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
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 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
Cannabidiol may help to reduce seizures for people with treatment-resistant form of epilepsy
January 25, 2018
Science Daily/The Lancet
Treatment with a pharmaceutical formulation of cannabidiol alongside other anti-epilepsy treatments helped to reduce the number of drop seizures -- seizures which involve sudden falls due to loss of muscle tone -- in people with Lennox-Gastaut syndrome who did not respond to previous treatment, according to a phase 3 randomised clinical trial published in The Lancet.
Around 1-4% of childhood epilepsy cases are caused by Lennox-Gastaut syndrome -- a lifelong, severe form of epilepsy involving multiple seizure types and cognitive impairment. While there are a range of drug and non-pharmacological treatments (such as ketogenic diet, nerve stimulation, and brain surgery) available, these only help 10% of patients become seizure free.
The 14-week trial reduced the frequency of seizures, but the long-term efficacy and safety of the pharmaceutical formulation of cannabidiol, as well as the drug's interaction with other epilepsy drugs, now needs to be confirmed.
"There is an urgent need for novel treatment options for patients with Lennox-Gastaut syndrome, and we are pleased that our study has potentially found an additional option to add to patients' existing treatment to reduce drop seizures," says lead author Dr Elizabeth Thiele, Massachusetts General Hospital, USA. "Our results suggest that the use of cannabidiol as an add-on therapy with other anti-epilepsy drugs might significantly reduce the frequency of drop seizures in patients with Lennox-Gastaut syndrome, which is positive news for these patients, who often do not respond to treatment."
She notes: "It's important to highlight that the drug used in this trial is a pharmaceutical formulation, and not medical marijuana."
The 14-week trial involved 171 participants aged 2-55 years from the USA, the Netherlands or Poland, who had had a variety of seizures over the past six months (including two or more drop seizures per week during the four week baseline period).
All participants were highly treatment resistant. Before the trial began, participants had not responded to an average of six anti-epilepsy drugs, were taking three anti-epilepsy drugs, and had 73.8 drop seizures every 28 days, on average.
Participants were given a daily dose of a pharmaceutical formulation of cannabidiol (86 people) or placebo (85 people), alongside their usual treatment, for 14 weeks. During this time participants or their caregivers recorded the number and types of seizures each day, as well as medication use and adverse events.
At the end of the trial, drop seizures reduced by 43.9% for the cannabidiol group (from an average of 71.4 drop seizures per month at the start of the trial, to 31.4 per month at the end), compared with a 21.8% reduction for those taking the placebo (from 74.7 seizures per month to 56.3 per month at the end).
Participants in the cannabidiol group also had a greater reduction in their levels of other seizures, and monthly frequency of all seizures decreased by 41.2% (from an average of 144.6 seizures per month at the start of the trial, to 83.8 per month at the end), compared with a 13.7% reduction for the placebo group (from 176.7 seizures per month to 128.7 at the end of the trial).
62% (53/86) participants in the cannabidiol group experienced side effects related to the treatment, compared with 34% (29/85) participants in the placebo group. The most common adverse events in the cannabidiol group were diarrhoea, drowsiness, fever, decreased appetite and vomiting. Serious adverse events were reported in 20 participants in the cannabidiol group, the most common of which were increases in liver enzymes that showed no signs of lasting damage in four participants.
For 61% of participants in the cannabidiol group and 64% in the placebo group, adverse events resolved during the trial. However, some participants withdrew from the study due to side effects (14% [12/86] participants in the cannabidiol group and one participant in the placebo group). These withdrawals included the four participants with temporary liver enzyme elevations, and other participants who experienced multiple other side-effects.
There were no instances of abuse or misuse of the study drug throughout the trial.
The authors note that potential drug interactions between cannabidiol and an epilepsy drug called clobazam need to be explored further. They also note that different doses of cannabidiol should be explored as this study only trialled one dose, and that the long-term efficacy and safety of the treatment needs to be confirmed. The treatment also needs to be tested in a more ethnically diverse group as 90% of participants in this trial were white.
Writing in a linked Comment, Dr Sophia Varadkar, Great Ormond Street Hospital for Children NHS Foundation Trust, UK, says: "After many years without promise of new treatments in Lennox-Gastaut syndrome, this is an exciting time for patients and clinicians. More data and clinical experience of cannabidiol in Lennox-Gastaut syndrome is expected… Clinical trials with cannabidiol are underway in tuberous sclerosis complex… and infantile spasms… and future studies are expected in the other pharmacoresistant epilepsy syndromes."
https://www.sciencedaily.com/releases/2018/01/180125110804.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