Use of cannabidiol in the treatment of epilepsy: Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex

Abstract

OBJECTIVE:The objective of this systematic review with meta-analysis was to evaluate the efficacy, safety, and short-and long-term tolerability of cannabidiol (CBD), as an adjunct treatment, in children and adults with Dravet syndrome (SD), Lennox-Gataut syndrome (LGS), or tuberous sclerosis complex (TSC), with inadequate control of seizures. METHODS: This systematic review was conducted through a search for scientific evidence in the Mediline/PubMed, Central Cochrane, and ClinicalTrials. gov databases until April 2022. Selected randomized clinical trials (RCTs) that presented the outcomes: reduction in the frequency of seizures and total seizures (all types), number of patients with a response greater than or equal to 50%, change in caregiver global impression of change (CGIC) (improvement ≥1 category on the initial scale), adverse events (AEs), and tolerability to treatment. This review followed Preferred Reporting Items for Systematic reviews and Meta-Analyses. RESULTS: Notably, six RCTs were included, with a total of 1,034 patients with SD, LGS, and TSC, of which 3 were open-label extension RCTs. The meta-analysis of the studies showed that the use of CBD as compared with placebo, in patients with convulsive seizures refractory to the use of medications, reduces the frequency of seizures by 33%; increases the number of patients with a reduction ≥50% in the frequency of seizures by 20%; increases the number of patients with absence of seizures by 3%; improves the clinical impression evaluated by the caregiver or patient (S/CGIC) in 21%; increases total AEs by 12%; increases serious AE by 16%; increases the risk of treatment abandonment by 12%; and increases the number of patients with transaminase elevation (≥3 times the referral) by 15%. CONCLUSIONS: This systematic review, with meta-analysis, supports the use of CBD in the treatment of patients with seizures, originated in DS, LGS, and TSC, who are resistant to the common medications, presenting satisfactory benefits in reducing seizures and tolerable toxicity.

Judicialização de produtos à base de canabidiol no Brasil: uma análise de 2019 a 2022

“…Entre os diagnósticos de epilepsias classificadas, a epilepsia não especificada (CID-10 G40.9), outras epilepsias e síndromes epilépticas generalizadas (CID-10 G40.4) foram as mais frequentes. A prevalência desses diagnósticos pode ser explicada pelo fato de vários estudos terem evidenciado eficácia e segurança do uso do CBD no tratamento dessa doença e do transtorno do espectro autista, apesar de ainda serem necessários ensaios clínicos randomizados, cegos e controlados para esclarecer os efeitos do CBD 4 , 6 , 7 , 8 , 9 , 10 , 23 , 24 , 25 , 26 , 27 , 28 .…”

“…Além disso, existem relatos de uso para o tratamento de pacientes com transtorno de humor e epilepsia 3 , 4 , 5 . Metanálises evidenciaram benefícios satisfatórios do uso do CBD na redução da frequência de convulsões, com toxicidade tolerável, em pacientes com epilepsia de difícil controle como a síndrome de Lennox-Gastaut, síndrome de Dravet e complexo de esclerose tuberosa 6 , 7 , 8 , 9 .…”

“…Apesar disso, os produtos à base de CBD estão sendo utilizados no tratamento de várias condições clínicas 1 , 2 . Ensaios clínicos que investiguem a eficácia para o tratamento da dor, doenças autoimunes, transtornos psiquiátricos e outras condições são necessários antes que o CBD possa ser recomendado para tratamento viável e seguro 6 , 7 , 8 , 9 .…”

Cannabidiol ameliorates mitochondrial disease via PPARγ activation

“…However, these interventions lead to various drug adverse effects, off-target effects, and/or practical concerns, which limit their translational potential. Of note, the use of CBD for clinical applications has gained much attention given its high-benefit-to-risk ratio and lack of psychoactive properties [15][16][17][18][19][20] , the latter being especially important in the context of pediatric diseases such as LS. Therefore, the reported safe CBD profile in other indications 20 in combination with the substantial beneficial effects found in this study point to this cannabinoid as a potential effective treatment for LS patients.…”

Cannabidiol and brain function: current knowledge and future perspectives

“…Also in human clinical trials, the potential of CBD as a therapeutic agent for drug-resistant seizures has recently been investigated. Its effectiveness in childhood epilepsy including, Lennox–Gastaut syndrome and Dravet syndrome has been studied extensively and summarized in recent systematic reviews ( da Silva Rodrigues et al, 2023 ; Silvinato et al, 2022 ). It was concluded that treatment with CBD successfully reduced the frequency of seizures by 33%, supporting the use of CBD in these patient populations.…”