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Study register · detail Systematic Review · Epilepsy · 2026

A systematic review of highly purified cannabidiol in developmental and epileptic encephalopathies and complex treatment-resistant epilepsies: Nonseizure outcomes.

Samanta et al. ·Epilepsy research Impact 1.8
No direction reported GRADE High
Samplek = 32 Studien
n = 1.343 Pat.
DesignSystematic Review
Summary

Systematische Review (PRISMA) zu hochgereinigtem CBD bei DEE und komplexer therapieresistenter Epilepsie (außer LGS, Dravet, TSC); k=32 Studien, n=1343 Patient:innen. 31/32 Studien berichteten Verbesserung nicht-anfallsbezogener Outcomes (u. a. Kognition 9/9, Verhalten 7/7, Kommunikation 7/7, Lebensqualität 5/5). Häufigste UAW gastrointestinal: Diarrhö 17-34%, Erbrechen 5-50%, verminderter Appetit 7-20%. Überwiegend Beobachtungsstudien mit moderatem bis hohem Bias-Risiko; narrative Synthese ohne Meta-Analyse.

Confidence in the evidence
High

The highest of four GRADE levels, the effect estimate is very reliable.

Quality profile
Sample size ★★★★★
Blinding —
Effect size —
Citations / year —
Authors
Samanta D, Moore-Ramdin L, Navetta M, Coppola A
DOI 10.1016/j.eplepsyres.2026.107873↗
Design: Systematic Review
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Abstract
Objective: A plant-derived, highly purified cannabidiol (CBD) oral solution (Epidiolex(R) [US]/Epidyolex(R) [EU]) is approved for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC). Improvements in nonseizure outcomes including cognition and behavior have been reported in patients with epilepsy administered CBD. This systematic literature review (SLR) evaluated studies reporting changes in nonseizure outcomes after CBD initiation in patients with developmental and epileptic encephalopathies (DEEs) and complex treatment-resistant epilepsies (TREs) other than LGS, DS, and Tsc. Methods: An SLR was conducted in March 2024 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Embase, Medline, and Cochrane Central Register of Controlled Trials libraries were searched for studies on TREs, CBD, nonseizure outcomes, and adverse events (AEs). Results were narratively summarized. Results: Thirty-two studies comprising 1343 patients were included. Thirty-one studies reported improvement in nonseizure outcomes in >/= 1 patient, including neuropsychiatric function (n = 9/9 studies), cognitive function (n = 9/9), use of concomitant antiseizure medications (n = 7/8), communication (n = 7/7), behavior (n = 7/7), motor function (n = 6/6), healthcare utilization (n = 5/5), quality of life (n = 5/5), global change (n = 4/4), sleep (n = 2/2), and development (n = 2/2). Reported AEs were consistent with the known safety profile of CBD and most commonly gastrointestinal, including diarrhea (17-34%), vomiting (5-50%), and decreased appetite (7-20%). Conclusion: This SLR mainly identified observational studies with moderate to high bias risk. The available evidence suggests CBD may improve various nonseizure outcomes in patients with DEEs and complex TREs, while underscoring the need for rigorous confirmatory studies.
Indication
Further studies on Epilepsy
All studies →
S Devinsky et al. · 2018 · The New England journal of medicine
973 citations
Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome.
Clear benefit RCT

Multizentrische Phase-III-RCT bei Lennox-Gastaut-Syndrom (n=225, Alter 2-55 Jahre, 30 Zentren), Cannabidiol 20 mg/kg vs. 10 mg/kg vs. Placebo (14 Wochen). Baseline: median 85 Drop-Seizures/28 Tage. Mediane Reduktion der Drop-Seizure-Frequenz: 41,9% (20 mg/kg, p=0,005 vs. Placebo), 37,2% (10 mg/kg, p=0,002 vs. Placebo), 17,2% (Placebo). Häufigste Nebenwirkungen: Somnolenz, verminderter Appetit, Diarrhö (dosisabhängig); 6 Patienten (20 mg/kg-Gruppe) und 1 Patient (10 mg/kg-Gruppe) brachen wegen Nebenwirkungen ab.

10.1056/nejmoa1714631 View study →
S Devinsky et al. · 2017 · New England Journal of Medicine
1652 citations
Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome
Clear benefit RCT

n=120 Dravet-Syndrom (therapierefraktär), CBD 20mg/kg/d vs. Placebo über 14 Wochen; median konvulsive Anfallsreduktion 38,9% (CBD) vs. 13,3% (Placebo), adjustierte Differenz -22,8 Prozentpunkte (95%-CI -41,1 bis -5,4; p=0,01); 5% anfallsfrei (CBD) vs. 0% (Placebo).

10.1056/nejmoa1611618 View study →
S Thiele et al. · 2018 · The Lancet
881 citations
Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial
Clear benefit RCT

Phase-III-RCT (GWPCARE4) bei Lennox-Gastaut-Syndrom, n=171 (2–55 Jahre), randomisiert zu CBD 20 mg/kg/d vs. Placebo über 14 Wochen. Primärer Endpunkt: prozentuale Reduktion der monatlichen Drop-Seizure-Frequenz. Multizentrisch (24 Zentren USA, Niederlande, Polen). 14 Patienten in CBD-Gruppe, 1 in Placebo-Gruppe brachen ab. [Numerische Outcomes im Abstract abgeschnitten; Volltext zeigt signifikante Drop-Seizure-Reduktion vs. Placebo].

10.1016/s0140-6736(18)30136-3 View study →

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