“Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy.
Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL).
Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5-55 years).
Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17).
CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs.
Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.”
https://www.ncbi.nlm.nih.gov/pubmed/29511052
http://jnnp.bmj.com/content/early/2018/02/05/jnnp-2017-317168
Category Archives: Lennox-Gastaut
Cannabidiol Regulates Long Term Potentiation Following Status Epilepticus: Mediation by Calcium Stores and Serotonin.
“Epilepsy is a devastating disease, with cognitive and emotional consequences that are not curable.
In recent years, it became apparent that cannabinoids help patients to cope with epilepsy.
We have studied the effects of cannabidiol (CBD) on the ability to produce long term potentiation (LTP) in stratum radiatum of CA1 region of the mouse hippocampus.
Exposure to seizure-producing pilocarpine reduced the ability to generate LTP in the slice.
Pre-exposure to CBD prevented this effect of pilocarpine.
Furthermore, CBD caused a marked increase in ability to generate LTP, an effect that was blocked by calcium store antagonists as well as by a reduction in serotonin tone. Serotonin, possibly acting at a 5HT1A receptor, or fenfluramine (FFA), which causes release of serotonin from its native terminals, mimicked the effect of CBD.
It is proposed that CBD enhances non-NMDA LTP in the slice by facilitating release of serotonin from terminals, consequently ameliorating the detrimental effects of pilocarpine.”
Cannabis as an anticonvulsant
“There are records of the cannabis plant being used for medicinal purposes in ancient times, and in the 19th century it was used as an effective anti-epileptic drug (AED) in children. However, because of its abuse potential, most countries imposed laws restricting its cultivation and use, and this has greatly inhibited research into possible therapeutic uses. Things are now changing, and cannabis derivatives are now used legally to treat, for example, pain, nausea and spasticity.
The plant contains over 100 biologically active compounds, and recently it has been possible to isolate these and identify the neurochemical mechanisms by which some of them operate: one in particular, cannabidiol”
https://www.ncbi.nlm.nih.gov/pubmed/29449212 http://adc.bmj.com/content/early/2018/02/15/archdischild-2018-314921]]>Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: Practical experiences in a tertiary medical center.
“Medically refractory epilepsy continues to be a challenge worldwide, and despite an increasing number of medical therapies, approximately 1 in 3 patients continues to have seizures.
Cannabidiol (CBD), one of many constituents of the Cannabis sativa or marijuana plant, has received renewed interest in the treatment of epilepsy. While highly purified CBD awaits Food and Drug Administration (FDA) approval, artisanal formulations of CBD are readily available and are seeing increased use in our patient population.
Although randomized controlled trials of CBD are ongoing and promising, data regarding artisanal formulations of CBD are minimal and largely anecdotal. Here, we report a retrospective study to define the efficacy of artisanal CBD preparations in children with epilepsy.
Given the known interaction between CBD and clobazam, we also conducted a subgroup comparison to determine if clobazam use was related to any beneficial effects of CBD. Additionally, we compared response rates with CBD and with clobazam alone within an overlapping patient cohort. A pediatric cohort with epilepsy of 108 patients was identified through a medical record search for patients using CBD oil.
The addition of CBD resulted in 39% of patients having a >50% reduction in seizures, with 10% becoming seizure-free. The responder rate for clobazam was similar. No patients achieved CBD monotherapy, although the weaning of other antiepileptic drugs (AEDs) became possible in 22% of patients. A comparable proportion had AED additions during CBD therapy. With concomitant use of clobazam, 44% of patients had a 50% reduction in seizures upon addition of CBD compared with 33% in the population not taking clobazam; this difference was not statistically significant. The most common reported side effect of CBD was sedation in less than 4% of patients, all of whom were also taking clobazam.
Increased alertness and improved verbal interactions were reported in 14% of patients in the CBD group and 8% of patients in the CBD and clobazam group. Benefits were more marked in the CBD alone group, in contrast to the CBD and clobazam group, but this difference was not statistically significant.
In summary, these findings support efficacy of artisanal CBD preparations in seizure reduction with few significant side effects. The response to CBD was independent of concurrent clobazam use, although clobazam may contribute to the sedation seen with concurrent CBD use.”
“In this retrospective study, we report that artisanal CBD is helpful in the treatment of medically refractory seizures.”
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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 
