Category Archives: Epilepsy

Successful use of pure cannabidiol for the treatment of super-refractory status epilepticus.

Posted on by
Reply

Epilepsy & Behavior Case Reports

“We present the case of a child with long-standing, super-refractory status epilepticus (SRSE) who manifested prompt and complete resolution of SRSE upon exposure to pure cannabidiol. SRSE emerged in the context of remote suspected encephalitis with previously well-controlled epilepsy. We discuss the extent to which response may be specifically attributed to cannabidiol, with consideration and discussion of multiple potential drug-drug interactions. Based on this case, we propose that adjunctive cannabidiol be considered in the treatment of SRSE.”

https://www.ncbi.nlm.nih.gov/pubmed/30596011

“Adjunctive cannabidiol may be effective in the treatment of super refractory status epilepticus. Given the paucity of evidence-based therapies for SRSE as well as the prompt and enduring response that accompanied the adjunctive administration of CBD in this patient, CBD should be a consideration in the treatment of SRSE.”

https://www.sciencedirect.com/science/article/pii/S2213323218300513?via%3Dihub

Cannabidiol reduces seizures and associated behavioral comorbidities in a range of animal seizure and epilepsy models.

Posted on by
Reply

Epilepsia banner

“Epilepsy is a progressive neurological disease characterized by recurrent seizures and behavioral comorbidities. We investigated the antiseizure effect of cannabidiol (CBD) in a battery of acute seizure models. Additionally, we defined the disease-modifying potential of chronic oral administration of CBD on associated comorbidities in the reduced intensity status epilepticus-spontaneous recurrent seizures (RISE-SRS) model of temporal lobe epilepsy (TLE).

RESULTS:

CBD was effective in a battery of acute seizure models in both mice and rats following intraperitoneal administration. In the pilocarpine-induced status epilepticus rat model, CBD attenuated maximum seizure severity following intravenous administration, further demonstrating CBD’s acute antiseizure efficacy in this rat model. We established that oral CBD attenuated the time-dependent increase in seizure burden and improved TLE-associated motor comorbidities of epileptic rats in the RISE-SRS model without affecting gait. Chronic administration of CBD after the onset of SRS ameliorated reference memory and working memory errors of epileptic animals in a spatial learning and memory task.

SIGNIFICANCE:

The present study illustrates that CBD is a well-tolerated and effective antiseizure agent and illustrates a potential disease-modifying effect of CBD on reducing both seizure burden and associated comorbidities well after the onset of symptomatic seizures in a model of TLE.”

https://www.ncbi.nlm.nih.gov/pubmed/30588604

https://onlinelibrary.wiley.com/doi/full/10.1111/epi.14629

Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial.

Posted on by
Reply

Epilepsia banner

“Add-on cannabidiol (CBD) significantly reduced seizures associated with Dravet syndrome (DS) in a randomized, double-blind, placebo-controlled trial: GWPCARE1 Part B (NCT02091375). Patients who completed GWPCARE1 Part A (NCT02091206) or Part B, or a second placebo-controlled trial, GWPCARE2 (NCT02224703), were invited to enroll in a long-term open-label extension trial, GWPCARE5 (NCT02224573). We present an interim analysis of the safety, efficacy, and patient-reported outcomes from GWPCARE5.

METHODS:

Patients received a pharmaceutical formulation of highly purified CBD in oral solution (100 mg/mL), titrated from 2.5 to 20 mg/kg/d over a 2-week period, with their existing medications. Based on response and tolerance, CBD could be reduced or increased up to 30 mg/kg/d.

RESULTS:

By November 2016, a total of 278 patients had completed the original randomized trials, and 264 (95%) enrolled in this open-label extension. Median treatment duration was 274 days (range 1-512) with a mean modal dose of 21 mg/kg/d, and patients received a median of 3 concomitant antiepileptic medications. Adverse events (AEs) occurred in 93.2% of patients and were mostly mild (36.7%) or moderate (39.0%). Commonly reported AEs were diarrhea (34.5%), pyrexia (27.3%), decreased appetite (25.4%), and somnolence (24.6%). Seventeen patients (6.4%) discontinued due to AEs. Twenty-two of the 128 patients from GWPCARE1 (17.2%), all taking valproic acid, had liver transaminase elevations ≥3 times the upper limit of normal. In patients from GWPCARE1 Part B, the median reduction from baseline in monthly seizure frequency assessed in 12-week periods up to week 48 ranged from 38% to 44% for convulsive seizures and 39% to 51% for total seizures. After 48 weeks of treatment, 85% of patients/caregivers reported improvement in the patient’s overall condition on the Subject/Caregiver Global Impression of Change scale.

SIGNIFICANCE:

This trial shows that long-term CBD treatment had an acceptable safety profile and led to sustained, clinically meaningful reductions in seizure frequency in patients with treatment-resistant DS.”

https://www.ncbi.nlm.nih.gov/pubmed/30582156

https://onlinelibrary.wiley.com/doi/full/10.1111/epi.14628

Cannabis-based products for pediatric epilepsy: A systematic review.

Posted on by
Reply

Epilepsia banner

“Evidence from high-quality randomized controlled trials (RCTs) suggests that cannabidiol probably reduces seizures among children with drug-resistant epilepsy (moderate certainty).”

https://www.ncbi.nlm.nih.gov/pubmed/30515765 

https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.14608

“Phytocannabinoids produce anticonvulsant effects through the endocannabinoid system, with few adverse effects.” https://www.ncbi.nlm.nih.gov/pubmed/25475762

Emerging drugs for the treatment of Dravet syndrome.

Posted on by
Reply

Publication Cover

“Dravet syndrome (DS) is an early-onset genetic developmental epileptic encephalopathy characterized by multiple seizure types which are refractory to antiseizure medication. There is an unmet need for effective and tolerable drugs to control different seizure types in DS types, with the aim of improving quality of life and preventing neurological impairment.

Areas covered: Narrative review of efficacy and tolerability of fenfluramine, cannabidiol (CBD), verapamil and modulators of serotonin signaling pathways (lorcaserin or trazodone) in the treatment of DS.

Expert Opinion/Commentary: A recent large randomized controlled-trial has shown that CBD is effective in the treatment of DS; preliminary data from the placebo-controlled trial on fenfluramine are also promising. Further studies are definitely required to evaluate the role of verapamil and modulators of serotonin signaling in DS. At present, drugs used to treat seizures in DS treat the symptoms of epilepsy rather than its cause(s). Future research should focus on elucidating the natural history of DS and whether appropriate treatment can have a beneficial impact on its disease course. A multidisciplinary, individualized approach to care of DS patients is required.”

https://www.ncbi.nlm.nih.gov/pubmed/30482063

https://www.tandfonline.com/doi/abs/10.1080/14728214.2018.1552937?journalCode=iemd20

The Highs and Lows of the Endocannabinoid System—Another Piece to the Epilepsy Puzzle?

Posted on by
Reply

American Epilepsy Society

“Cannabis extracts have been used for the treatment of epilepsy for centuries.

Yet, until recently, this empirical use was not linked to a known mechanism of action. Of the two main and most frequently investigated compounds derived from the cannabis plant, the mechanism of action of tetrahydrocannabinol (THC) is relatively clear and well documented (via CB1R distributed mainly centrally and CB2R distributed mainly peripherally).

The components of endocannabinoid system (ECS) are omnipresent in our bodies and have very divergent roles. Modulating ECS may have therapeutic potential in many human maladies, including psychiatric disorders (e.g., depression, posttraumatic stress disorder, anxiety, or schizophrenia), neurologic conditions, including epilepsy and neurodegenerative processes, diabetes and its complications, obesity, pain management, cancer treatment, graft versus host disease, treatment of chemotherapy side effects, and so on. The list is long, and it is constantly growing.

We investigated changes in the endocannabinoid system and glucose metabolism during temporal lobe epileptogenesis.

This study provides unique evidence that the CB1R is dynamically and progressively involved from the start of mesial temporal lobe epileptogenesis.”

http://epilepsycurrents.org/doi/10.5698/1535-7597.18.5.315

Long-Term Safety, Tolerability, and Efficacy of Cannabidiol in Children with Refractory Epilepsy: Results from an Expanded Access Program in the US.

Posted on by
Reply

“Purified cannabidiol is a new antiepileptic drug that has recently been approved for use in patients with Lennox-Gastaut and Dravet syndromes, but most published studies have not extended beyond 12-16 weeks.

The objective of this study was to evaluate the long-term safety, tolerability, and efficacy of cannabidiol in children with epilepsy.

 

Twenty-six children were enrolled. Most had genetic epilepsies with daily or weekly seizures and multiple seizure types. All were refractory to prior antiepileptic drugs (range 4-11, mean 7), and were taking two antiepileptic drugs on average. Duration of therapy ranged from 4 to 53 months (mean 21 months). Adverse events were reported in 21 patients (80.8%), including reduced appetite in ten (38.4%), diarrhea in nine (34.6%), and weight loss in eight (30.7%). Four (15.4%) had changes in antiepileptic drug concentrations and three had elevated aspartate aminotransferase and alanine aminotransferase levels when cannabidiol was administered together with valproate. Serious adverse events, reported in six patients (23.1%), included status epilepticus in three, catatonia in two, and hypoalbuminemia in one. Fifteen patients (57.7%) discontinued cannabidiol for lack of efficacy, one because of status epilepticus, and one for severe weight loss. The retention rate declined rapidly in the first 6 months and more gradually thereafter. At 24 months, the number of patients continuing cannabidiol as adjunctive therapy was nine of the original 26 (34.6%). Of these patients, seven (26.9%) had a sustained > 50% reduction in motor seizures, including three (11.5%) who remain seizure free.

CONCLUSION:

Over a 4-year period, cannabidiol was effective in 26.9% of children with otherwise refractory epilepsy. It was well tolerated in about 20% of patients, but 80.8% had adverse events, including 23.1% with serious adverse events. Decreased appetite and diarrhea were frequent along with weight loss that became evident only later in the treatment.”

 https://www.ncbi.nlm.nih.gov/pubmed/30460546
https://link.springer.com/article/10.1007%2Fs40263-018-0589-2

The level of evidence of medical marijuana use for treating disabilities: a scoping review.

Posted on by
Reply

Publication Cover

“There is sufficient evidence that medical marijuana is effective in treating epileptic seizures and chronic pain.

Medical marijuana may improve the level of functioning and quality of life for individuals with certain disabilities.”

https://www.ncbi.nlm.nih.gov/pubmed/30456993

https://www.tandfonline.com/doi/abs/10.1080/09638288.2018.1523952?journalCode=idre20

Cannabis for the treatment of paediatric epilepsy? An update for Canadian paediatricians.

Posted on by
Reply

Issue Cover

“The plant Cannabis sativa produces over 140 known cannabinoids. These chemicals generate considerable interest in the medical research community for their possible application to several intractable disease conditions. Recent reports have prompted parents to strongly consider Cannabis products to treat their children with drug resistant epilepsy. Physicians, though, are reluctant to prescribe Cannabis products due to confusion about their regulatory status and limited clinical data supporting their use. We provide the general paediatrician with a brief review of cannabinoid biology, the literature regarding their use in children with drug resistant epilepsy, the current Health Canada and Canadian Paediatric Society recommendations and also the regulations from the physician regulatory bodies for each province and territory. Given the complexities of conducting research on Cannabis products for children with epilepsy, we also discuss outstanding research objectives that must be addressed to support Cannabis products as an accepted treatment option for children with refractory epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/30455572

https://academic.oup.com/pch/article-abstract/23/6/368/4961446?redirectedFrom=fulltext