Table 1

Study-level summaries of included randomised controlled trials

StudyDesignSampleTreatmentPharma.  gradeOutcomes measuredResultsAdverse events and serious adverse eventsBias assessment† /GRADE assessment
Ames and Crindland30 Randomised clinical trial12 adults with frequent seizures not controlled by anticonvulsant therapy
(drug-resistant epilepsy)
100 mg CBD or placebo sunflower oil 3 times a day for 1 week, then 2 times a day for 3 weeksNot statedSeizure reduction- The trial was abandoned before the second stage of the trial could take place. No significant differences in seizure frequency were observed between groups.Reported:
drowsiness
Unclear risk/low
Cunha et al 25 Randomised, double-blind, placebo-controlled trial15 adults (mean age=24; range 14–49; 26.7% male) with secondary generalised epilepsy
(drug-resistant epilepsy)
100 mg CBD or placebo glucose capsule, taken orally 2–3 times per day, for 8–18 weeksNot statedReported seizure improvement; self-reported subjective improvement- Four of seven (~57%) patients receiving CBD showed complete seizure freedom, compared with 1/8 (12.5%) placebo patients.
- All 7 CBD patients showed some sort of improvement in seizure frequency, compared with only 2/8 (25%) placebo patients.
- One CBD patient withdrew from the study, whereas two patient receiving placebo withdrew.
Somnolence (57.1%)
Painful gastric sensation (14.3%)
High risk/moderate
Devinsky et al 26 Randomised, double-blind, placebo-controlled trial120 children and adolescents (mean age=9.8; range=2–18; 52% male) with Dravet syndrome
(drug-resistant epilepsy)
20 mg/kg/day CBD or placebo, taken orally for 14 weeks, as an adjunctive treatmentYesChange in seizure frequency, caregiver global impression of change- Three CBD patients achieved total seizure freedom during the test period, no placebo patients achieved seizure freedom (P=0.08).
- Twenty-six CBD patients (~43%) had a >50% reduction in seizures, compared with 16 patients (~27%) in the placebo group.
- Thirty-seven caregivers (~62%) judged their child’s overall condition to be improved in the cannabidiol group, as compared with 20 (~34%) in the placebo group (P=0.02).
- Nine CBD patients withdrew from the study, 8 of which were due to adverse events. In comparison, three placebo patients withdrew, with only one being due to adverse events.
Somnolence (36%)
Diarrhoea (31%)
Decreased appetite (28%)
Fatigue (20%)
Vomiting (15%)
Fever (15%)
Lethargy (13%)
Upper respiratory tract infection (11%)
Convulsion (11%)
Serious:
Elevated liver aminotransferase enzymes (20%)
Status epilepticus (4.9%)
Low risk/high
GW Pharmaceuticals 27 Randomised, double-blind, placebo-controlled trial225 patients (mean age=16; range=2–55) with
Lennox-Gastaut syndrome
(drug-resistant epilepsy)
i) 10 mg/kg/day CBD for 14 weeksYesChange in seizure frequency, change in QoL and caregiver global impression of change- Patients randomised to 10 mg/kg/day of CBD achieved a median reduction in monthly drop seizures of 37%, in comparison with 17% in those patients in the placebo group (P=0.0016).
- One patient receiving 10 mg/kg/day CBD withdrew due to adverse events, as did one placebo patient.
All cause (83.6%)
Serious:
All cause (17.8%)
Unclear risk/high
ii) 20 mg/kg/day CBD for 14 weeksYesChange in seizure frequency, change in QoL and caregiver global impression of change- Patients taking 20 mg/kg/day of CBD showed a median reduction in monthly drop seizures of 42%, compared with 17% in the placebo group (P=0.0047).
- Six patients receiving the higher dose (20 mg/kg/day) withdrew due to adverse events, compared with one placebo patient.
All cause (93.4%)
Serious:
All cause (17.1%)
Thiele et al 28 Randomised, double-blind, placebo-controlled study171 patients (mean age=15.4; range=2–45; 51.5% male) with Lennox-Gastaut syndrome
(drug-resistant epilepsy)
20 mg/kg/day CBD or placebo, taken daily for 14 weeks, as an adjunctive treatmentYesChange in seizure frequency, caregiver impression of overall improvement- Five of 86 CBD patients achieved complete seizure freedom during the maintenance period, compared with none in the placebo group.
- Thirty-eight patients (~44%) taking CBD had >50% decrease in seizures, compared with 20 (~24%) patients taking placebo.
- Forty-two (~58%) CBD patients were reported (by either themselves or a caregiver) to have achieved an improvement in their overall condition, compared with 29 (~34%) placebo patients.
- Fourteen CBD patients withdrew from the study, compared with just one patient given placebo.
Diarrhoea (18.6%)
Somnolence (15.1%)
Fever (12.8%)
Decreased appetite (12.8%)
Vomiting (10.5%)
Serious:
All cause (23.3%)
Unclear risk/high
Trembly and Sherman 29 Double-blind, cross-over, placebo-controlled add-on trial12 adults with incompletely controlled seizures
(drug-resistant epilepsy)
100 mg CBD or placebo 3 times per day for 26 weeksNot statedMonthly seizure episodes- Changes to seizure frequency were not statistically analysed, but authors report some reduction in seizure frequency for patients taking CBD.None reportedUnclear risk/moderate
  • †Bias assessment based on risk of bias for randomised studies.

  • Studies are presented in alphabetical order; adverse events are reported for participants receiving cannabinoids and experienced by >10% of sample.

  • CBD, cannabidiol; GRADE, Grades of Recommendation, Assessment, Development and Evaluation;  Pharma. grade, pharmaceutical grade cannabinoid product; QoL, quality of life.