CBD and Epilepsy

CBD and Epilepsy

“Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox–Gastaut syndrome, a severe developmental epileptic encephalopathy”
Source: New England Journal of Medicine.org

Medical Marijuana and Epilepsy

CONTENT HIGHLIGHTS
  • Medical marijuana (also called medical cannabis) is whole plant marijuana or chemicals in the plant used for medical purposes.
  • Cannabinoids are substances in medical cannabis that act on cells in the body, including the brain. The two main cannabinoids used in medicine are tetrahydrocannabinol (THC) and cannabidiol (CBD).
  • The FDA recently approved the use of Epidiolex (a plant-based formulation of CBD) to treat seizures for people 2 years of age and older with Dravet syndrome and Lennox-Gastaut syndrome (LGS).
  • Medical cannabis, CBD, and THC all have possible side effects. The most common side effects of CBD included sleepiness, diarrhea, fatigue, and decreased appetite. CBD also interacts with some other seizure medicines.
  • Careful monitoring of CBD is needed.

The use of cannabis to treat epilepsy and other neurological conditions has been studied for a number of years. It has been hotly debated too.

On June 25, 2018, the U.S. Food & Drug Administration (FDA) approved EPIDIOLEX® (cannabidiol, CBD) oral solution for the treatment of seizures associated with two epilepsy syndromes – Lennox-Gastaut syndromeand Dravet syndrome – in people two years of age or older. Epidiolex represents a new medication option for children with these types of epilepsy. It is also the first ever FDA approved medication to treat seizures in Dravet syndrome.

What does FDA approval of Epidiolex (CBD oral solution) mean?

The FDA approval and Drug Enforcement Administration (DEA) scheduling of Epidiolex brings to market the first plant-based drug derived from the cannabis plant in the U.S.

What is medical cannabis?

Cannabis is known by many names – the most common is marijuana. Cannabis is the Latin name used most often by botanists and pharmaceutical companies. The word marijuana usually refers to the leaves and female flowers of the cannabis plant. Medical cannabis is whole plant marijuana or chemicals in the plant used for medical purposes.

Cannabinoids are substances in cannabis that act on cells in the body (called cannabinoid receptors) to cause some effect. Two major ingredients include

  • Tetrahydrocannabinol, or THC, which causes the psychoactive effects of “getting high”
  • Cannabidiol, or CBD, which does not cause psychoactive effects but has shown some positive effects on certain body systems. This is the part that has been effective in reducing seizures in some people with epilepsy.

Does cannabis help seizures?

Early evidence from laboratory studies, anecdotal reports, and small clinical studies over a number of years suggest that cannabidiol (CBD) could potentially help control seizures. Research on CBD has been hard to do and taken time due to federal regulations and limited access to cannabidiol. There are also many financial and time constraints. In recent years, a number of studies have shown the benefit of specific plant-based CBD product in treating specific groups of people with epilepsy who have not responded to traditional therapies.

What do I need to know about hemp?

Hemp is a variety of Cannabis Sativa L. plant historically grown for fibrous materials found in its stalks and seeds. It has been used to make items such as clothing fiber, upholstery, and other household items.

Hemp traditionally contains lower concentrations of THC and higher levels of CBD. Cannabinoids extracted from hemp plants, including CBD, have until recently been classified as marijuana and considered Schedule I substances. Per the DEA, Schedule I substances currently have no accepted medical use and have a high potential for abuse. A federal law* enacted in December 2018, however, reclassifies hemp and hemp-derived CBD as an agricultural commodity and exempts it from the list of Schedule I Drugs.

Despite this change in the classification of hemp and hemp-derived CBD, the only CBD product that has been rigorously studied and approved to be used as a medical therapy for epilepsy is the drug Epidiolex. While more CBD products may come to market in the coming months, it is important to understand that not every CBD product is the same quality or uniform from batch to batch. Any drug or supplement that is being considered for use as a medical treatment should first be discussed with your doctor. The potential for benefit as well as the interaction with other seizure medications and possible side effects require careful review with your doctor.

*The Agriculture and Nutrition Act of 2018 (H.R. 2) legalizes hemp and hemp-derived CBD. The bill changes the definition of hemp to encompass any plant or product derived from the plant that contain less than 0.3% THC by dry weight and classifies them as exempt from the controlled substance restrictions applied to marijuana. The law further amends the Controlled Substances Act to exempt hemp from Schedule I drugs.

What studies exist to support the use of CBD in epilepsy?

Epidiolex (Cannabidiol, CBD)

Studies in the U.S. of Epidiolex (a plant-based CBD formulation) have been ongoing for a number of years. Data from these studies has helped provide evidence that led to the FDA approval of this product on June 25, 2018.

Epidiolex is a purified (> 98% oil-based) CBD extract from the cannabis plant. It is produced by Greenwich Biosciences (the U.S. based company of GW Pharmaceuticals) to give known and consistent amounts in each dose.

Researchers studied this medicine in controlled clinical trials. These studies used a control group with some people taking a placebo while others were given CBD at different doses. Researchers did not know who was getting the placebo and who was getting CBD. These tpyes of studies are called “gold standard” studies.

A summary of the Epidiolex clinical trials is found below:

  • In controlled and uncontrolled trials in people with Lennox-Gastaut syndrome (LGS) and Dravet syndrome, 689 people were treated with Epidiolex (CBD), including 533 people treated for more than 6 months and 391 people treated for more than 1 year.
  • In an expanded access program and other compassionate use programs, 161 people with Dravet syndrome and LGS were treated with Epidiolex, including 109 people treated for more than 6 months.
  • All study participants were taking other seizure medications.
  • In controlled trials, the rate of stopping the medicine due to any side effect was small and happened most in people taking the higher dose of Epidiolex.
  • The most frequent cause of stopping treatment with Epidiolex was a change in liver function.
  • Sleepiness, sedation, and lethargy led to stopping Epidiolex in 3% of people taking the higher dose.
  • The most common side effects were sleepiness, decreased appetite, diarrhea, change in liver function, fatigue, malaise, asthenia (weakness or lack of energy), rash, insomnia, sleep disorder, poor quality sleep, and infections.

CBD Oil For Epilepsy - A Seizure Free Story

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

Date:
May 16, 2018
Source:
NYU Langone Health / NYU School of Medicine
Summary:
Cannabidiol (CBD), a compound derived from the cannabis plant that does not produce a ‘high,’ https://www.nejm.org/doi/full/10.1056/NEJMoa1714631was 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. This study also is the first to offer information on cannabidiol dosing for patients with treatment-resistant epilepsy.

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.

Story Source:

Materials provided by NYU Langone Health / NYU School of MedicineNote: Content may be edited for style and length.


Journal Reference:

  1. Orrin Devinsky, Anup D. Patel, J. Helen Cross, Vicente Villanueva, Elaine C. Wirrell, Michael Privitera, Sam M. Greenwood, Claire Roberts, Daniel Checketts, Kevan E. VanLandingham, Sameer M. Zuberi. Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut SyndromeNew England Journal of Medicine, 2018; 378 (20): 1888 DOI: 10.1056/NEJMoa1714631

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

Date:
May 16, 2018
Source:
NYU Langone Health / NYU School of Medicine
Summary:
Cannabidiol (CBD), a compound derived from the cannabis plant that does not produce a ‘high,’ 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. This study also is the first to offer information on cannabidiol dosing for patients with treatment-resistant epilepsy.

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.

Story Source:

Materials provided by NYU Langone Health / NYU School of MedicineNote: Content may be edited for style and length.


Journal Reference:

  1. Orrin Devinsky, Anup D. Patel, J. Helen Cross, Vicente Villanueva, Elaine C. Wirrell, Michael Privitera, Sam M. Greenwood, Claire Roberts, Daniel Checketts, Kevan E. VanLandingham, Sameer M. Zuberi. Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut SyndromeNew England Journal of Medicine, 2018; 378 (20): 1888 DOI: 10.1056/NEJMoa1714631

ScienceDaily.com

Illustration of an epileptic attack
Illustration of an epileptic attack

Doctor Explains How CBD Helped a Child with Epilepsy

Benefits of CBD for Epilepsy Fades in One-Third of Patients

–But the observation that two-thirds continued to benefit may be a key finding
  • by Judy George, Contributing Writer, MedPage Today

NEW ORLEANS — About one-third of patients who used cannabidiol (CBD) to manage treatment-resistant epilepsy developed tolerance to it, researchers from Israel reported here.

In a study of 92 children and young adults with treatment-resistant seizures who used cannabis oil extract for an average of 19.8 months, tolerance to CBD emerged in 32.6% of patients, reported Shimrit Uliel-Sibony, MD, of Tel Aviv Sourasky Medical Center’s Dana Children’s Hospital, and colleagues at the American Epilepsy Society annual meeting.

“CBD is a good option for children and adults with certain kinds of epilepsy, but as with anti-epileptic drugs, it can become less effective over time and the dose may need to be increased to manage the seizures,” Uliel-Sibony said in statement. While previous research has shown that the effectiveness of cannabinoids can decrease when it is used for pain management and in the treatment of animals with seizures, this is the first large study to show it can occur with humans who use CBD to treat epilepsy, she added.

In the U.S., the FDA has approved a purified, pharmaceutical-grade formulation of cannabidiol (Epidiolex), a chemical component of the Cannabis sativa plant, for children with Lennox-Gastaut and Dravet syndromes. (The current study used a different product.)

In this prospective study, Uliel-Sibony and colleagues followed patients in Tel Aviv, ages 1-37 years (average age 11.8) from 2014 to 2017 with treatment-resistant epilepsy of various etiologies, ranging from Dravet syndrome and Lennox-Gastaut syndrome to epilepsy caused by stroke. All patients subsequently had been treated with one of two strains of CBD-enriched cannabis oil extract that had a 20:1 CBD-to-tetrahydrocannabinol (THC) ratio.

The researchers defined tolerance as either the necessity to increase dose by ≥30% after efficacy declined, or a response reduction of >30%. They saw tolerance in 30 patients, on an average dose of 12.6 mg/kg/day. The mean time until tolerance appeared was 7.3 months (range 1-24 months).

The researchers increased the CBD dose in most patients who developed tolerance; 12 patients achieved their previous response level and 15 did not.

“By definition, most patients with treatment-resistant epilepsy do not enjoy long-term benefits from a new anti-seizure therapy — that is, a ‘honeymoon effect,'” said Orrin Devinsky, MD, of New York University Langone Health in New York City, who was not involved with the study.

“This study found that tolerance develops in one-third of patients with treatment-resistant epilepsies who showed an initial reduction in seizures to a high CBD/low THC product after 7 months,” Devinsky told MedPage Today. “The observation that two-thirds of patients did benefit over a long follow-up period is a key finding.”

There was no statistically significant correlation between patient’s age and tolerance, but patients with shorter epilepsy duration showed a higher tendency to develop tolerance, Uliel-Sibony’s group noted. Predictive factors and mechanisms are unknown, and long-term studies to better characterize the long-term efficacy and safety of CBD are needed, they added.

Stages of a Seizure
Illustrated Stages and phases of a Seizure.

CBD Oil for Epilepsy & Seizures Dr. Jason Tirado

CBD, Cannabis, Medical Cannabis To Treat Epilepsy and Seizures Dr. Dani Gordon, MD

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.