“Dravet syndrome (severe myoclonic epilepsy of infancy) is characterised by difficult-to-control seizures. Media reports and small clinical trials suggest that cannabidiol, a non-toxic extract of cannabis, can reduce seizure frequency. A recent multicentre randomised controlled trial of 120 children aged 2–18 years with Dravet syndrome supports its efficacy. Over a 14-week period, children taking 20 mg/kg/day of cannabidiol had a 22.8% reduction (95% confidence interval 5.4–41.1) in seizure frequency compared to a 4-week baseline period. Median convulsive frequency fell from 12.4 to 5.9 per month on cannabidiol, while the placebo group had no change from baseline. No attempt was made to measure non-convulsive seizures (e.g. absences). Subjects took a median of three other anti-convulsant drugs during the trial. Adverse effects were common with cannabidiol, particularly somnolence, fatigue, loss of appetite, vomiting and diarrhoea. Eight patients in the cannabidiol group withdrew compared to one in the placebo group. Nevertheless, 62% of caregivers in the cannabidiol group felt the patient’s overall condition had improved, using a validated global score, compared to 34% in the placebo group (P = 0.02). Unfortunately, the high rate of adverse events may have led to widespread loss of caregiver blinding, and the study is relatively short term. Nevertheless, the reduction in seizures is clinically relevant, and further longer-term randomised controlled trials are clearly warranted. ” https://www.ncbi.nlm.nih.gov/pubmed/29314377 http://onlinelibrary.wiley.com/doi/10.1111/jpc.13803/full]]>
Category Archives: Dravet Syndome
Do Cannabinoids Confer Neuroprotection Against Epilepsy? An Overview.
“The data reviewed herein demonstrate that cannabinoids provide neuroprotection against brain excitability. They seem to induce at least partial restoration of neurotransmitter dysfunction, inducing an anticonvulsant effect that may be the biological substrate of the complex neurochemical effects reported in experimental and clinical studies. A large body of data suggests that cannabinoids can be harnessed as antiepileptic agents. Finally, 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 and it might reduce seizure frequency and might have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy.”
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Anticonvulsant Effects of Cannabidiol in Dravet Syndrome
“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. 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. The importance of this study is that, unlike most other antiseizure medication trials, it assesses a treatment in a specific epilepsy syndrome with a known genetic basis. CBD resulted in a significant decrease of convulsive seizures and seizures of all types in Dravet syndrome, a pharmacoresistant epilepsy known to be associated with high mortality rates.” http://epilepsycurrents.org/doi/10.5698/1535-7597.17.5.281?code=amep-site
Cannabinoids for epilepsy: What do we know and where do we go?
“Over the past decade there has been an increasing interest in using cannabinoids to treat a range of epilepsy syndromes following reports of some remarkable responses in individual patients.
The situation is complicated by the fact that these agents do not appear to work via their attachment to endogenous cannabinoid receptors. Their pharmacokinetics are complex, and bioavailability is variable, resulting in difficulty in developing a suitable formulation for oral delivery. Drug interactions also represent another complication in their everyday use.
Nevertheless, recent randomized, placebo-controlled trials with cannabidiol support its efficacy in Dravet and Lennox-Gastaut syndromes.
Further placebo-controlled studies are underway in adults with focal epilepsy using cannabidivarin. The many unanswered questions in the use of cannabinoids to treat epileptic seizures are briefly summarized in the conclusion.”
https://www.ncbi.nlm.nih.gov/pubmed/29214639
http://onlinelibrary.wiley.com/doi/10.1111/epi.13973/abstract
Cannabidiol as a treatment for epilepsy
“Despite an increasing number of anti-epileptic drugs (AEDs), the proportion of drug-resistant cases of epilepsy has remained fairly static at around 30% and the search for new and improved AEDs continues.
Cannabis has been used as a medical treatment for epilepsy for thousands of years; it contains many active compounds, the most important being tetrahydrocannabinol, which has psychoactive properties, and cannabidiol, which does not.
Animal models and clinical data to date have suggested that cannabidiol is more useful in treating epilepsy; there is limited evidence that tetrahydrocannabinol has some pro-convulsant effects in animal models. The mechanism by which cannabidiol exerts its anti-convulsant properties is currently unclear.
Conclusion. The evidence is increasing that cannabidiol is an effective treatment option for childhood onset severe treatment-resistant epilepsies with a tolerable side effect and safety profile. Further evidence is needed before cannabidiol can be considered in more common or adult onset epilepsies. Longer-term safety data for cannabidiol, particularly considering its effects on the developing brain, are also required.”
https://link.springer.com/article/10.1007%2Fs00415-017-8663-0
Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome.
“Worldwide medicinal use of cannabis is rapidly escalating, despite limited evidence of its efficacy from preclinical and clinical studies. Here we show that cannabidiol (CBD) effectively reduced seizures and autistic-like social deficits in a well-validated mouse genetic model of Dravet syndrome (DS), a severe childhood epilepsy disorder caused by loss-of-function mutations in the brain voltage-gated sodium channel NaV1.1.
The duration and severity of thermally induced seizures and the frequency of spontaneous seizures were substantially decreased. Treatment with lower doses of CBD also improved autistic-like social interaction deficits in DS mice.
Phenotypic rescue was associated with restoration of the excitability of inhibitory interneurons in the hippocampal dentate gyrus, an important area for seizure propagation. Reduced excitability of dentate granule neurons in response to strong depolarizing stimuli was also observed.
The beneficial effects of CBD on inhibitory neurotransmission were mimicked and occluded by an antagonist of GPR55, suggesting that therapeutic effects of CBD are mediated through this lipid-activated G protein-coupled receptor.
Our results provide critical preclinical evidence supporting treatment of epilepsy and autistic-like behaviors linked to DS with CBD. We also introduce antagonism of GPR55 as a potential therapeutic approach by illustrating its beneficial effects in DS mice.
Our study provides essential preclinical evidence needed to build a sound scientific basis for increased medicinal use of CBD.”
Cannabidiol reduced frequency of convulsive seizures in drug resistant Dravet syndrome.
“Study design
Design: Multinational double-blinded placebo-controlled trial. Patients randomised in 1:1 ratio to receive cannabidiol or placebo, in addition to stable antiepileptic treatment regime.
Study question
Setting: Twenty-three centres in Europe and USA.
Patients: Patients aged 2 years to 18 years with established diagnosis of Dravet syndrome having at least four convulsive seizures during the 28-day baseline period despite regular antiepileptic medication.
Intervention: Adjunctive cannabidiol or placebo oral solution at 20 mg per kilogram of body weight per day.
Primary outcome: Percentage change in median frequency of convulsive seizures per month.
Follow-up period: Outcome measured over a 14-week treatment period in comparison to a 4-week baseline period.
Patient follow-up: One hundred and eight (90%) completed the trial: 85% (52/61) in the cannabidiol group and …”
http://ep.bmj.com/content/early/2017/09/22/archdischild-2017-313700
“Epilepsy is one of the world’s oldest recognized and prevalent neurological diseases. It has a great negative impact on patients’ quality of life (QOL) as a consequence of treatment resistant seizures in about 30% of patients together with drugs’ side effects and comorbidities. Therefore, new drugs are needed and