition had improved than those receiving the placebo, with up to 66 percent reporting improvement compared to 44 percent of those receiving the placebo.
"Our results suggest that cannabidiol may be effective for those with Lennox-Gastaut syndrome in treating drop seizures," said Patel. "This is important because this kind of epilepsy is incredibly difficult to treat. While there were more side effects for those taking cannabidiol, they were mostly well-tolerated. I believe that it may become an important new treatment option for these patients."
There is currently a plan to submit a New Drug Application to the FDA later this year.
https://www.sciencedaily.com/releases/2017/04/170418161907.htm
Patient use of cannabis in epilepsy
December 8, 2014
Science Daily/American Epilepsy Society (AES)
Three studies offer new insights into diverse patient experiences with CBD. Despite all the media and legislative attention, there is little scientific evidence about its effectiveness.
There may have been many anecdotal reports about cannabis and its derivative cannabidiol (CBD) in the treatment of people with epilepsy, especially in very young children who have catastrophic forms of epilepsy such as Lennox Gastaut Syndrome (LGS) or Dravet Syndrome (DS). Despite all the media and legislative attention, there is little scientific evidence about its effectiveness. Three studies presented at the American Epilepsy Society's 68th Annual Meeting offer new insights into diverse patient experiences with CBD.
The first of three studies is from Colorado, where much of the nation's attention has been captured by issues surrounding cannabis. The physicians and researchers at Children's Hospital Colorado and the University of Colorado have a unique perspective on CBD given the large number of cases they have treated. In addition to the many children already in their care, these professionals are now caring for many of the patients who have ventured to Colorado in search of cannabis treatment.
Dr. Kevin Chapman, associate professor of pediatrics and neurology at the University of Colorado, and his colleagues conducted a retrospective review of the 58 children and adolescents (average age of 7) with catastrophic forms of epilepsy who were receiving artisanal oral cannabis extracts when they came under the care of the hospital-based team. Chapman's team found that in only one-third of patients did the parents report a seizure reduction of 50% or more, and this did not correlate with an improvement in their electroencephalograms (EEGs). Of the sixteen patients who had baseline EEGs prior to and during treatment with cannabis, only two showed any signs of improvement. The researchers also noted that the response rate did not change with various strains of cannabis. Notably, families who moved to Colorado for CBD treatment were three times as likely to report a reduction greater than 50% than families who were already in Colorado.
Adverse effects occurred in 47% of patients, with increased seizures or new seizures in 21%, somnolence/fatigue in 14%, and rare adverse events of developmental regression in 10% with one patient needing intubation, and one death.
"This substantial gap between the clinical observations and various anecdotal reports highlighted in popular media underscores the desperate need shared by the entire epilepsy community for robust scientific evidence regarding the potential benefit and risks of marijuana in people with epilepsy," said Dr. Chapman.
A second study documents the experiences reported by parents of children with infantile spasms (IS) or LGS who were treated with artisanal CBD-enriched cannabis preparations. Through a survey of 53 parents whose children had IS and/or LGS (n = 53), the UCLA based researchers found that 92% of parents reported a reduction in seizures and 13% reported complete seizure-freedom. The majority of respondents reported using a CBD preparation with a CBD:THC ratio of at least 15:1. Prior to starting CBD, the parents reported that their children (median age for 3.6 years) had typically tried and failed 8 medications prior to CBD. Most patients with IS had failed both hormonal therapy (prednisolone and/or ACTH) and vagabtrin. The median length of other therapies was 6.9 months. The survey participants reported that side effects of treatment were also less than those with other medications. Benefits reported included improvements in sleep, alertness and mood during the CBD treatment.
"Although this study suggests a potential role for CBD in the treatment of IS and LGS, it is important to note that this study does not represent compelling evidence of efficacy or safety," said Raymond Zhou, research associate, UCLA Infantile Spasms Project. "From a methodological standpoint, this study is extraordinarily vulnerable to participation bias and placebo effect as our data is self-reported by parents and did not use objective measures such as EEG. Our hope in presenting this data is to emphasize the need for controlled clinical trials to establish safety and efficacy."
A third study is a single case of a child with Doose Syndrome whose family initiated independent CBD treatment. A child aged 4 experiencing multiple seizure types tried several medications with various and limited benefits. Baseline video EEG showed that the child had at least 10 seizures per day while awake and asleep. Immediately after starting on CBD the child continued to have seizures and Valproic acid levels increased substantially. When the dosage of Valproic acid was reduced the blood level returned to the previous range, and over 4 months seizures disappeared clinically and a repeat EEG was normal in both awake and asleep periods.
"We cannot recommend CBD treatment based on the limited evidence at this time, but do hope that families who independently seek CBD treatment will continue conventional therapies and remain in close contact with their healthcare providers," said Jeffery Gold, MD, Ph.D., Rady Children's Hospital of San Diego. "Establishing EEG measures before and after CBD treatment will provide the best possible insight into the benefits of the treatment. Further, since the effect of CBD treatment on other medications is undetermined, we recommend that physicians work with families to determine if adjustments to other medications are necessary."
https://www.sciencedaily.com/releases/2014/12/141208144146.htm
Effectiveness of cannibidiol in epilepsy: Three studies shed new light
October 14, 2014
Science Daily/American Epilepsy Society (AES)
In advance of the American Epilepsy Society's (AES) Annual Meeting in December, the organization has offered highlights of groundbreaking research being studied at a number of institutions regarding the effectiveness of cannibidiol (CBD) and its derivatives as a viable treatment for people with epilepsy.
The first of three studies (Abstract#1.326) to be presented in full at the Annual Meeting is from Colorado, where much of the nation's attention has been captured by issues surrounding cannabis. The physicians and researchers at Children's Hospital Colorado and the University of Colorado have a unique perspective on CBD given the large number of cases they have treated. In addition to the many children already in their care, these professionals are now caring for many of the patients who have ventured to Colorado in search of cannabis treatment.
Dr. Kevin Chapman, associate professor of pediatrics and neurology at the University of Colorado, and his colleagues conducted a retrospective review of the 58 children and adolescents (average age of 7) who had catastrophic forms of epilepsy and were receiving artisanal oral cannabis extracts when they came under the care of the hospital-based team. Chapman's team found that in only one-third of patients did the parents report a seizure reduction of 50% or more, and this did not correlate with an improvement in their electroencephalograms (EEGs). Of the sixteen patients who had baseline EEGs prior to and during treatment with cannabis, only two showed any signs of improvement. The researchers also noted that the response rate did not change with various strains of cannabis. Notably, families who moved to Colorado for CBD treatment were three times as likely to report a reduction greater than 50% than families who were already in Colorado.
Adverse effects occurred in 47% of patients, with increased seizures or new seizures in 21%, somnolence/fatigue in 14%, and rare adverse events of developmental regression in 10% with one patient needing intubation, and one death.
"This substantial gap between the clinical observations and various anecdotal reports highlighted in popular media underscores the desperate need shared by the entire epilepsy community for robust scientific evidence regarding the potential benefit and risks of marijuana in people with epilepsy," said Dr. Chapman.
Two additional studies that will be featured at the Annual Meeting provide updates on the development of Epidiolex (GW Pharmaceuticals), a purified and formulated form of CBD. The first study (Abstract #3.303) explores initial data from an efficacy and safety study, a precursor to a randomized clinical trial. Twenty-three patients with treatment-resistant epilepsies, especially Dravet Syndrome, with an average age of 10, were enrolled in two sites at New York University and the University of California San Francisco. After establishing a 4-week baseline of frequency, type of seizures and existing antiepileptic drug (AED) regimes, patients received a purified 98% oil-based CBD extract, of known and constant composition at a dose of 5mg/kg/day in addition to their baseline AED regimen. The daily dose was gradually increased until intolerance occurred or a maximum dose of 25 mg/kg/day was achieved. After three months of therapy, 39% of patients had a greater than 50% reduction in seizures with a median reduction of 32%. Seizure freedom occurred in 3/9 Dravet patients and 1/14 patients with other forms of epilepsy. Adverse effects were mostly mild or moderate and included somnolence, fatigue, AED level increases, decreased appetite, weight gain, diarrhea, increased appetite and weight loss.
"These results are encouraging, especially since they involved a group of children and young adults with very treatment-resistant epilepsy. However, we await the planned double-blind study to truly assess the safety and efficacy of Epidiolex," said Orrin Devinsky, M.D., director of the NYU Comprehensive Epilepsy Center and professor of neurology, neurosurgery and psychiatry at the NYU School of Medicine.
The second abstract related to Epidiolex (Abstract #2.309) examined the drug interactions between existing AEDs and the CBD extract Epidiolex. In this study, 33 patients (with an average age of 10) were taking an average of three different AEDs including clobazam (54.5% of patients), valproate (36.4%) and levetiracetam (30.3%), felbamate (21.2%), Lamotrigine (18.2%) and zonisamide (18.2%). Baseline AED concentrations were established and then taken again after the addition of CBD. Patients were given a purified 98% CBD extract, of known and constant composition at a dose of 5mg/kg/day in addition to their baseline AEDs. The study found that in patients on multiple AEDs, the addition of CBD may be associated with changes in serum concentrations of some concomitant AEDs. A subset of patients experienced an increase in clobazam concentrations requiring a dose adjustment and suggesting CBD's effects on the major metabolic pathway of clobazam.
"These results support experimental findings that CBD can affect metabolism of some common anti-epileptic drugs though the effects may not be seen in all patients. More studies are needed to understand the potentially complex interactions between CBD and other drugs but in the meantime, frequent monitoring of drug levels is warranted in children taking CBD-containing products, including medicinal cannabis," Daniel Friedman, M.D., epileptologist and a clinical neurophysiologist at the NYU Comprehensive Epilepsy Center.
https://www.sciencedaily.com/releases/2014/10/141014112710.htm