Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study

Abstract

The objective of this study was to characterize the changes in adverse events, seizure severity, and frequency in response to a pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex®) in a large, prospective, single-center, open-label study. We initiated CBD in 72 children and 60 adults with treatment-resistant epilepsy (TRE) at 5 mg/kg/day and titrated it up to a maximum dosage of 50 mg/kg/day. At each visit, we monitored treatment adverse events with the adverse events profile (AEP), seizure severity using the Chalfont Seizure Severity Scale (CSSS), and seizure frequency (SF) using seizure calendars. We analyzed data for the enrollment and visits at 12, 24, and 48 weeks. We recorded AEP, CSSS, and SF at each follow-up visit for the weeks preceding the visit (seizures were averaged over 2-week periods). Of the 139 study participants in this ongoing study, at the time of analysis, 132 had 12-week, 88 had 24-week, and 61 had 48-week data. Study retention was 77% at one year. There were no significant differences between participants who contributed all 4 data points and those who contributed 2 or 3 data points in baseline demographic and AEP/SF/CSSS measures. For all participants, AEP decreased between CBD initiation and the 12-week visit (40.8 vs. 33.2; p < 0.0001) with stable AEP scores thereafter (all p ≥ 0.14). Chalfont Seizure Severity Scale scores were 80.7 at baseline, decreasing to 39.2 at 12 weeks (p < 0.0001) and stable CSSS thereafter (all p ≥ 0.19). Bi-weekly SF decreased from a mean of 144.4 at entry to 52.2 at 12 weeks (p = 0.01) and remained stable thereafter (all p ≥ 0.65). Analyses of the pediatric and adult subgroups revealed similar patterns. Most patients were treated with dosages of CBD between 20 and 30 mg/kg/day. For the first time, this prospective, open-label safety study of CBD in TRE provides evidence for significant improvements in AEP, CSSS, and SF at 12 weeks that are sustained over the 48-week duration of treatment.

Efficacy and Tolerance of Synthetic Cannabidiol for Treatment of Drug Resistant Epilepsy

“…As this is an ongoing study, numbers of patients receiving treatment for more than 12 months are too small to assess the long-term efficacy. Nevertheless, retention rates at 6 and 12 months are 78.1 and 73.1%, respectively, and comparable with other open label studies using plant-derived CBD (18). The role of clobazam-cannabidiol interaction in seizure reduction has been discussed before and is not fully understood (1).…”

Cannabinoids for drug‐resistant seizures in a critically ill patient—Case report and literature review

“…CBD has been studied in recently conducted RCTs; however, the results are difficult to extrapolate to adults with epilepsy as these studies were conducted mainly in paediatric populations. In addition, these trials do not include hospitalized patients.…”

“…On reviewing the published literature in detail, we found 3 previously published case reports over the last two decades, detailing 4 patient cases of adults using cannabis to reduce uncontrolled seizures . We also found 1 case series study, 7 RCTs, 1 observational study and 5 surveys examining the efficacy and safety of cannabis use in epilepsy. (Table S1) These studies showed a reduction or complete freedom from seizures following the use of CBD compared with placebo.…”

Crossing the Line: Care of a Pediatric Patient with Intractable Seizures and Severe Neuropathic Pain in Absence of Access to Medical Marijuana

“…11 Many other offlabel investigations into medical effectiveness of CBD have demonstrated effectiveness. [12][13][14] CBD, unlike its common cannabis-based cousin THC, does not elicit adverse physiological effects in up to 50 times recommended daily doses 15 and has even been shown to counteract intoxicating effects of THC. 16 Despite physiological effects being demonstrated through CBD usage, molecular mechanisms and the pharmacokinetic profile of CBD are much less understood than THC.…”