CBD may alleviate seizures, benefit behaviors in people with neurodevelopmental conditions
September 18, 2019
Science Daily/University of North Carolina Health Care
A marijuana plant extract, also known as cannabidiol (CBD), is being commonly used to improve anxiety, sleep problems, pain, and many other neurological conditions. Now UNC School of Medicine researchers show it may alleviate seizures and normalize brain rhythms in Angelman syndrome, a rare neurodevelopmental condition.
Published in the Journal of Clinical Investigation, the research conducted using Angelman syndrome animal models shows that CBD could benefit kids and adults with this serious condition, which is characterized by intellectual disability, lack of speech, brain rhythm dysfunction, and deleterious and often drug-resistant epilepsy.
"There is an unmet need for better treatments for kids with Angelman syndrome to help them live fuller lives and to aid their families and caregivers," said Ben Philpot, PhD, Kenan Distinguished Professor of Cell Biology and Physiology and associate director of the UNC Neuroscience Center. "Our results show CBD could help the medical community safely meet this need."
CBD, which is a major phytocannabinoid constituent of cannabis, has already shown to have anti-epileptic, anti-anxiety, and anti-psychotic effects. And in 2018, the FDA approved CBD for the treatment of seizures associated with two rare forms of epilepsy, but little is known about the potential anti-seizure and behavioral effects of CBD on Angelman symptom.
The Philpot lab is a leader in the creation of genetically modified mouse models of neurodevelopmental disorders, and they use these models to identify new treatments for various diseases, such as Rett, Pitt-Hopkins, and Angelman syndromes.
In experiments led by first author Bin Gu, PhD, a postdoctoral fellow in the Philpot lab, the UNC-Chapel Hill researchers systematically tested the beneficial effects of CBD on seizures, motor deficits, and brain activity abnormalities -- as measured by EEG -- in mice that genetically model Angelman syndrome, with the expectation that this information could guide eventual clinical use.
The researchers found that a single injection of CBD substantially lessened seizure severity in mice when the seizures were experimentally triggered by elevated body temperature or loud sounds. A typical anti-convulsant dose of CBD (100 mg/kg) caused mild sedation in mice but had little effect on motor coordination or balance. CBD also restored the normal brain rhythms which are commonly impaired in Angelman syndrome.
"We're confident our study provides the preclinical framework necessary to better guide the rational development of CBD as a therapy to help lessen seizures associated with Angelman syndrome and other neurodevelopmental disorders," Gu said.
Philpot and Gu added that patients and families should always seek advice from their physician before taking any CBD products, and that a human clinical trial is needed to fully understand its efficacy and safety.
https://www.sciencedaily.com/releases/2019/09/190918105631.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
Using medical marijuana to stop seizures in kids
February 8, 2016
Science Daily/Texas A&M University
Desperate for relief, parents are taking unusual steps to help children plagued with seizures. The relief, however, comes in a most unlikely form: marijuana.
As many as 30 percent of people with epilepsy -- or about one million Americans -- still have seizures while on Food and Drug Administration (FDA)-approved treatments. It's left many who suffer from uncontrollable seizures -- or their parents, as many of them are children -- turning to medical marijuana and its derivatives in an attempt to take back control of a disease with no cure.
A seizure is an abnormal electrical storm in the brain that causes sudden alteration in consciousness, sensation and behavior that can manifest from an eye flicker to full-body convulsions. People with medication-resistant (also called intractable) epilepsy suffer from consequences of recurrent seizures, which could damage the brain and adversely impact their quality of life. This is commonly observed in children with certain types of devastating pediatric epilepsy, such as Lennox-Gastaut, Doose and Dravet syndromes.
Stories about desperate parents seeking anything to relieve their children's seizures abound, but how much scientific evidence is there for cannabis' effectiveness?
D. Samba Reddy, Ph.D., R.Ph., professor in the Department of Neuroscience and Experimental Therapeutics at the Texas A&M Health Science Center College of Medicine, studies novel therapies for epilepsy. He recently published an article, with co-author Victoria Golub, in the Journal of Pharmacology and Experimental Therapeutics about the current state of research into medical marijuana for treating epilepsy.
"There was a lot of media attention about how medical marijuana is good for epilepsy," said Reddy, who is a fellow of both the American Association of Pharmaceutical Scientists (AAPS) and the American Association for the Advancement of Science (AAAS). "We became interested in finding out whether there was scientific evidence in the literature to support the claims of these people who have seen great benefits."
There are at least 85 active components of the plant colloquially known as marijuana, but two major ones of have been the focus of study: delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the psychoactive component of the plant, while CBD doesn't cause any sort of a "high" and isn't thought to be addictive. Preliminary studies -- largely in animal models -- have shown CBD might have some anti-seizure potential.
Derivatives of marijuana high in CBD (but with negligible amount of THC) might offer some benefit for intractable epilepsy. CBD-enriched products, like Epidiolex and Realm Oil, exist, but their efficacy hasn't been proven and they exist in a sort of legal grey area. Homemade compounds exist, but since they don't go through rigorous best practice manufacturing procedures and haven't been approved by the FDA, it can be difficult for consumers to know exactly what they're getting.
Although THC is known to share the actions of anandamide (from the Indian Sanskrit word "anand" for bliss or happiness), a naturally occurring compound in the brain, the exact mode of anti-seizure action of CBD is unclear. "It is critical to know how CBD controls seizures, so pharmaceutical companies can design novel synthetic compounds for epilepsy that could surpass the hurdles of mixed CBD extracts," said Reddy, who directs an epilepsy research lab at Texas A&M. These compounds might provide the benefits without some of the risks -- or the legal issues -- associated with the marijuana plant.
A standard manufacturing process and clinical trials might help answer some of these questions, but conducting one isn't easy, and there are currently only 19 clinical trials going on to test the use of cannabinoids for epilepsy. For one thing, cannabis is still listed as a Schedule I substance by the federal government, meaning gaining permission to use it in research on human participants is extremely difficult.
Still, change is occurring at the state level. Recreational marijuana use is legal for adults in four states (Alaska, Colorado, Oregon and Washington) and in 23 states and Washington, DC, medical marijuana is allowed. Texas, in a law passed during the last legislative session in 2015, legalized low-THC cannabis oils for people with intractable epilepsy while still prohibiting medical marijuana more broadly.
A new study at the University of Colorado Anschutz Medical Campus is enrolling Dravet epilepsy patients who have tried Charlotte's Web, a specific strain of medical marijuana that is low in THC and high in CBD. The researchers will compare the genetics of those who have seen seizure activity decreased dramatically (at least 50 percent) in response to the drug versus those who did not. Although this research could yield useful information about how CBD and genetic factors interact in a Dravet population, it is not the gold standard of scientific drug trials: the randomized, placebo-controlled, double-blinded clinical trial in which patients were randomly assigned to either CBD or a placebo.
As for experts like Reddy, who is a Texas board-certified pharmacist, most are taking a cautious wait-and-see approach.
The American Epilepsy Society (AES) has released a statement on the use of medical marijuana in the treatment of epilepsy stating that due to the lack of data, no conclusion can be drawn at present.
The Epilepsy Foundation doesn't specifically discourage cannabis use, but urges anyone exploring treatment for epilepsy to work with their treating physician to make the best decisions for their own care and to follow applicable laws.
"Despite all of the controversy about medical marijuana as a potential therapy for epilepsy," Reddy said, "most people agree that what we need is greater rigorous scientific study into cannabinoids to prove or disprove their safety and efficacy."
https://www.sciencedaily.com/releases/2016/02/160208140604.htm