Tuberous sclerosis complex (TSC) is an autosomal‐dominant genetic disorder with highly variable expression. The most common neurologic manifestation of TSC is epilepsy, which affects approximately 85% of patients, 63% of whom develop treatment‐resistant epilepsy. Herein, we evaluate the efficacy, safety, and tolerability of cannabidiol (CBD), a nonpsychoactive compound derived from the marijuana plant, as an adjunct to current antiepileptic drugs in patients with refractory seizures in the setting of TSC.

Eighteen of the 56 patients who have enrolled in our current expanded‐access study of cannabidiol for patients with treatment‐resistant epilepsy carry a diagnosis of TSC. After an initial baseline period of 1 month, patients began treatment with CBD. The initial dose of 5 mg/kg/day was increased by 5 mg/kg/day every week up to a maximum dose of 50 mg/kg/day, if tolerated. Weekly seizure frequencies, percent change in seizure frequencies, and responder rates were calculated during the 2nd, 3rd, 6th, 9th, and 12th month of treatment with CBD.

The median weekly seizure frequency during the baseline period was 22.0 (interquartile range [IQR] 14.8–57.4), which decreased to 13.3 (IQR 5.1–22.1) after 3 months of treatment with cannabidiol. The median percent change in total weekly seizure frequency was −48.8% (IQR −69.1% to −11.1%) after 3 months of treatment. The 50% responder rates over the course of the study were 50%, 50%, 38.9%, 50%, and 50% after 2, 3, 6, 9, and 12 months of treatment with CBD, respectively. In patients taking clobazam concurrently with CBD (n = 12), the responder rate after 3 months of treatment was 58.3%, compared to 33.3% in patients not taking clobazam (n = 6). Twelve (66.7%) of 18 patients in this study experienced at least one adverse event thought possibly related to CBD; the most common adverse events were drowsiness (n = 8, 44.4%), ataxia (n = 5, 27.8%), and diarrhea (n = 4, 22.2%).

Although double‐blind, placebo‐controlled trials are still necessary, these findings suggest that cannabidiol may be an effective and well‐tolerated treatment option for patients with refractory seizures in TSC.