Artisanal CBD not as effective as pharmaceutical CBD for reducing seizures
February 27, 2020
Science Daily/American Academy of Neurology
Children and teens with epilepsy who were treated with pharmaceutical cannabidiol (CBD) had much better seizure control than those who were treated with artisanal CBD, according to a preliminary study to be presented at the American Academy of Neurology's 72nd Annual Meeting in Toronto, Canada, April 25 to May 1, 2020.
CBD is a cannabis component that relieves stress and anxiety and has anti-seizure properties. It does not produce a "high" like another cannabis component called tetrahydrocannabinol (THC). Pharmaceutical CBD for epilepsy does not have THC. It is FDA approved for use in two severe forms of childhood epilepsy, Dravet syndrome and Lennox-Gastaut syndrome, which do not respond well to other medications. Artisanal CBD is manufactured using varying techniques and contains variable amounts of CBD and THC.
"The use of medical cannabis to treat various medical conditions has grown in recent years. While not always legal, artisanal CBD has been available longer, so some people have been using it to treat epilepsy for years," said study author Nathan T. Cohen, M.D., of Children's National Hospital in Washington D.C., and a member of the American Academy of Neurology. "They may want to reconsider because our research indicates that pharmaceutical CBD may indeed be more effective than artisanal CBD."
For the study, researchers reviewed the medical charts of 31 children and teens with an average age of 10 who were followed for an average age of one year. All had some form of epilepsy including 32% with Lennox-Gastaut syndrome and 6% with Dravet syndrome. Of the group, 22 were taking pharmaceutical CBD and nine were taking artisanal CBD. Researchers recorded medication doses, levels of CBD in the blood, seizure history and reduction in seizures with medication and side effects.
Those taking artisanal CBD had an average level of CBD in the blood of 31 nanograms per milliliter (ng/mL) compared to 124 ng/mL for those taking pharmaceutical CBD.
Researchers found children and teens taking artisanal CBD had a 70% increase in seizures during the study. Those taking prescription CBD had a 39% reduction in seizures.
However, 11 participants reported side effects. All were taking pharmaceutical CBD. Side effects included sleepiness, low appetite, nausea and diarrhea. Six of those participants stopped taking pharmaceutical CBD due to side effects.
"The difference in seizure control is dramatic and is definitely of concern since many people continue to use artisanal CBD," said Cohen. "However, a limitation of our study is that it was small. More research is needed to see if similar results are found in larger groups of people."
Another limitation of the study was that it was a look back at medical records. It did not involve participants who were given either pharmaceutical or artisanal CBD and then followed over time.
https://www.sciencedaily.com/releases/2020/02/200227160545.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
Cannabis-based medicine may reduce seizures for children with difficult-to-treat epilepsy
April 30, 2019
Science Daily/American Academy of Neurology
Taking a pharmaceutical formulation of cannabidiol, a cannabis-based medicine, cut seizures nearly in half for children with a rare and severe type of epilepsy called Dravet syndrome, according to a phase 3 study released today that will be presented at the American Academy of Neurology's 71st Annual Meeting in Philadelphia, May 4 to 10, 2019. Dravet syndrome, which starts in infancy, can lead to intellectual disability and frequent, prolonged seizures. Cannabidiol is derived from marijuana that does not include the psychoactive part of the plant that creates a "high."
"It's exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families," said study author Ian Miller, MD, of Nicklaus Children's Hospital, formerly Miami Children's Hospital, in Florida. "The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with cannabidiol is a major victory."
The study involved 199 children with an average age of 9 who were divided into three groups. One group received 20 milligrams per kilogram (mg/kg) per day of cannabidiol, the second group received 10 mg/kg per day and the third group received a placebo.
Seizures were recorded for four weeks before the treatments were started to establish a baseline. Then the participants received the treatment for 14 weeks. By the end of the study, seizures with convulsions had decreased for those taking the high dose of the drug by 46 percent and by 49 percent for those taking the lower dose of the drug, compared to 27 percent for those taking the placebo.
Total seizures reduced by 47 percent for those in the high dose group, by 56 percent for those in the lower dose group and by 30 percent for those in the placebo group. In the high dose group, 49 percent of the participants had their seizures cut in half or more, compared to 44 percent in the low dose group and 26 percent in the placebo group.
All of the groups reported side effects, with 90 percent of the high dose group, 88 percent of the low dose group and 89 percent of the placebo group. The most common side effects were decreased appetite, diarrhea, sleepiness, fever and fatigue. About 25 percent of those in the high dose group had serious side effects, compared to 20 percent of those in the low dose group and 15 percent of those in the placebo group. Only participants in the high dose group stopped taking the drug due to side effects; that number was 7 percent.
"Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual," Miller said.
https://www.sciencedaily.com/releases/2019/04/190430164219.htm
Pharmaceutical CBD (cannabidiol) shows promise for children with severe epilepsy
Significant seizure reduction in studies using CBD in combination with AEDs
December 7, 2015
Science Daily/American Epilepsy Society
Around the globe there is high interest in the use of cannabidiol (CBD), a type of cannabinoid, for the treatment of people with epilepsy, especially children who have treatment-resistant forms of the disorder such as Lennox-Gastaut Syndrome (LGS) and Dravet Syndrome (DS). Three studies presented at the American Epilepsy Society's 69th Annual Meeting in Philadelphia highlight emerging efficacy and safety data of Epidiolex, a pharmaceutical liquid formulation of cannabidiol, which is currently undergoing U.S. Food and Drug Administration (FDA) authorized Phase 3 pivotal clinical trials in the United States and across the globe by GW Pharmaceuticals. A fourth study highlights possible interactions of CBD with existing anti-epileptic drugs (AEDs) in animal models of seizures.
The largest CBD study presented efficacy and safety data on GW Pharmaceutical's investigational medicine, Epidiolex (cannabidiol) from open-label Expanded Access programs at 16 sites. The study (abstract 3.034) involves 261 people, predominantly children, who have severe epilepsy that had not responded adequately to other treatments. The average age of the participants was 11. Over the course of 12 weeks, the study participants were given Epidiolex in gradually increasing doses. In all cases, Epidiolex was added to current AED treatment regimes. On average, patients were taking approximately three other AEDs. Participants and their families/caregivers recorded the number of seizures prior to taking CBD and during the 12 weeks of treatment. Clinicians also tested hematologic, liver and kidney function as well as AED levels before treatment and then at four, eight and 12 weeks during the study.
After three months of treatment, the frequency of all seizures was reduced by a median of 45 percent in all participants. Almost half (47%) of the participants in the study experienced a 50 percent or greater reduction in seizures and nine percent of patients were seizure-free. Among specific patient populations, DS patients had a 62 percent reduction in seizures and 13 percent were seizure-free. Patients with LGS experienced a 71 percent reduction in atonic seizures.
Adverse events occurred in more than 10 percent of participants with the most common being somnolence, diarrhea and fatigue and led to discontinuation in 4 percent of patients. Thirty-four percent of participants reported serious adverse events of which 5 percent were considered treatment related including altered liver enzymes (n=4), status epilepticus (n=4), diarrhea (n=4) and others. Twelve percent withdrew from the study for lack of efficacy.
"We are pleased to report these promising data on significant numbers of children," said lead author Orrin Devinsky, M.D., of New York University Langone Medical Center's Comprehensive Epilepsy Center. "These data reinforce and support the safety and efficacy we have shared in previous studies. Most importantly it is providing hope to the children and their families who have been living with debilitating seizures."
However, Devinsky cautions that "these results are from an uncontrolled study. Further study is needed before results can be confirmed. Randomized controlled studies are now underway to help us better understand the effectiveness of the drug. We very much look forward to the results from these studies during 2016," he said.
A related study (abstract 2.296) authored by Michael Oldham, M.D., MPH, formerly at the University of California San Francisco (UCSF) and currently at the University of Louisville, explored the long-term efficacy of Epidiolex. This study followed a subset of the first population (n=25) at UCSF Benioff Children's Hospital San Francisco, with an average age of 9, for one year. The patients took CBD in addition to their regular AED regimen. After 12 months, treatment with CBD resulted in a 50 percent reduction in seizures for 10 participants (40%). One participant with DS remained seizure-free. Twelve of the participants discontinued CBD because the treatment did not work for them. One participant suffered a marked increase in seizure frequency due to CBD.
"The CBD as an add-on therapy reduced seizures by half for a third of the patients in the first 12 weeks of the study," Oldham said. "This substantial improvement was maintained by 40 percent of participants for the entire 12-month period showing strong promise that CBD can be effective in controlling seizures."
A third preclinical study (abstract 3.397) explored the anticonvulsant and tolerability profile of CBD in animal models. Using the Anticonvulsant Screening Program (ASP), the researchers used four well-established acute seizure models and found that CBD exerted significant anticonvulsant effects and was well-tolerated in rodents. This study, provided as a free service by the National Institute of Neurological Disorders and Stroke ASP, was conducted at the University of Utah.
A fourth study, led by Misty D. Smith, Ph.D. at the University of Utah (abstract 1.215), explores how CBD interacts with five different AEDs in animal models of seizure. The study helps determine the effects of CBD in combination with common AEDs, including carbamazepine, valproate, levetiracetam, clobazam and lacosamide. The interactions between these drugs could be additive, meaning the drugs work well together; synergistic, meaning the drugs enhance each other's effects; or antagonistic, which occurs when the combination of drugs seems to reduce overall effectiveness.
Smith used isobolographic analysis of three fixed dose ratio combinations of CBD with each AED in order to rapidly assess the effectiveness of each combination against limbic seizure activity. The study found a significant synergistic interaction of CBD with levetiracetam and significant antagonistic interactions with some of the fixed dose-ratio combinations of CBD with clobazam and CBD with carbamazepine.
"By identifying the synergistic, additive or antagonistic interactions between CBD and other ASDs, we are gaining a better understanding of the nature of these interactions. This will help optimize therapeutic safety and efficacy for CBD going forward," said Smith.
https://www.sciencedaily.com/releases/2015/12/151207145856.htm
Medical marijuana for children with developmental and behavioral disorders?
February 5, 2015
Science Daily/Wolters Kluwer Health: Lippincott Williams and Wilkins
As medical marijuana becomes increasingly accepted, there is growing interest in its use for children and adolescents with developmental and behavioral problems such as autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), according to a review in the February Journal of Developmental & Behavioral Pediatrics, the official journal of the Society for Developmental and Behavioral Pediatrics.
That's despite a lack of studies showing any clinical benefit of cannabis for young patients with these disorders -- whereas evidence strongly suggests harmful effects of regular marijuana use in the developing brain. Scott Hadland, MD, MPH, John R. Knight, MD, and Sion Kim Harris, PhD of Boston Children's Hospital write, "Given the current scarcity of data, cannabis cannot be safely recommended for the treatment of developmental or behavioral disorders at this time."
"Children with severe ASD cannot communicate verbally and may relate to the world through loud, repetitive shrieking and hand-flapping that is very disruptive to their families and all those around them," comments Dr Knight, the study's senior author. "So my heart goes out to families who are searching for something, anything to help their child," he continues. "But in using medicinal marijuana they may be trading away their child's future for short-term symptom control."
Known Harmful Effects of Marijuana in Children and Teens...
The review was prompted by rapid changes in US marijuana policy, with marijuana being permitted for medical use in many jurisdictions and legalized in others. "Amidst this political change, patients and families are increasingly asking whether cannabis and its derivatives may have therapeutic utility for a number of conditions, including developmental and behavioral disorders in children and adolescents," according to Dr Knight and colleagues.
They review the important pharmacological properties of cannabis and related compounds, along with data on marijuana use in the population. Adolescents with developmental and behavioral disorders -- especially ADHD -- may be predisposed to early and heavier substance use. Meanwhile, a growing body of evidence links cannabis to "long-term and potentially irreversible physical, neurocognitive, psychiatric, and psychosocial adverse outcomes."
Over time, regular cannabis use by adolescents has been linked to persistent declines in intelligence quotient and increased risk of addiction, major depression, anxiety disorders, and psychotic thinking. The adolescent brain may be uniquely susceptible to the harmful effects of marijuana, reflecting the role of the cannabinoid receptors in normal neurodevelopment. Brain abnormalities in adults who are heavy marijuana users may have their origin in neurodevelopmental changes starting in adolescence.
...With Little Data on Benefits in Developmental or Behavioral Disorders
While cannabis has been proposed to have a broad range of clinical benefits in adults, "At this time, good evidence is almost entirely lacking for its application in pediatric developmental and behavioral conditions," Dr Knight and coauthors write.
"The scant research that we have on adolescent use is alarming enough," says Leonard Rappaport MD, MS, Chief of the Division of Developmental Medicine at Boston Children's Hospital and past president of the Society for Developmental and Behavioral Pediatrics. "But we are really moving into entirely new territory when we consider giving cannabis to children as that has not even been done in neurotypical children, let alone those with developmental or behavioral problems."
And yet, a number of online groups are advocating the use of "medical marijuana" for children with autism, ADHD, and other developmental and behavioral conditions. These groups often cite evidence from animal research, or from a small number of clinical reports, to claim beneficial effects of cannabis in children. Those beneficial effects are likely from cannabidiols, which also benefit children with uncommon forms of epilepsy and have limited euphoric effects; rather than tetrahydrocannabinol (THC), with its strong euphoric and neurotoxic effects.
This movement, coupled with the increased willingness of physicians to prescribe cannabis, "may result in issuing of medical marijuana permits for developmental or behavioral diagnoses for which no data on efficacy, safety, or tolerability exist," the researchers write. They note that if and when studies of cannabis for developmental and behavioral conditions are performed, they will likely use extracts formulations of known dosage -- rather than plant forms of medical marijuana, which vary widely in strength and effects. Dr Knight adds, "We need more research on cannabidiols, and development of products that are high in cannabidiols and low in THC."
Dr Knight and coauthors hope their article will draw attention to the potential harmful effects of marijuana in young people -- as well as lack of evidence on its effects in those with developmental or behavioral disorders. They conclude, "As marijuana policy evolves and as the drug becomes more readily available, it is important that practicing clinicians recognize the long-term health and neuropsychiatric consequences of regular use."
https://www.sciencedaily.com/releases/2015/02/150205122733.htm