CBD Alleviates Seizures in Animal Model of Angelman Syndrome, a Severe Neurodevelopmental Condition

University of North Carolina School of Medicine researchers show that CBD 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, Ph.D., 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.”

MGC Pharmaceuticals will Study Low THC Formula for Epilepsy Treatment

MGC Pharmaceuticals has received Human Research Ethics Committee approval to conduct a head-to-head clinical study to compare the effectiveness of its low tetrahydrocannabinol formula for the treatment of drug-resistant epilepsy to its 100% cannabidiol product.

The low tetrahydrocannabinol product is a proprietary pharmaceutical-grade phytocannabinoid-derived medicine authorized for prescription as an Investigational Medicinal Product in Australia and the UK, while the 100% cannabidiol product is currently available under Australia’s Special Access Scheme.

Management said the study, which will be carried out together with Cannabis Access Clinics and Epilepsy Action Australia, will be one of the first clinical opportunities in the world to assess and collect several data points.

These data points include the long-term safety of tetrahydrocannabinol treatments, the efficacy of cannabinoid treatments compared to currently available treatments and doctors’ assessments on cannabinoid medicine’s long-term impact on the quality of treatment and quality of life.

MGC said the study would be carried out on 100 patients from Cannabis Access Clinics for 12 months.

MGC Pharma to Test Cannabis Epilepsy Drug on Driving Performance

CannEpil is an approved drug currently being sold in Australia and parts of Europe and South America for the treatment of refractory, drug-resistant epilepsy.

And now the company has received approval from the Human Research Ethics Committee — which must sign off on all clinical trials before they can proceed — to conduct a controlled trial on its effects on driver competency and performance.

Data from the trial, if successful, will then form part of the application to be submitted to the Australian Therapeutic Goods Administration (TGA) and the European Medicines Agency (EMA) for product registration.

It will be one of the first trials globally to assess the impact of medicinal cannabis products on driving competency.

The hope is that it will allow patients taking CannEpil and other similar products to still drive while under treatment. Australian law currently prohibits patients consuming medicinal cannabis from driving.

Study Recommends Physicians and Healthcare Providers Better Educate Patients about Epilepsy and Cannabis

INTRODUCTION: Medical cannabis is increasingly discussed as an alternative treatment option in neurological diseases, e.g. epilepsy. Supporters and opponents base their propositions mostly on subjective estimates, they confuse cannabis in whole versus extracts and botanical versus synthesized.

METHODS: Two hundred seventy five patients with any kind of epilepsy (56% female, 44% seizure free, 91% on medication) answered a survey on the knowledge, expectations, fears, and willingness to be treated with medical cannabis. Data were analyzed with regard to patient characteristics and clinical data from patient files.

RESULTS: Overall, 70.5% of the patients were familiar with the possibility of medical cannabis treatment, 36.7% with its use in epilepsy. A minority of 10.9% gained the information from their physicians. The majority knew about organic compared to synthetic cannabis. The interest in further information is high (71.3%). Regression analysis (explaining 53.8% of the variance) indicated that positive expectations (in the order of relevance) were seizure control, relaxation, mood, and tolerability whereas fears mostly concerned addiction and delirant intoxication. Men showed a greater interest than women.

CONCLUSION: Many epilepsy patients knew about medical cannabis, were interested in this treatment, and wanted more information. Expectations, however, appear to be based on the connotations of the whole substance cannabis with tetrahydrocannabidiol and its commonly known effects. Unfortunately, patients did not get their information from physicians, but mostly by other sources. In order to avoid prejudices and potentially harmful self-medication, physicians and healthcare providers are called to become familiar with the substance and to inform patients adequately.

NICE (UK) Will Not Recommend Medical Cannabis for Epilepsy and Chronic Pain

The UK’s National Institute for Health and Care Excellence (NICE) has said it is currently unable to recommend cannabis-based medical products (CBMPs) for severe treatment-resistant epilepsy.

In draft guidance on the use of CBMPs, NICE said that more research into the use of CBMP for the treatment of a number of conditions was needed because “current research is limited and of low quality”, adding that clinical trials had shown a high level of adverse events.

However, the committee that drew up the guidance did not make any recommendations against the use of CBMPs, because this might restrict further research in the area and “prevent people who are currently apparently benefiting from continuing with their treatment”, NICE said.

European Medicine Agency Panel Backs Cannabis Drug for Severe Epilepsy

The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of cannabidiol oral solution (Epidyolex, GW Pharma) as add-on therapy for seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome in conjunction with clobazam (multiple brands) for patients as young as 2 years.

The US FDA approved GW’s cannabidiol oral solution last year under the trade name Epidiolex, as reported by Medscape Medical News.

The CHMP’s positive opinion is based on results from four randomized, controlled phase 3 trials that included 714 patients with either LGS or Dravet syndrome. Results showed that add-on therapy with the cannabidiol product was more effective than placebo in reducing seizure frequency.

“This is a significant milestone for patients with LGS and Dravet syndrome as there remains a severe unmet medical need for these rare, lifelong forms of epilepsy,” Martin Brodie, MD, president of the International Bureau for Epilepsy, said in a news release from the drugmaker.

Epilepsy Research Findings: July 2019

This month’s edition of epilepsy news features recent research suggesting that inducing a seizure prior to surgery is just as effective for pinpointing the brain region where seizures originate as a spontaneous seizure as a spontaneous seizure. In addition, CURE Post-Traumatic Epilepsy initiative members Dr. Oleskii Shandra and Dr. Stefanie Robel published work indicating that the amount of a certain type of cell may increase in the brain following repeated, mild TBIs, causing epilepsy.

Safety updates on several anti-epileptic drugs were reported, including results showing pregabalin may be associated with increased suicidal behavior and other hazards, and that certain drugs used to treat epilepsy may increase the risk of dementia. Studies also highlight the need for improved counseling for safe and effective contraception for women with epilepsy, and the need for resources for people with epilepsy in low-income countries.

Summaries of all highlighted studies follow below. We have organized the findings into Research and Discoveries and Also Notable.

Research and Discoveries

Inducing Seizures to Stop Seizures
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Causing seizures by stimulating the brain may be a convenient and more cost-effective way to determine the brain region where seizures are originating prior to surgery.

New Research Could Help Predict Seizures Before They Happen
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A new study has found a pattern of molecules that appears in the blood before a seizure happens, which may lead to the development of an early warning system.

Pregabalin Associated with Increased Suicidal Behavior and Other Hazards 
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Gabapentinoids, a class of drugs used to treat epilepsy and other neurological disorders, are associated with an increased risk of suicidal behavior, unintentional overdoses, head/body injuries, and road traffic incidents and offences. Pregabalin was associated with higher hazards of these outcomes than gabapentin.

Study Furthers Understanding of the Development of Epilepsy Following Mild Traumatic Brain Injury (TBI)
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Featuring the work of CURE PTE Initiative members Dr. Oleskii Shandra and Dr. Stefanie Robel

A type of cell in the brain called an “atypical astrocyte” may increase following trauma, causing epilepsy following repeated, mild TBIs, according to a study by Drs. Oleskii Shandra and Stefanie Robel.

Even People with Well-Controlled Epilepsy May Be at Risk for Sudden Death
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Featuring the work of former CURE Grantee Elizabeth Donner

A new study shows the risk of Sudden Unexpected Death in Epilepsy (SUDEP) may apply to individuals whose epilepsy is well-controlled. Previous, smaller studies showed that SUDEP risk was highest among those with severe, difficult-to-treat epilepsy, however, this study suggests a sizeable minority of SUDEP occurred in patients thought to be treatment-responsive or to have benign epilepsies. The study found that SUDEP occurred in people who had not taken their last dose of epilepsy medication, those who were sleep deprived, and those who had not had a seizure in at least a year.

Anticholinergic Drugs May Increase Risk of Dementia 
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A study suggests that the possible link between anticholinergic drugs and an increased risk of dementia is strongest for certain classes of anticholinergic drugs, including antiepileptic drugs such as oxcarbazepine and carbamazepine.

Research into Cannabis Dosage Shows Reduced Seizures in Children with Severe Epilepsy
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Medicinal cannabis oil containing both cannabidiol (CBD) and a small amount of tetrahydrocannabinol (THC) can reduce or end seizures in children with severe, drug-resistant epilepsy, a study by the University of Saskatchewan has found.

Also Notable

The World Health Organization (WHO) Highlights the Scarcity of Treatment for Epilepsy in Low-Income Countries
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Three quarters of people living with epilepsy in low-income countries do not get the treatment they need, increasing their risk of dying prematurely and condemning many to a life of stigma, according to WHO.

Bringing Neuromodulation Therapies to Drug-Resistant Epilepsy Patients
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Researchers at the University of Alabama at Birmingham found that creating an epilepsy neuromodulation clinic improved access for patients and communication with referring physicians, achievement of expected outcomes for reducing or eliminating seizures, and the ability to train future providers in programming neuromodulation devices.

Encoded Therapeutics Gets $104M to Propel ‘Precision Gene Therapy’ for Dravet Syndrome
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Encoded Therapeutics received $104 million to fund a precision gene therapy for Dravet syndrome. The company will also use the funds to advance its preclinical programs and come up with new treatments for severe genetic disorders.

Improved Counseling Needed for Safe, Effective Contraception in Women With Epilepsy
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Over a third of women with epilepsy do not use highly effective contraception, despite the important, negative consequences of unintended pregnancy such as elevated risk of having offspring with congenital malformations. There is a need for more readily available information and counseling on safe and effective contraception for this community.

Seizures, Coma More Common With Synthetic Cannabinoids in Adolescents

Serious neuropsychiatric adverse events in adolescents are far more common with acute synthetic cannabinoid toxicity than with traditional cannabis toxicity, according to a registry study.

“There are dangerous symptoms affecting the neurologic and psychiatric systems from synthetic cannabinoid usage in adolescents,” Dr. Sarah Ann R. Anderson-Burnett from Columbia University Herbert and Florence Irving Medical Center, New York City, told Reuters Health by email. “Adolescent use of synthetic cannabinoids can lead to severe outcomes, such as coma, seizures, and severe agitation, and understanding this toxicity profile is critical to managing these patients.”

Reported poisonings due to synthetic cannabinoids have increased significantly since 2011, and the number of patients across all age groups seeking emergency medical treatment of synthetic cannabinoid (SC) toxicity is 30 times that of cannabis-associated visits.

Dr. Anderson and colleagues used data from the Toxicology Investigators Consortium Case Registry to compare the neuropsychiatric presentation of adolescents to the emergency department after SC exposure versus cannabis exposure.

Research into Cannabis Dosage for Reducing Seizures in Children with Severe Epilepsy

Medicinal cannabis oil containing both cannabidiol (CBD) and a small amount of THC (the drug that can cause intoxication) can reduce or end seizures in children with severe, drug-resistant epilepsy, a study by the University of Saskatchewan (USask) has found.

Children with severe epilepsy also experienced improvements in their quality of life after taking low doses of the medicinal cannabis oil, according to research published in Frontiers in Neurology.

The study tested the effects of medicinal cannabis oil with 95 percent CBD, a chemical which does not create a high, and five percent THC, a substance which can be intoxicating in large enough doses.

Studying an evidence-based scientifically guided dosage regimen, the research team found no evidence of THC intoxication when using CBD-enriched whole plant extracts.

“What makes these results really exciting is it opens up as a treatment option for kids who have failed to respond to traditional medications,” said Dr. Richard Huntsman, a pediatric neurologist who led the study.

Epilepsy Research Findings: June 2019

This month’s round-up of epilepsy news features an announcement about a new antiepileptic rescue medication, NAYZILAM®. This therapy is the first FDA-approved nasal treatment option for people with epilepsy who experience episodes of frequent seizure activity.

We also highlight many research advances, from the discovery of a compound found in fruit and honey which can inhibit seizures to the development of a new drug to treat Dravet syndrome. Research in the cannabidiol (CBD) space has also advanced, with the creation of a synthetic form of CBD which may be easier to purify and does not need to be cultivated from hemp plants.

In more sobering news, reports over the past month show that one-third of epilepsy cases go without appropriate treatment for up to three years following diagnosis. In addition, people with psychogenic nonepileptic seizures (PNES) as well as epileptic seizures may be at a higher risk for sudden unexpected death in epilepsy (SUDEP)during the years immediately following diagnosis with PNES.

Summaries of all highlighted studies follow below. I’ve organized the findings into three categories: Treatment Advances, Research Discoveries, and Also Notable.

Treatment Advances

FDA Approves NAYZILAM® Nasal Spray to Treat Intermittent, Stereotypic Episodes of Frequent Seizure Activity in People Living with Epilepsy in the US
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The FDA has approved a New Drug Application for UCB’s newest antiepileptic drug NAYZILAM® (midazolam) nasal spray. This therapy is a benzodiazepine indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) distinct from a patient’s usual seizure pattern in individuals with epilepsy who are 12 years of age and older.

Study Advances More Effective Laser Ablation and Standard Epilepsy Surgery 
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In the largest study of its kind to date, researchers across 11 centers analyzed data on a relatively new minimally invasive alternative surgery for epilepsy. These researchers discovered changes that could make the procedure more effective in both laser ablation and standard surgery.

Research Discoveries

Brain Network Activity can Improve in Epilepsy Patients after Surgery
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Successful epilepsy surgery can improve brain connectivity similar to patterns seen in people without epilepsy, according to a new study published in the journal Neurosurgery. The study of 15 people with temporal lobe epilepsy is the first to show improvements in brain networks after surgery compared to a group of healthy subjects.

New Drug Could Help Treat Neonatal Seizures
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A new drug that inhibits neonatal seizures in rodent models could open new avenues for epilepsy treatment in human newborns. Researchers have found that gluconate—a small organic compound found in fruit and honey—acts as an anticonvulsant, inhibiting seizures by targeting the activity of channels that control the flow of chloride ions in and out of neonatal neurons.

Research Looks to Halt Stress-Induced Seizures Following Brain Injury
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The likelihood of developing epilepsy increases significantly with a traumatic brain injury. Stress and anxiety increase that likelihood even more dramatically. Researchers have been able to demonstrate that an injured brain responds differently to stress hormones than a healthy brain. The research team showed abnormal electrical activity in the brain tied to these stress-induced seizures and, most importantly, found a way to stop this activity from occurring.

Synthetic Version of Cannabidiol (CBD) Treats Seizures in Rats
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A synthetic, non-intoxicating analogue of CBD was found to be effective for treating seizures in rats. Researchers note the synthetic CBD alternative is easier to purify than a plant extract, eliminates the need to use agricultural land for hemp cultivation, and could avoid legal complications associated with cannabis-related products.

AZD7325 Has Seizure-Protective Effect in Mouse Model of Dravet Syndrome, Study Says
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Treatment with AZD7325, a compound that stimulates an inhibitory receptor in the brain, has a seizure-protective effect in a mouse model of Dravet syndrome. This treatment significantly increased the temperature threshold animals could withstand without experiencing any seizures during a hyperthermia-induced seizure test.

Children’s Brains Reorganize after Epilepsy Surgery to Retain Visual Perception
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Children can keep their full ability to process and understand visual information after brain surgery for severe epilepsy, according to a study funded by the National Eye Institute, part of the National Institutes of Health. This new report from a study of children who underwent epilepsy surgery and suggests that the lasting effects on visual perception can be minimal, even among children who lost tissue in the brain’s visual centers.

One-Third of Epilepsy Cases Go Untreated up to 3 Years After Diagnosis
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A small yet substantial subset of patients with newly diagnosed epilepsy go without appropriate treatment approximately 3 years after diagnosis. This gap in treatment may be increasing the risk for medical events and hospitalization in these patients.

Study Suggests ‘High Risk Period’ for SUDEP for People with Psychogenic Nonepileptic Seizures in Addition to Epileptic Seizures 
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Findings of a recently published study suggest that patients with comorbid epileptic seizures (ES) and Psychogenic Nonepileptic Seizures (PNES) can die from SUDEP and that there may be a high?risk period after the diagnosis of PNES is made. The authors state such patients should be closely monitored and provided with coordinated care of both their epilepsy and psychiatric disorder(s).

Also Notable

Fralin Biomedical Research Institute Neuroscientist Awarded Grant to Study Epilepsy
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Featuring CURE Grantee Dr. Sharon Swanger

Dr. Sharon Swanger of the Fralin Biomedical Research Institute was recently awarded a $1.7 million grant through the National Institute of Neurological Disorders and Stroke to study the role of glutamate receptors in the thalamus – an area of the brain involved in seizure generation. “If we can figure out how each [receptor] subtype functions and modulate select subtypes, then maybe we can target therapies to the circuit where the disease originated while leaving healthy circuits intact,” said Dr. Swanger.

Tool Helps GPs Predict Risk of Seizures in Pregnancy
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Doctors, midwives, and others can use a new risk calculator to identify those pregnant women at high-risk of seizures and to plan early referral for specialist input. The specialist could determine the need for close monitoring in pregnancy, labor, and after birth, and assess antiepileptic drug management, according to new research in PLOS Medicine. The study authors added that the model’s performance is unlikely to vary with the antiepilepsy drug dose management strategy – and that it could save maternal and infant lives.

Development of Epilepsy Prediction Device to Improve Independence for People with Epilepsy
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The University of Sydney’s Faculty of Engineering and Information Technologies is developing a system, NeuroSyd, which aims at real-time monitoring and processing of brain-signals while driving in a group of people living with epilepsy. NeuroSyd will be developed to deliver an early warning of the likelihood of an epileptic seizure.

Pfizer’s Lyrica at Doses 5mg and 10mg Fails Phase 3 Trial in Epilepsy
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Pfizer’s Lyrica has failed to meet its primary endpoint in a phase 3 trial in primary generalized tonic-clonic (PGTC) seizures. The study evaluated two doses of the drug – 5 mg and 10 mg – over a period of 12 weeks. Treatment with the drug did not result in a statistically significant reduction in seizure frequency versus placebo. Another phase 3 trial in May 2018 was successful, showing that a 14 mg dose of Lyrica resulted in a statistically significant reduction in seizure frequency versus placebo.