“Severe paediatric epilepsies such as CDKL5 Deficiency Disorder (CDD) are extremely debilitating, largely due to the early-onset and refractory nature of the seizures. Existing treatment options are often ineffective and associated with a host of adverse effects, causing those that are affected to seek alternative treatments.
Cannabis based products have attracted significant attention over recent years, primarily driven by reports of miraculous cures and a renewed public preference for ‘natural’ therapies, thus placing intense pressure on health professionals and the government for regulatory change.
This study provides a comprehensive overview of the potential role for cannabis in the treatment of CDD. Key areas discussed include the history, mechanism of action, efficacy and safety of cannabis based preparations as well as the burden related to CDD.
The evidence supports the use of cannabinoids, especially cannabidiol, in similar forms of refractory epilepsy including Dravet and Lennox-Gastaut syndromes. Evidence for cannabinoids specifically in CDD is limited but growing, with multiple anecdotal reports and an open-label trial showing cannabidiol to be associated with a significant reduction in seizure activity.
This review provides the first comprehensive overview of the potential role for cannabis based preparations in the treatment of CDD and provides justification for further clinical and observational research.”
“Patients with Lennox-Gastaut syndrome (LGS) who completed 1 of 2 randomized, double-blind, placebo-controlled trials of add-on cannabidiol (CBD) (GWPCARE3, NCT02224560 or GWPCARE4, NCT02224690) were invited to enroll in an open-label extension (OLE) study evaluating the long-term safety and efficacy of CBD (GWPCARE5, NCT02224573). Herein we present an interim analysis of the safety, efficacy, and patient-reported outcomes from this trial.
Patients received a pharmaceutical formulation of highly purified CBD oral solution (Epidiolex; 100 mg/mL), titrated from 2.5 to 20 mg/kg/d over a 2-week titration period, in addition to their existing medications. Doses could be reduced if not tolerated or increased up to 30 mg/kg/d if thought to be of benefit.
This interim analysis was based on a November 2016 data cut. Of 368 patients who completed treatment in GWPCARE3 and GWPCARE4, 366 (99.5%) enrolled in the OLE study (GWPCARE5). Median treatment duration was 38 weeks at a mean modal dose of 23 mg/kg/d. Most patients (92.1%) experienced adverse events (AEs), primarily of mild (32.5%) or moderate (43.4%) severity. The most common AEs were diarrhea (26.8%), somnolence (23.5%), and convulsion (21.3%). Thirty-five patients (9.6%) discontinued treatment due to AEs. Liver transaminase elevations were reported in 37 patients (10.1%), of whom 29 were receiving concomitant valproic acid; 34 cases resolved spontaneously or with dose modification of CBD or concomitant medication. Median reduction from baseline in drop seizure frequency (quantified monthly over 12-week periods) ranged from 48% to 60% through week 48. Median reduction in monthly total seizure frequency ranged from 48% to 57% across all 12-week periods through week 48. Eighty-eight percent of patients/caregivers reported an improvement in the patient’s overall condition per the Subject/Caregiver Global Impression of Change scale.
In this study, long-term add-on CBD treatment had an acceptable safety profile in patients with LGS and led to sustained reductions in seizures.”
“Medical cannabis may be effective treatment for refractory epilepsy.
It is timely to seek users’ and potential users’ opinions in regard to its place in the management of epilepsy.
People with epilepsy (33/71) and carers (38/71) participated. Fifty-four participants indicated no experience with medical cannabis, although 35, mainly with inadequate response to prescription medicines, were willing to ask for a prescription. Concerns included difficulty accessing cannabis and high cost of this treatment. Tablets/capsules was the most acceptable dosage form for development.
These findings suggest wide interest in trialling medical cannabis in individual cases of refractory epilepsy, despite the developing body of literature and some concerns about cost and procurement.”
“There are hundreds of compounds found in the marijuana plant, each contributing differently to the antiepileptic and psychiatric effects. Cannabidiol (CBD) has the most evidence of antiepileptic efficacy and does not have the psychoactive effects of ∆9 -tetrahydrocannabinol. CBD does not act via cannabinoid receptors and its antiepileptic mechanism of action is unknown. Despite considerable community interest in the use of CBD for paediatric epilepsy, there has been little evidence for its use apart from anecdotal reports, until the last year. Three randomized, placebo-controlled, double-blind trials in Dravet syndrome and Lennox-Gastaut syndrome found that CBD produced a 38% to 41% median reduction in all seizures compared to 13% to 19% on placebo. Similarly, CBD resulted in a 39% to 46% responder rate (50% convulsive or drop-seizure reduction) compared to 14% to 27% on placebo. CBD was well tolerated; however, sedation, diarrhoea, and decreased appetite were frequent. CBD shows similar efficacy to established antiepileptic drugs. WHAT THIS PAPER ADDS: Cannabidiol (CBD) shows similar efficacy in the severe paediatric epilepsies to other antiepileptic drugs. Careful down-titration of benzodiazepines is essential to minimize sedation with adjunctive CBD.”
“Treatment with a highly purified oral solution of cannabidiol (CBD), derived from the plant Cannabis sativa L., demonstrated some evidence of central nervous system (CNS)-related adverse events in patients enrolled in phase 3 trials for treatment of childhood-onset epilepsy. Cannabidiol was categorized as a Schedule 1 substance by the United States Drug Enforcement Administration; therefore, it was important to test CBD for human abuse potential.
Administration of a therapeutic dose of CBD (750 mg) showed significantly low abuse potential in a highly sensitive population of polydrug users. Although high and supratherapeutic doses of CBD (1500 mg and 4500 mg, respectively) had detectable subjective effects compared with placebo; the effects were significantly lower than those observed with alprazolam and dronabinol.
The majority of adverse events reported during the trial were of mild or moderate severity; no serious adverse events or deaths were reported.”