A meta-analysis of 13 meta-analyses reports that cannabidiol (CBD) is effective for children and adolescents with seizures related to Lennox–Gastaut syndrome (LGS), Dravet syndrome (DS) and tuberous sclerosis complex (TSC) (Borowicz-Reutt et al. Molecules 2024;29:1981).
CBD is a phytocannabinoid with known anticonvulsant effects although its mechanism of action is not well-established. CBD has low affinity for cannabinoid receptors so its effects do not appear to be via agonism of the CB1 or CB2 receptors. Rather, the antiseizure properties of CBD may be through modulation of ion channels, inhibition of adenosine reuptake, modulation of GABAA and glycine receptors and/or reduced synthesis of inflammatory cytokines.
CBD was more effective when combined with clobazam in children, which appears to be due in part to a pharmacokinetic interaction. CBD inhibits clobazam metabolism by blocking cytochrome CYP 2C19 while clobazam inhibits CYP 2D6, which raises plasma levels of the CBD metabolite 7-hydroxy-CBD.
The efficacy of CBD has been examined in 10 meta-analyses and two systematic reviews. Most studies used doses of CBD 10-20 mg/kg/day (range 2.5-60 mg/kg/day). Adjunctive CBD reduced the intensity and frequency of seizures and the incidence of status epilepticus in a dose-dependent manner. Clinical improvements were also reported in cognition, behavior, mood, and quality of life domains independently of the seizure reduction.
One study noted better control of convulsive and non-convulsive seizures with adjunctive CBD in children with Lennox-Gastaut syndrome; however, CBD was not effective for non-convulsive seizures in younger patients with Dravet syndrome (Lattanzi et al. Drugs 2018;78:1791–1804).
The incidence of adverse effects was higher with adjunctive CBD, most notably for diarrhea, somnolence and sedation. Abnormal liver function tests were reported, most commonly in children treated with valproate and adjunctive CBD. Adverse effects resolved with a lower dose of the antiseizure medication or CBD dose reduction or withdrawal.
CBD was the only cannabinoid to demonstrate antiseizure efficacy. Other products (dronabinol, nabilone, nabiximols) were not effective in epilepsy and other seizure disorders (Bilbao et al. BMC Med 2022;20:259).
The authors cautioned against recreational marijuana use to treat seizures. Marijuana contains delta-9-tetrahydrocannabinol (THC). The efficacy of THC has not been demonstrated in seizure disorders and there are conflicting data on whether it has pro- or antiseizure effects.