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
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
Marijuana derivative reduces seizures in people with treatment-resistant epilepsy
New open-label trial of prescription cannabidiol shows overall safety, efficacy
December 23, 2015
Science Daily/NYU Langone Medical Center / New York University School of Medicine
Cannabidiol (CBD), a medical marijuana derivative, was effective in reducing seizure frequency and well-tolerated and safe for most children and young adults enrolled in a year-long study led by epilepsy specialists at NYU Langone Medical Center.
These latest findings provide the first estimates of safety, tolerability and efficacy of prescription CBD in children and adults with severe, highly treatment-resistant epilepsy. Led by Orrin Devinsky, MD, professor of neurology, neurosurgery, and psychiatry and director of the Comprehensive Epilepsy Center at NYU Langone, the study is published in the December 23 issue of Lancet Neurology. While early findings have been released at medical meetings -- including the 2015 American Academy of Neurology conference -- these are the first findings from the trial to be published in a peer-reviewed journal.
The study took place at 11 epilepsy centers across the country. Patients were given the oral CBD treatment Epidiolex over a 12-week treatment period. Results showed a median 36.5 percent reduction in monthly motor seizures, with the median monthly frequency of motor seizures falling from 30 motor seizures a month at the study's start to 15.8 over the 12 weeks. Equally important, CBD was shown to have a sufficient safety profile and was well-tolerated by many patients, despite some isolated adverse events.
"We are very encouraged by our trial results showing that CBD was safe and well-tolerated for most patients, and that seizures dropped significantly," says Devinsky. "But before we raise hopes for families who regularly deal with the devastation of treatment-resistant epilepsy, more research, including further studies through our ongoing randomized controlled trial, are needed to definitively recommend CBD as a treatment to patients with uncontrolled seizures."
How the Research Was Conducted
The study was an open-labeled trial, meaning that both the researchers and participants' families knew they were receiving CBD, a compound in medical marijuana that does not contain psychoactive properties. Between January 15, 2014, and January 15, 2015, 214 patients between 1 and 30 years of age with intractable, or treatment-resistant, epilepsy were enrolled in the trial. Of that cohort, 162 (76 percent) had at least 12 weeks of follow-up after the first dose of CBD and were included in the safety and tolerability analysis. In addition, 137 of the original study cohort (64 percent) were included in the analysis to determine the drug's efficacy.
Patients were given an oral CBD regimen from 2-5 mg/kg per day, with a dose up-titrated until intolerance occurred or to a maximum dose of 25 mg/kg or 50 mg/kg per day, depending on the trial site. Seizures were recorded by parents or caregivers in diaries and reviewed by the study team at each visit.
Lab screenings also were conducted at baseline, and after 4, 8 and 12 weeks of CBD treatment. The study showed variability in responses of individual seizure types to cannabidiol treatment. For example, the median change in total seizures was 34.6 percent , with the greatest reduction occurring in patients with focal and atonic seizures followed by tonic or tonic-clonic seizures. Two patients were free of all seizure types over the entire 12 weeks.
Adverse events were reported among participants, including drowsiness, decreased appetite, diarrhea, fatigue and convulsion. Most were mild to moderate and transient, but 20 patients had serious adverse events related to CBD use -most commonly status epilepticus, or seizures that last too long or too close together. Five patients had to discontinue treatment due to these adverse events.
Devinsky is currently leading a randomized, controlled trial -- considered the gold standard of scientific research -in which CBD or a placebo is randomly assigned to patients to better tease out the drug's effects and better eliminate research bias.
"I empathize with parents who are looking for answers and will try anything to help their children suffering the devastating effects of intractable epilepsy. But we must let the science, and not anecdotal success stories and high media interest, lead this national discussion," cautions Devinsky. "Taking CBD in a controlled medical setting is vastly different from going to a state where medical marijuana is legal and experimenting with dosing and CBD strains."
https://www.sciencedaily.com/releases/2015/12/151223221532.htm
Could cannabis active substance curb seizures? Experts weed through evidence
May 22, 2014
Science Daily/Wiley
The therapeutic potential of medical marijuana and pure cannabidiol (CBD), an active substance in the cannabis plant, for neurologic conditions is highly debated. A series of articles published in Epilepsia, a journal of the International League Against Epilepsy (ILAE), examine the potential use of medical marijuana and CBD in treating severe forms of epilepsy such as Dravet syndrome.
In a case study, Dr. Edward Maa, Chief of the Comprehensive Epilepsy Program at Denver Health in Denver, Colo., details one mother's experience of providing medical marijuana to her child with Dravet syndrome. The adjunct therapy, a strain of cannabis high in CBD and tetrahydrocannabinol (THC) known as Charlotte's Web, was given in conjunction with the patient's antiepileptic drug regimen. The child's seizure frequency was reduced from 50 convulsions per day to 2 to 3 nighttime convulsions per month.
"Colorado is "ground zero" of the medical marijuana debate," says Dr. Maa. "As medical professionals it is important that we further the evidence of whether CBD in cannabis is an effective antiepileptic therapy." Currently, 21 states and the District of Columbia (DC) have legalized marijuana for medical purposes according to GOVERNING magazine.
A counter-point article summarizes current scientific evidence of CBD use in epilepsy and other neurological or psychiatric disorders including anxiety, schizophrenia and addiction. Previous studies found that THC, the primary psychoactive substance and CBD the main non-psychoactive ingredient in cannabis, display anticonvulsive properties in animals. However, this research was conducted in acute animal models and data is limited for chronic recurrent seizures. Recent studies claim medical marijuana with high ratios of CBD to THC are more effective in seizure control, but the data was anecdotal and not well controlled.
"While cannabis has been used to treat epilepsy for centuries, data from double-blind randomized, controlled trials of CBD or THC in epilepsy is lacking," explains Dr. Orrin Devinsky, Director of the Comprehensive Epilepsy Center at NYU Langone Medical Center in New York and Saint Barnabas Institute of Neurology and Neurosurgery in New Jersey. "Randomized controlled studies of CBD in targeted epilepsy groups, such as patients with Dravet or Lennox-Gastaut syndromes, are in the planning stages."
Dr. Maria Roberta Cilio, Director of Research in Pediatric Epilepsy of the Comprehensive Epilepsy Center at UCSF Benioff Children's Hospital in San Francisco, agrees, "There is a critical need for new therapies, especially for childhood-onset treatment-resistant epilepsies that impair quality of life and contribute to learning and behavioral disorders. Rigorous investigation of the safety and efficacy of medical marijuana or individual components such as CBD are necessary for patients with epilepsy before any conclusion is made. "
"There is much interest in the therapeutic potential of medical marijuana and CBD in treating epilepsy," say Drs. Gary Mathern and Astrid Nehlig, Editors-in-Chief of Epilepsia. "We would like your perspective on this important issue and ask that patients, clinicians, and medical professionals visit http://surveys.verticalresponse.com/a/show/1539433/ea840f4206/0 to provide feedback on the use of medical marijuana in epilepsy."
https://www.sciencedaily.com/releases/2014/05/140522074747.htm
Medical marijuana in treatment of certain brain diseases: Experts weigh in
April 28, 2014
Science Daily/American Academy of Neurology (AAN)
A review by the American Academy of Neurology of available scientific research on the use of medical marijuana in brain diseases finds certain forms of medical marijuana can help treat some symptoms of multiple sclerosis (MS), but do not appear to be helpful in treating drug-induced (levodopa) movements in Parkinson's disease. Not enough evidence was found to show if medical marijuana is helpful in treating motor problems in Huntington's disease, tics in Tourette syndrome, cervical dystonia and seizures in epilepsy. The review is published in the April 29, 2014, print issue of Neurology®, the medical journal of the American Academy of Neurology (AAN), and will be presented at the AAN Annual Meeting in Philadelphia, April 26-May 3, 2014, which is the world's largest gathering of neurologists.
"This review by the world's largest association for neurologists is intended to help neurologists and their patients understand the current research on medical marijuana for the treatment of certain brain diseases," said review author Barbara S. Koppel, MD, of New York Medical College in New York and Fellow of the American Academy of Neurology. "The AAN review also highlights the need for more high-quality studies of the long-term efficacy and safety of medical marijuana in the treatment of neurologic diseases."
The AAN review concluded that certain forms of medical marijuana (only in pill or oral spray form) can help treat some symptoms of MS. These include spasticity, certain types of pain (pain related to spasticity, including painful spasms, and painful burning and numbness) and overactive bladder.
Most of the MS studies examined pill or oral spray forms of medical marijuana. There were two studies that examined smoked medical marijuana for treating MS symptoms. However, the studies did not provide enough information to show if smoked medical marijuana is effective. "It's important to note that medical marijuana can worsen thinking and memory problems, and this is a concern since many people with MS suffer from these problems already due to the disease itself," said Koppel.
For Parkinson's disease, the AAN review concluded that medical marijuana in the form of synthetic tetrahydrocannabinol (THC) pills likely does not help relieve abnormal movements that can develop in the late stages of the disease from the drug levodopa, which is the main drug used to treat shaking, stiffness and slowness of movements.
The AAN review also concluded that there is not enough information to show if medical marijuana, including smoked medical marijuana, is safe or effective in these neurologic diseases: • Motor symptoms in Huntington's disease • Tics in Tourette syndrome • Cervical dystonia (abnormal neck movements) • Seizures in epilepsy
There are safety concerns with medical marijuana use. Side effects reported in at least two studies were nausea, increased weakness, behavioral or mood changes, suicidal thoughts or hallucinations, dizziness or fainting symptoms, fatigue, and feelings of intoxication. There was one report of a seizure.
Mood changes and suicidal thoughts are of special concern for people with MS, who are at an increased risk for depression or suicide. The studies showed the risk of serious psychological effects is about 1 percent, or one in every 100 people.
In general, medical marijuana is prescribed as a treatment for use only when standard treatment has not helped.
https://www.sciencedaily.com/releases/2014/04/140428163633.htm