To evaluate the efficacy of cannabidiol (CBD) in achieving seizure freedom (SF) and ≥50% responder rates (RR50) in patients with Dravet syndrome (DS), Lennox–Gastaut syndrome (LGS), and Tuberous Sclerosis Complex (TS).

CBD has emerged as an adjunctive therapy for refractory epileptic syndromes. While individual trials report benefit, pooled evidence across syndromes and doses remains essential for clinical decision-making.

Randomized controlled trials (RCTs) comparing CBD to placebo in DS, LGS, and TS were identified (PMIDs: 28813226, 29768152, 29540584, 29395273, 32119035, 33346789). Outcomes included SF and RR50. Event counts and sample sizes were extracted. Odds ratios (OR) were pooled using a random-effects model (DerSimonian-Laird).

A total of six RCTs comprising 604 participants in the experimental group and 599 in the control group were included. The pooled fixed-effect OR for SF was 7.93 (95% CI: 4.17–15.09), with no observed heterogeneity (I² = 0%) and a prediction interval of 3.66–16.73. Subgroup analyses revealed the greatest effect in DS at 20 mg (OR 13.35; 95% CI: 5.33–33.40) and LGS at 20 mg (OR 5.92; 95% CI: 1.03–34.17). Fail-safe N calculations (Rosenthal = 98; Orwin = 11) supported the robustness of these findings. For the outcome of 50RR, the pooled OR was 2.50 (95% CI: 2.00–3.33) with a prediction interval of 1.90–3.44, again with no heterogeneity (I² = 0%). The most pronounced benefits were observed in LGS at 20 mg (OR 3.05; 95% CI: 1.84–5.04) and DS at 20 mg (OR 2.46; 95% CI: 1.46–4.14).

CBD significantly improves SF and 50RR in DS, LGS, and TS, with the strongest effects at 20 mg. Benefits are consistent and robust, though absolute SF remains modest. Higher doses enhance efficacy but require safety considerations, supporting CBD as an effective adjunct for refractory epileptic syndromes.