“The efficacy of cannabidiol (CBD) with and without concomitant clobazam (CLB) was evaluated in stratified analyses of four large randomized controlled trials, two in Lennox-Gastaut syndrome and two in Dravet syndrome.
Results: The meta-analysis favored CBD vs. placebo regardless of CLB use. The treatment ratio (95% CI) of CBD over placebo for the average reduction in seizure frequency was 0.59 (0.52, 0.68; p<0.0001) with CLB and 0.85 (0.73, 0.98; p=0.0226) without CLB, and the 50% responder rate odds ratio (95% CI) was 2.51 (1.69, 3.71; p<0.0001) with CLB and 2.40 (1.38, 4.16; p=0.0020) without CLB. Adverse events (AEs) related to somnolence, rash, pneumonia, or aggression were more common in patients with concomitant CLB. There was a significant exposure/response relationship for CBD and its active metabolite.
Conclusions: These results indicate CBD is efficacious with and without CLB, but do not exclude the possibility of a synergistic effect associated with the combination of agents. The safety and tolerability profile of CBD without CLB shows a lower rate of certain AEs than with CLB.”