Category Archives: Dravet Syndome

[Cannabidiol: its use in refractory epilepsies].

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“Some epileptic syndromes are characterised by seizures that are difficult to control and are associated to delayed neuropsychomotor development, which results in a deterioration in the patient’s quality of life as well as in that of his or her family.

AIM:

To evaluate the use of cannabidiol as adjuvant therapy in patients with refractory epilepsies.

PATIENTS AND METHODS:

An observational study was conducted by means of a survey addressed to the patient’s caregiver. Data collected included information about the patient and the caregiver, changes observed in the seizures, neuropsychological effects, side effects and the family’s overall perception following the use of cannabidiol.

RESULTS:

The evaluation examined 15 patients with refractory epilepsies, who received cannabidiol over a period ranging from one month to one year. The frequency of seizures decreased in 40% of the patients, 60% of the patients were seen to have control over 50% of their seizures and in 27% of them the seizures disappeared completely. Neurocognitive changes were also reported: behaviour improved in 73%; 60% reported an improvement in language; in 50% sleep improved; 43% reported improvements in eating habits; and 100% said their mood had improved. The overall perception of the illness was that there had been improvements in 73% of respondents. The most common side effects were drowsiness and fatigue.

CONCLUSIONS:

These results suggest a possible beneficial effect of cannabidiol on the control of seizures and on the improvement of certain neurocognitive aspects in patients with refractory epilepsies.”

https://www.ncbi.nlm.nih.gov/pubmed/28726233

Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol.

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“Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9-point improvement in overall patient QOLCE (p < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. These differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure-reducing effects; however, further studies in placebo-controlled, double-blind trials are necessary to confirm this finding.”

https://www.ncbi.nlm.nih.gov/pubmed/28617940

http://onlinelibrary.wiley.com/doi/10.1111/epi.13815/abstract

Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome

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“BACKGROUND

The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome.

METHODS

In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment. The primary end point was the change in convulsive-seizure frequency over a 14-week treatment period, as compared with a 4-week baseline period.

RESULTS

The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, −22.8 percentage points; 95% confidence interval [CI], −41.1 to −5.4; P=0.01). The percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). The patient’s overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P=0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group.

CONCLUSIONS

Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375.)”

http://www.nejm.org/doi/10.1056/NEJMoa1611618

“Cannabinoids for Epilepsy — Real Data, at Last”  http://www.nejm.org/doi/full/10.1056/NEJMe1702205

“Cannabidiol (CBD) Significantly Reduces Convulsive Seizure Frequency in Dravet Syndrome (DS): Results of a Multi-center, Randomized, Double-blind, Placebo-controlled Trial (GWPCARE1)” http://files.shareholder.com/downloads/AMDA-1TW341/201889199x0x919787/73B57FA6-CD45-4ABB-8C89-87EFEA36B4ED/1332B_AES_Poster_Dravet_Part_B_.pdf

“EPILEPSY AND MARIJUANA: CANNABIS DRUG REDUCES DRAVET SYNDROME SEIZURES IN LARGE-SCALE CLINICAL TRIAL” http://www.newsweek.com/cannabis-marijuana-dravet-syndrome-epilepsy-clinical-trial-614982

“Study proves medicinal cannabis can help children with severe epilepsy, researchers say” http://www.abc.net.au/news/2017-05-25/scientific-study-medicinal-cannabis-helps-children-with-epilepsy/8556180
 
 
 

Efficacy of Medical Cannabis for Treatment of Refractory Epilepsy in Children and Adolescents with Emphasis on the Israeli Experience.

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“The effectiveness of marijuana in the treatment of epilepsy was originally reported as early as 1800 BC.

There is now concrete evidence to suggest the efficacy of cannabis in the treatment of epilepsy, particularly in the refractory group.

To summarize, in view of the good outcome in a significant number of patients, which is not significantly worse than other accepted options for patients with refractory epilepsy, it seems that medical cannabis should be considered a viable treatment option.”

https://www.ima.org.il/FilesUpload/IMAJ/0/228/114213.pdf

https://www.ima.org.il/imaj/ViewArticle.aspx?aId=4041

https://www.ncbi.nlm.nih.gov/pubmed/28457054

Report from a Survey of Parents Regarding the Use of Cannabidiol (Medicinal cannabis) in Mexican Children with Refractory Epilepsy.

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“Structured online surveys were used to explore the experiences of the parents of children with refractory epilepsy using medicinal cannabis in Mexico during September 2016. The surveys, which were completed in full, were reviewed, and 53 cases of children aged between 9 months and 18 years were identified. Of these, 43 cases (82%) were from Mexico and 10 (18%) were from Latin American countries. Of the 43 Mexican cases, the diagnoses were as follows: 20 cases (47%) had Lennox-Gastaut syndrome (LGS); 13 cases (30%) had unspecified refractory epilepsy (URE); 8 cases (19%) had West syndrome (WS); 1 case (2%) had Doose syndrome (DS); and 1 case (2%) had Ohtahara syndrome (OS). In total, 47.1% of cases had previously been treated with 9 or more anticonvulsant therapies.

The parents reported a decrease in convulsions when cannabidiol was used in 81.3% of the cases; a moderate to significant decrease occurred in 51% of cases, and 16% of cases were free from seizure. The number of antiepileptic drugs being used was reduced in 9/43 (20.9%) cases. No serious adverse effects were reported, with only some mild adverse effects, such as increased appetite or changes in sleep patterns, reported in 42% of cases.”

https://www.ncbi.nlm.nih.gov/pubmed/28392943

Social correlates of health status, quality of life, and mood states in patients treated with cannabidiol for epilepsy.

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“Social characteristics, such as socioeconomic status and race/ethnicity, play a role in the treatment and outcomes of patients with epilepsy (PWE), but little is known about how these factors affect patients receiving cannabidiol (CBD) to treat seizures. This exploratory study examined the sociodemographic profile of patients treated with CBD (n=80) and associations between social factors and patient-centered outcomes – overall health status, Quality of Life in Epilepsy-89 (QOLIE-89), and Profile of Mood States (POMS) – in this population.

Associations were examined using Pearson correlations and multiple ordinary-least-squares regression (alpha=0.1). The sample was predominantly white (96%) and non-Hispanic/Latino (96%); 76% of patients had family incomes of $40,000+/year. Some patients/families reported experiencing food scarcity (13%), not being able to make ends meet (6%), or not being able to afford antiepileptic medications (8%). The patients’ health ratings declined with age and income (p≤0.014), and there was a statistically significant interaction (p<0.055) between these variables: for example, a higher-income 10-year-old had a predicted health rating of 3 (“very good”), followed by a higher-income 40-year-old with a rating of 2 (“good”), a low-income 10-year-old with a rating of 1 (“fair”), and a low-income 40-year-old with a rating of 0 (“poor”).

This is the first study reporting the social profile of patients taking pharmaceutical grade CBD for the treatment of epilepsy. The results suggest that despite free access to this treatment some patients may not be accessing CBD because of their socioeconomic situation or race/ethnicity. Larger, diverse samples and longitudinal data are needed to more accurately model social factors and patient-centered outcomes in PWE receiving CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/28236578

Cannabinoids and epilepsy — Introduction.

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“Over the past five years, the lay press and families of children with catastrophic epilepsies popularized the use of cannabis and cannabinoids to treat seizures. Many state legislatures have responded to the pressure from lay groups and have legalized medical cannabis, which is now available to a majority of people in the United States. Patients throughout the world are also obtaining and using cannabinoids to treat their epilepsy. 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.”  http://www.epilepsybehavior.com/article/S1525-5050(17)30042-2/abstract

http://www.thctotalhealthcare.com/category/epilepsy-2/

Cannabinoids in treatment-resistant epilepsy: A review.

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“Treatment-resistant epilepsy (TRE) affects 30% of epilepsy patients and is associated with severe morbidity and increased mortality.

Cannabis-based therapies have been used to treat epilepsy for millennia, but only in the last few years have we begun to collect data from adequately powered placebo-controlled, randomized trials (RCTs) with cannabidiol (CBD), a cannabis derivative.

Previously, information was limited to case reports, small series, and surveys reporting on the use of CBD and diverse medical marijuana (MMJ) preparations containing: tetrahydrocannabinol (THC), CBD, and many other cannabinoids in differing combinations.

These RCTs have studied the safety and explored the potential efficacy of CBD use in children with Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS).

The role of the placebo response is of paramount importance in studying medical cannabis products given the intense social and traditional media attention, as well as the strong beliefs held by many parents and patients that a natural product is safer and more effective than FDA-approved pharmaceutical agents.

We lack valid data on the safety, efficacy, and dosing of artisanal preparations available from dispensaries in the 25 states and District of Columbia with MMJ programs and online sources of CBD and other cannabinoids. On the other hand, open-label studies with 100mg/ml CBD (Epidiolex®, GW Pharmaceuticals) have provided additional evidence of its efficacy along with an adequate safety profile (including certain drug interactions) in children and young adults with a spectrum of TREs.

Further, Phase 3 RCTs with Epidiolex support efficacy and adequate safety profiles for children with DS and LGS at doses of 10- and 20-mg/kg/day. This article is part of a Special Issue titled “Cannabinoids and Epilepsy”.”

https://www.ncbi.nlm.nih.gov/pubmed/28188044

A case for cannabidiol in Wolf-Hirschhorn syndrome seizure management.

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“Complex, and sometimes intractable, seizures affect the quality of life and cognitive development of over 90% of individuals with Wolf-Hirschhorn syndrome (WHS). Fine resolution genotype-phenotype mapping of the WHS locus recently identified a candidate gene whose probable function has led to insights into a mechanism connecting WHS seizures with those of Dravet syndrome, a distinct condition caused by mutations in SCN1A and SCN1B. In addition to this possible molecular mechanistic connection, these disorders’ seizures share a strikingly similar constellation of features, including clinical presentation, seizure types, early age of onset, EEG pattern, and responses to specific anti-epileptic drugs. Based in part on these similarities, we suggest that a highly successful Phase III clinical trial of a formulation of cannabidiol for Dravet syndrome seizures may be directly translatable into possible benefits for WHS individuals with challenging seizure patterns.”

https://www.ncbi.nlm.nih.gov/pubmed/28102593

Pharmacology of cannabinoids in the treatment of epilepsy.

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“The use of cannabis products in the treatment of epilepsy has long been of interest to researchers and clinicians alike; however, until recently very little published data were available to support its use.

This article summarizes the available scientific data of pharmacology from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including ∆9-tetrahydrocannabinol (∆9-THC), cannabidiol (CBD), ∆9-tetrahydrocannabivarin (∆9-THCV), cannabidivarin (CBDV), and ∆9-tetrahydrocannabinolic acid (Δ9-THCA).

It has long been known that ∆9-THC has partial agonist activity at the endocannabinoid receptors CB1 and CB2, though it also binds to other targets which may modulate neuronal excitability and neuroinflammation.

The actions of Δ9-THCV and Δ9-THCA are less well understood. In contrast to ∆9-THC, CBD has low affinity for CB1 and CB2 receptors and other targets have been investigated to explain its anticonvulsant properties including TRPV1, voltage gated potassium and sodium channels, and GPR55, among others.

We describe the absorption, distribution, metabolism, and excretion of each of the above mentioned compounds. Cannabinoids as a whole are very lipophilic, resulting in decreased bioavailability, which presents challenges in optimal drug delivery. Finally, we discuss the limited drug-drug interaction data available on THC and CBD.

As cannabinoids and cannabis-based products are studied for efficacy as anticonvulsants, more investigation is needed regarding the specific targets of action, optimal drug delivery, and potential drug-drug interactions.”

https://www.ncbi.nlm.nih.gov/pubmed/28087250