Table 1.
Completed cannabidiol clinical trials in epilepsy (https://clinicaltrials.gov/). The table shows the efficacy and safety of CBD in different forms of epilepsy. In all studies, CBD is used as adjunctive therapy to conventional antiepileptic drugs.
| Identifier | Study Title | Subjects | Conditions | CBD Dose | Concomitant AEDs | Efficacy | Security | Ref |
|---|---|---|---|---|---|---|---|---|
| NCT02987114 | A Study to Evaluate the Safety, Tolerability and Efficacy of Oral Administration of PTL101 (Cannabidiol) as an Adjunctive Treatment for Pediatric Intractable Epilepsy | 16 children (2 to 15 years) | Pediatric Intractable Epilepsy | 25–450 mg/kg/day | - | - | - | - |
| NCT02324673 | Cannabidiol Oral Solution in Pediatric Participants With Treatment-resistant Seizure Disorders | 61 children (1 to 17 years) | Resistant Seizure Disorders | 10, 20, 40 mg/kg/day | - | Improvement of illness | SAEs in 5% of patients with medium-dose and in 9.5% with high-dose | - |
| NCT02551731 | Cannabidiol Oral Solution for Treatment of Refractory Infantile Spasms | 9 infants (6 to 36 Months) | Refractory Infantile Spasms | 20–40 mg/kg/day | - | Complete resolution of spasm in 14.3% of children after 14 days of treatment | No SAEs were recorded | - |
| NCT02318602 | Cannabidiol Oral Solution as an Adjunctive Treatment for Treatment-resistant Seizure Disorder | 52 children and young adults (1 to 18 years) | Treatment-resistant Seizure Disorder | 10, 20, 40 mg/kg/day | - | - | SAEs in 77.78% of infants, in 38.46% of children and in 0% of adults | - |
| NCT02224703 | GWPCARE2 A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome | 150 children and young adults (2 to 18 years) | Dravet Syndrome | 10, 20 mg/kg/day | - | - | - | - |
| NCT02695537 | Safety, and Tolerability of Epidiolex In Patients (Ages 1–19 Years) With Intractable Epilepsy | 100 children and young adults (1 to 18 years) | Intractable Epilepsy | 5–50 mg/kg/day | CLB, Valproate, Levetiracetam, Phenobarbital, Clonazepam, Phenytoin, Carbamazepine, Lamotrigine, Oxcarbazepine, Ethosuximide, Topiramate, Vigabatrin, Zonisamide, Eslicarbazepine, Ezogabine, Pregabalin, Perampanel, Rufinamide, Lacosamide |
- | 4 children with concomitant valproate showed elevate damage of liver function | [78] |
| Reduction of seizures of 63.6% after 12 weeks of treatment | Improvement of AE Profile | [79] | ||||||
| NCT02700412 | University of Alabama at Birmingham (UAB) Adult CBD Program | 100 children and adults (15 to 99 years) | EpilepsySeizures | 5–50 mg/kg/day | - | 4 children with concomitant valproate showed elevate damage of liver function | [78] | |
| Reduction of seizures of 63.6% after 12 weeks of treatment | Improvement of AE Profile | [79] | ||||||
| NCT02224560 | Efficacy and Safety of GWP42003-P for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults (GWPCARE3) | 225 children and adults (2 to 55 years) | Epilepsy Lennox Gastaut Syndrome | 10, 20 mg/kg/day | CLB Valproate Lamotringine Levetiracetam Rufinamide |
The median percent reduction in seizures frequency from baseline was 37.2% in the 10 mg/kg/day CBD group; 41.9% in the 20 mg/kg/day CBD group | SAEs were reported in 19.40% of patients at the dose of 10 mg/kg/day of the CBD and in 15.85% at the 20 mg/kg/day | [75] |
| NCT02091206 | A Dose-ranging Pharmacokinetics and Safety Study of GWP42003-P in Children With Dravet Syndrome (GWPCARE1) | 34 children (4 to 10 years) | Dravet Syndrome | 5, 10, 20 mg/kg/day | CLB Valproate Stiripentol Levetiracetam Topiramate |
- | TEAEs in 5 patients; SAE in 10% of patients at the dose of 5 mg/kg/day, in 25% at the 10 mg/kg/day and in 11.11% at the 20 mg/kg/day dose. 6 patients with concomitant valproate had elevated ALT or AST |
[73] |
| NCT02091375 | Antiepileptic Efficacy Study of GWP42003-P in Children and Young Adults With Dravet Syndrome (GWPCARE1) | 120 children, young adults (2 to 18 years) | Dravet Syndrome | 20 mg/kg/day | CLB Valproate Stiripentol Levetiracetam Topiramate |
The median frequency of seizures decreased from 12.4 to 5.9, compared to the placebo-treated group | SAEs in 16.39% of patients | [74] |
| NCT02224690 | A Study to Investigate the Efficacy and Safety of Cannabidiol (GWP42003-P; CBD) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults (GWPCARE4) | 171 children and adults (2 to 55 years) | Lennox-Gastaut Syndrome | 20 mg/kg/day | CLB Valproate Lamotrigine Levetiracetam Rufinamide |
The monthly frequency of seizures decreased by a median of 43,·9% from baseline in the CBD group | Serious TEAEs occurred in 4 patients;SAEs in 23.26% of patients. 16 of the 36 patients on valproate had transaminase elevations | [76] |
| NCT02224573 | GWPCARE5 - An Open Label Extension Study of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet or Lennox-Gastaut Syndromes | 264 children, and adults (2 years and older) | Dravet Syndrome Lennox-Gastaut Syndrome | - | CLB Valproate Stiripentol Levetiracetam Topiramate |
The monthly frequency of seizures decreased by a median ranged from 38% to 44% | SAEs in 29.2% of patients | [77] |
| NCT02565108 | A Randomized Controlled Trial to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol | 20 adults (18 to 65 years) | Epilepsy | 20 mg/kg/day | CLB | All participants reduced the maintenance dose of CBD from 10% for the day | 2 patients withdrew from the study due to SAEs (seizure cluster) | - |
| NCT02564952 | An Open-label Extension Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol | 18 adults (18 to 65 years) | Epilepsy | Initial 20 mg/kg/d titrated to maximum dose of 30 mg/kg/day | CLB | - | SAEs in 11% of patients | - |
CBD: Cannabidiol; TEAEs: Treatment-emergent adverse events; SAEs: serious adverse events; AST: aspartate transferase; ALT: alanine transferase.