Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence

Abstract

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.PROSPERO registration numberCRD42017055412.

The challenges in providing safe, effective, affordable cannabis‐based medicines for unapproved indications

“…Within the limitations of the small study sizes, these experiences are broadly consistent with the findings of a recent review of the clinical evidence, 5 which found that cannabidiol halved the frequency of seizures in a substantial minority of children with intractable epilepsy. On the basis of this evidence, the United States Food and Drug Administration has approved the use of cannabidiol for treating patients from 2 years of age with Lennox–Gastaut and Dravet syndrome epilepsy 6 .…”

A Review of Human Studies Assessing Cannabidiol's (CBD) Therapeutic Actions and Potential

“…The role of CBD in patients with epilepsy was investigated in 6 randomized trials totaling 555 subjects, 5 of 6 being double blinded and placebo controlled. 31 In a meta-analysis of these trials in 2018, several notable pooled results were found and reported as relative risk (RR with 95%CI). CBD increased the percentage of patients with a ࣙ50% reduction in seizures (n = 2 trials [n = 291]; RR, 1.74 [95%CI, 1.24-2.3]) and those achieving complete seizure freedom (n = 3 trials [n = 306]; RR, 6.17 [95%CI, 1.50-25.32]) vs placebo while increasing health-related quality of life (n = 2 trials [n = 274]; RR, 1.73 [95%CI, 1.33-2.26]).…”

“…It is impossible to tease out the sole impact of CBD, and even so, the statistical heterogeneity for the aforementioned outcomes was very high (I 2 values of 78.2%, 77.3%, and 93.9%, respectively), undercutting confidence in the results. 31 Two of the randomized trials included in this metaanalysis greatly influenced the results and deserve special mention. They both utilized the Epidiolex version of CBD.…”

Are patients taking pot luck with cannabis?

“…11 But there's no doubt that the 20% to 30% of people who are resistant to conventional antiepileptic drugs require other therapeutic options. 12 Shelley Wagstaff, Advice and Information Services Manager at Epilepsy Action, notes that there is a particular need for new approaches to manage severe paediatric epilepsies.…”

“…In the observational studies, 48.5% of patients showed at least a 50% reduction in seizure frequency, while 8.5% were seizure free. 12 • Anorexia • Chronic motion sickness Moreover, parents, patients and carers were 73% more likely say that the overall condition had improved in the cannabidiol group than with placebo. Indeed, 55.8% of patients in the observational studies reported enhanced quality of life when using cannabinoids.…”