---
title: "Cannabidiol for Dravet and Lennox-Gastaut Syndrome"
slug: cbd_seizure
version: 1.1
timestamp: 2026-04-20T00:00:00Z
date: 2026-04-20
specialty: Neurology (Epilepsy)
canonical_url: https://mahmood726-cyber.github.io/rapidmeta-finerenone/protocols/cbd_seizure_protocol_v1.1_2026-04-20.md
app_url: https://mahmood726-cyber.github.io/rapidmeta-finerenone/CBD_SEIZURE_REVIEW.html
license: MIT
---

# Cannabidiol (Epidiolex) in Dravet + LGS (GWPCARE 1/2/3/4)
## A Living Systematic Review and Meta-Analysis Protocol

**Protocol version:** 1.1
**Frozen:** 2026-04-20T00:00:00Z
**Specialty:** Neurology (Epilepsy)

---

## 1. Review Title and Registration

**Title:** Pharmaceutical-Grade Cannabidiol (Epidiolex) for Drug-Resistant Dravet Syndrome and Lennox-Gastaut Syndrome: A Living Systematic Review and Meta-Analysis of the GWPCARE1-4 Phase 3 RCTs

**Registration:** Protocol frozen 2026-04-20T00:00:00Z. Pre-registration mechanism: **GitHub-canonical-URL freeze**. **Authors:** Mahmood Ahmad (corresponding). drmahmoodclinic@pm.me.

---

## 2. PICO

| Element | Specification |
|---|---|
| **Population** | Children/young adults with drug-resistant Dravet syndrome (GWPCARE1/2) or Lennox-Gastaut syndrome (GWPCARE3/4) |
| **Intervention** | Cannabidiol (Epidiolex) 20 mg/kg/d oral solution adjunctive to existing antiepileptic regimen |
| **Comparator** | Matched placebo |
| **Outcome (primary)** | Proportion with >=50% reduction in convulsive (Dravet) or drop (LGS) seizure frequency at week 14; RR |

---

## 3. Eligibility / Search / Selection

Inclusion: phase III pivotal, Dravet or LGS, CBD 20 mg/kg/d vs placebo adjunctive, >=50% responder endpoint available. Exclusion: open-label extensions, phase II dose-finding, CBD in other epilepsy syndromes (tuberous sclerosis complex — separate app candidate). Two-reviewer adjudication; PRISMA 2020.

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## 6-7. Data Extraction + RoB

Per-arm >=50% responder counts + RR, median % seizure reduction (continuous sensitivity), somnolence/decreased-appetite/LFT elevation rates (especially with concomitant valproate). RoB 2 LOW across D1-D5 all 4 trials. Author sign-off per provisional-RoB banner.

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## 8. Synthesis

- DerSimonian-Laird RE IVW on log-RR; HKSJ t-df=k-1 with floor; PI computable at k=4.
- Subgroup: Dravet vs LGS; concomitant valproate (LFT signal).
- Sensitivity: median % seizure reduction (continuous).
- Bayesian half-normal(0, 0.5) prior on tau (log-RR).

---

## 9-10. GRADE / Reporting

Standard GRADE. Class-level CBD pool across Dravet (convulsive seizure primary) and LGS (drop-seizure primary) — pre-specified indirectness downgrade for seizure-type heterogeneity. Effect direction invariant. PRISMA 2020.

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## 11. Living-MA Update Cadence

3-monthly. Triggers: CBD in TSC (GWPCARE6), CBD long-term extension (OLE cohorts), next-generation cannabinoid formulations.

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## 12-14
Aggregate-data only. No CoI, no funding.

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## Appendix A. AMSTAR-2

| # | Domain | Rating | Evidence |
|---|---|---|---|
| 1 | PICO | Yes | §2 |
| 2 | Registered protocol | Yes (partial) | GitHub-canonical-URL freeze |
| 4 | Search strategy | Yes | §4 |
| 7 | Excluded-studies list | Yes | Screening tab |
| 9 | RoB | Yes | Author-confirmed provisional |
| 11 | Statistical methods | Yes | §8 |
| 13 | RoB interpretation | Partial | Indication indirectness noted |
| 15 | Publication bias | Yes | k=4, formal tests + funnel |

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## Changelog
- **v1.1** (2026-04-20) — Initial editor-review-revision release.