Medical marijuana liquid extract may bring hope for children with severe epilepsy
April 13, 2015
Science Daily/American Academy of Neurology (AAN)
A medicinal liquid form of marijuana may show promise as a treatment for children with severe epilepsy that is not responding to other treatments, according to a study released today that will be presented at the American Academy of Neurology's 67th Annual Meeting in Washington, DC, April 18 to 25, 2015.
The study involved 213 people, ranging from toddlers to adults, with a median age of 11 who had severe epilepsy that did not respond to other treatments. Participants had Dravet syndrome and Lennox-Gastaut syndrome, epilepsy types that can lead to intellectual disability and lifelong seizures, as well as 10 other types of severe epilepsy.
The participants were given the drug cannabidiol, a component of marijuana that does not include the psychoactive part of the plant that creates a "high." The drug is a liquid taken daily by mouth. Participants all knew they were receiving the drug in the open-label study, which was designed to determine whether the drug was safe and tolerated well.
Researchers also measured the number of seizures participants had while taking the drug. For the 137 people who completed the 12-week study, the number of seizures decreased by an average of 54 percent from the beginning of the study to the end. Among the 23 people with Dravet syndrome who finished the study, the number of convulsive seizures had gone down by 53 percent by the end of the study. For the 11 people with Lennox-Gastaut syndrome who finished the study, there was a 55 percent reduction in the number of atonic seizures, which cause a sudden loss of muscle tone.
A total of 12 people, or 6 percent, stopped taking the drug due to side effects. Side effects that occurred in more than 10 percent of participants included drowsiness (21 percent), diarrhea (17 percent), tiredness (17 percent) and decreased appetite (16 percent).
Study author Orrin Devinsky, MD, of New York University Langone Comprehensive Epilepsy Center and a Fellow of the American Academy of Neurology, said that these are early findings and larger, placebo-controlled, double-blind trials are needed to measure the effectiveness of the drug.
"So far there have been few formal studies on this marijuana extract," Devinsky said. "These results are of great interest, especially for the children and their parents who have been searching for an answer for these debilitating seizures."
https://www.sciencedaily.com/releases/2015/04/150413183743.htm
Cannabidiol significantly reduces seizures in patients with severe form of epilepsy
Study looked at two doses of cannabis-derived medication's effectiveness in Lennox-Gastaut syndrome
May 16, 2018
Science Daily/NYU Langone Health / NYU School of Medicine
Cannabidiol (CBD), a compound derived from the cannabis plant that does not produce a "high" and has been an increasing focus of medical research, was shown in a new large-scale, randomized, controlled trial to significantly reduce the number of dangerous seizures in patients with a severe form of epilepsy called Lennox-Gastaut syndrome.
In the new study comparing two doses of CBD to a placebo, the researchers reported a 41.9 percent reduction in "drop seizures" -- a type of seizure that results in severe loss of muscle control and balance -- in patients taking a 20 mg/kg/d CBD regimen, a 37.2 percent reduction in those on a 10 mg/kg/d CBD regimen, and a 17.2 percent reduction in a group given a placebo.
The phase III trial was led by principal investigator and study first co-author Orrin Devinsky, MD, a professor of neurology, neurosurgery, and psychiatry at NYU School of Medicine and director of NYU Langone's Comprehensive Epilepsy Center, and was published online May 17 in The New England Journal of Medicine.
"This new study adds rigorous evidence of cannabidiol's effectiveness in reducing seizure burden in a severe form of epilepsy and, importantly, is the first study of its kind to offer more information on proper dosing," says Dr. Devinsky. "These are real medications with real side effects, and as providers we need to know all we can about a potential treatment in order to provide safe and effective care to our patients."
The study included an investigational liquid, oral formulation of CBD called Epidiolex. The product is manufactured by GW Pharmaceuticals, which operates in the U.S. as Greenwich Biosciences; GW Pharmaceuticals funded the clinical trial.
Safety of Two CBD Doses Studied
Lennox-Gastaut syndrome is a rare and severe form of epilepsy characterized by frequent drop seizures and severe cognitive impairment. Six medications are approved to treat seizures in patients with the syndrome, but disabling seizures occur in most patients despite these treatments.
Researchers enrolled 225 patients (age 2 to 55) with Lennox-Gastaut syndrome across 30 international sites in a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of two doses of CBD: Seventy-six patients received 20 mg/kg/d CBD, 73 received 10 mg/kg/d CBD, and 76 were given a placebo. All medications were divided into two doses per day for 14 weeks. The number of seizures were monitored beginning four weeks prior to the study for baseline assessment, then tracked throughout the 14-week study period and afterwards for a four-week safety check.
Side effects occurred in 94 per of patients in the 20 mg CBD group, 84 percent in the 10 mg CBD group, and 72 percent of those taking placebo. Side effects were generally reported as mild or moderate in severity and those that occurred in more than 10 percent of patients included: sleepiness, decreased appetite, diarrhea, upper respiratory infection, fever, vomiting, nasopharyngitis, and status epilepticus. Fourteen patients taking CBD experienced dose-related, elevated liver enzymes that were reversible. Seven participants from the CBD group withdrew from the trial due to side effects compared to one participant in the placebo group.
"This landmark study provides data and evidence that Epidiolex can be an effective and safe treatment for seizures seen in patients with Lennox Gastaut Syndrome, a very difficult to control epilepsy syndrome," adds study co-first author, Anup Patel, MD, chief of Neurology at Nationwide Children's Hospital.
A study led by Dr. Devinsky published in last May's New England Journal of Medicine showed a 39 percent drop in seizure frequency in patients with a different rare form of epilepsy, Dravet syndrome. Those findings represented the first large-scale, randomized clinical trial for the compound. Open label CBD studies led by Dr. Devinsky also have shown positive results for treatment-resistant epilepsies.
In April, a U.S. Food and Drug Administration advisory panel unanimously voted to recommend approval of a new drug application for Epidiolex cannabidiol oral solution, following a meeting where researchers, including Dr. Devinsky, presented their findings. The FDA will decide whether to approve the medication in late June.
"While the news gives hope for a new treatment option to the epilepsy community, more research remains imperative to better determine the effects of CBD and other similar cannabis-derived compounds on other forms of the disease and in more dosing regimens," says Dr. Devinsky.
https://www.sciencedaily.com/releases/2018/05/180516172255.htm
Cannabis-based drug reduces seizures in children with treatment-resistant epilepsy
First study to examine the safety, efficacy of cannabidiol for children
January 5, 2016
Science Daily/University of California - San Francisco
Children and young adults with severe forms of epilepsy that does not respond to standard antiepileptic drugs have fewer seizures when treated with purified cannabinoid, according to a multi-center study led by researchers from UCSF Benioff Children's Hospital San Francisco.
"Better treatment for children with uncontrolled seizures is desperately needed," said Maria Roberta Cilio, MD, PhD, senior author and director of research at the UCSF Pediatric Epilepsy Center. "It's important to get seizure control at any age, but in children, uncontrolled seizures may impact brain and neurocognitive development, which can have an extraordinary effect on quality of life and contribute to progressive cognitive impairment."
The researchers evaluated 162 children and young adults across 11 independent epilepsy centers in the U.S. All of the children were treated with Epidiolex, a purified cannabinoid that comes in a liquid form containing no tetrahydrocannabinol (THC), the psychotropic component in cannabis, over a 12-week period. The results showed a median 36.5 percent reduction in monthly motor seizures, with a median monthly frequency of motor seizures falling from 30 motor seizures a month to 15.8 over the course of the 12 week trial.
The study was published in the December 23, 2015 issue of The Lancet Neurology.
The patients in the trial were all between the ages of one and 30 with intractable epilepsies shown to be resistant to many if not all of the antiepileptic treatments, including drugs and a ketogenic diet. This includes children with Dravet syndrome, a rare genetic disorder that manifests in early childhood with frequent, disabling seizures often occurring daily and numbering into the hundreds, as well as profound cognitive and social deficits.
"This trial is pioneering a new treatment for children with the most severe epilepsies, for whom nothing else works," said Cilio. "This is just the first step. This open label study found that CBD both reduces the frequency of seizures and has an adequate safety profile in children and young adults. Randomized controlled trials are the next step to characterize the true efficacy and safety profile of this promising compound."
UCSF Benioff Children's Hospital San Francisco was the first site to ever administer Epidiolex in a child with epilepsy. In April 2013, the drug was given to a patient after obtaining a special approval from the U.S. Food and Drug Administration's Investigational New Drug (IND) program, and results from that initial experience provided the framework for the current study, according to the researchers. A second patient was then enrolled at UCSF in July 2013, and in January 2014 UCSF and other centers started to enroll patients under an expanded access IND.
Produced by the biopharmaceutical company GW Pharmaceuticals, Epidiolex is considered a schedule 1 substance, meaning it has a high potential for abuse, and is closely monitored and restricted by the FDA. GW Pharmaceuticals supplied the cannabidiol for the study, but had no role in the study design, data analysis, data interpretation, writing of the study, or publication submission. The study was also funded by the Epilepsy Therapy Project of the Epilepsy Foundation, and Finding A Cure for Epilepsy and Seizures (FACES).
https://www.sciencedaily.com/releases/2016/01/160105223552.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