Cannabis Extract in Refractory Epilepsy Study

The purpose of this study is to examine whether a low dose of CBD+THC will decrease the frequency of convulsive seizures in adults with drug-resistant epilepsy, when used in addition to standard anti-epileptic drugs (AEDs). This study will also study the genes associated with epilepsy and whether different epileptic syndromes respond to treatment with CBD+THC.

Background: Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the two major compounds found in the cannabis plant. Reports from patients, families, and the scientific community suggest that CBD (when used as an add-on therapy) decreases the number of convulsive seizures in children and adults with Dravet syndrome, Lennox-Gastaut syndrome, and Tuberous sclerosis complex.

Trial design: Phase III, double-blind, randomized, placebo-controlled, parallel-group trial, followed by an open phase where treatment allocation will be revealed and all participants will either continue or begin receiving the active study drug.

Participants: Adults (18 years of age and older) with drug-resistant epilepsy, including patients with Dravet and Lennox Gastaut syndromes, and patients with frequent convulsive seizures (e.g., tonic, tonic-clonic, atonic, drop attacks, and focal motor seizures).

Interventions: Capsules containing a ratio of 16 CBD: 1 THC oil at a maximum total daily dose of approximately 300 mg of CBD per day, divided into equal doses in the morning and evening.

Comparator: Placebo capsules containing high-oleic sunflower oil and no active or medicinal ingredients.

Outcomes: Frequency of seizures; side effects; blood levels of AEDs, CBD, THC, and liver enzymes; impact on cognition and quality of life; genetics.

Sample size: A total of 80 participants (40 assigned to treatment and 40 to control group) recruited from Toronto Western Hospital in Toronto, and University Hospital in London, Ontario.

Time: Each participant will be enrolled for approximately 16 to 18 weeks, while the clinical trial is expected to take place over a period of two years.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of epilepsy according to the ILAE classification.
* At least 4 motor seizures per month at the start of the study, despite treatment with at least two different anti-epileptic drugs (given concurrently or sequentially) for at least one year.
* At least 4 motor seizures per month during the prospective baseline phase (4 weeks) with no 21-day seizure free periods.
* Stable dose(s) of the same AED(s) for one month prior to screening.
* Agrees not to take any cannabinoids during the study or any other investigational compound for one month before the study or outside cannabinoids during the study.
* Is planning to stay in Canada for the duration of the trial.
* Is able to travel to one of the study sites for in-person visits with the study physicians and to a local lab for blood collection.
* Has access to telephone, computer, and internet for regular correspondence and to complete the study questionnaires.

Exclusion Criteria:

* Participation in a study involving administration of an investigational compound within one month of Visit 1.
* Evidence of clinically significant non-epileptic disease (cardiac, respiratory, gastrointestinal, hepatic, hematologic, or renal disease, etc.) that in the opinion of the investigators could affect the patient's safety or trial conduct.
* Progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
* Occurrence of psychogenic seizures in the previous year.
* History of drug misuse/abuse (other than cannabinoids). Consideration may be given to allowing inclusion of subjects with remote history of drug abuse (within a defined relevant time period).
* Multiple drug allergies (dermatological, hematological, or organ toxicity) or more than one severe drug reaction(s).
* Pregnancy, breastfeeding.
* Known or suspected hypersensitivity to cannabinoids, or any of the excipients of the investigational medicinal product.
* Patients with a history of major depression, suicidal ideation or attempted suicide, schizophrenia or any other psychotic disorder, patients with a family history of schizophrenia.