Cannabidiol (CBD) has a novel CB1/CB2-independent anti-seizure mechanism and is approved for epilepsy in Lennox–Gastaut syndrome, tuberous sclerosis and Dravet syndrome. ^{Reference Whitney, Jauhari and Jain1} Kang et al. ^{Reference Kang, Boelman, Connolly, Huh and Datta2} showed a 22% (95% CI, 11.9% to 33.7%) responder rate in a retrospective pediatric cohort (n = 61) of heterogeneous Developmental/Epileptic Encephalopathies (DEEs). This outcome was commensurate with a prior meta-analysis. ^{Reference Saranti, Dragoumi, Pavlogiannis, Pavlou and Zafeiriou3} They also found similar seizure outcomes in patients with DEEs with approved and off-label indications, and similar observations were noted in a multi-center study from Europe. Emerging evidence thus supports potential expansion of CBD indications in pediatric epilepsy.

Nearly half of patients had <50% seizure reduction, but many continued CBD for non-seizure benefits, including improved sleep, behavior and mood. Such benefits have been noted previously, often more common in those with better seizure control. ^{Reference Chemaly, Kuchenbuch and Losito4}

Authors also reported further improved seizure control in two-thirds of patients transitioned from artisanal CBD to purified CBD (n = 9). Limited evidence indicates that purified CBD may achieve higher serum CBD concentration and consequent better seizure control, as compared to the artisanal CBD. ^{Reference Cohen, Bahar, Conry and Schreiber5} Artisanal CBD contains variable amounts of tetrahydrocannabidiol (THC), which is shown to have both anti- and pro-convulsant effects in animal models. However, its clinical use is limited by its CB1-mediated psychoactive effects. With improved access to purified CBD for patients with approved indications, it can be foreseen that more patients may switch from artisanal to purified CBD.

CBD’s efficacy must be contextualized against alternatives for DEEs. A recent meta-analysis showed a pooled responder rate of 56.8% and high treatment retention rates in patients with highly refractory DEEs treated with Cenobamate. ^{Reference Samanta and Naik6} Safety and efficacy data from phase 1b/2a trial for Bexicaserin are also encouraging. Invasive neuromodulation strategies like deep brain stimulation and vagal nerve stimulation may also be effective in DEEs, especially if offered early. Further, precision therapies for DEEs are rapidly evolving and hold promise for the future.

In this study, adverse events were reported in 30% of patients and four patients (22%) discontinued CBD due to intolerability. However, the rate of adverse events was lower than reported in the published literature, which may be attributable to the implementation of a slower dose titration schedule.

The management of DEEs is challenging; selection of drugs aimed at distinct pathways may enhance success rates in a polytherapy. Given a novel mechanism of action, adjuvant effectiveness and other non-seizure benefits, CBD is an additional tool in a physicians’ armamentarium.