Hemp is a variety of Cannabis Sativa L. plant historically grown for fibrous materials found in its stalks and seeds. It has been used to make items such as clothing fiber, upholstery, and other household items.
A summary of the Epidiolex clinical trials is found below:
Does cannabis help seizures?
Providers do not need a special license or certificate to prescribe Epidiolex. Epidiolex is the first and only plant-based treatment derived from cannabis for use as a treatment for seizures with FDA approval. Other formulations of medical cannabis have not been approved by the FDA.
On June 25, 2018, the U.S. Food & Drug Administration (FDA) approved EPIDIOLEX ® (cannabidiol, CBD) oral solution for the treatment of seizures associated with two epilepsy syndromes – Lennox-Gastaut syndrome and Dravet syndrome – in people two years of age or older. Epidiolex represents a new medication option for children with these types of epilepsy. It is also the first ever FDA approved medication to treat seizures in Dravet syndrome.
Hemp traditionally contains lower concentrations of THC and higher levels of CBD. Cannabinoids extracted from hemp plants, including CBD, have until recently been classified as marijuana and considered Schedule I substances. Per the DEA, Schedule I substances currently have no accepted medical use and have a high potential for abuse. A federal law* enacted in December 2018, however, reclassifies hemp and hemp-derived CBD as an agricultural commodity and exempts it from the list of Schedule I Drugs.
The concentrations of CBD, THC, and CBC appeared to increase linearly with dosage in six of the seven participants, suggesting dose-independent pharmacokinetics for these participants within this dosage escalation trial. The greater than proportional increase in CSS, Min CBD with the final dosage increase in participant A-04 may suggest dose-dependent pharmacokinetics with saturation of first-pass metabolism and an increase in the oral bioavailability. Participant A-04 did not exhibit any change in clinical status or in anticonvulsant therapy to explain this disproportional increase in CSS, Min. To confirm the possible non-linear pharmacokinetics in children, a dosage escalation study involving a larger sample size and a higher dose beyond the doses used in the current trial will be necessary. The possibility of dose-dependent PK, though, raises a safety concern, which also warrants further investigation in pediatric patients and suggests a need to limit dose sizes and not to simply continue increasing doses until an appropriate effect is observed.
Following a month of CBD at 5–6 mg/kg/day, the four participants with a >50% reduction in average daily seizure frequency, had CSS, Min CBD levels ranging from 14.8 to 24.4 ng/mL. After a month of CBD at 10–12 mg/kg/day, the five participants with a >50% reduction in average daily seizure frequency, had CSS, Min CBD level ranging from 42.5 to 124.7 ng/mL. The CSS, Min CBD levels corresponding with the CBD dosage at which the three participants became seizure free, ranged from 54.8 to 78.9 ng/mL ( Figure 3A ).
Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 Δ 9 -tetrahydrocannabinol (THC): CBD up to 10–12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms, and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css, Min) of selected cannabinoids were quantified.
Effect of CHE on Steady State Levels of Anticonvulsants
CARE-E is a multi-center, phase 1, open-label, dosage escalation study using a Health Canada approved and Good Manufacturing Practices certified 1:20 THC:CBD CHE as adjunct therapy to treat children with epileptic encephalopathy. The primary objectives were to assess the safety and efficacy of CBD-enriched CHE, whereas secondary objectives included an analysis of trough steady state (CSS, Min) levels of CBD, THC, and cannabichromene (CBC); as well as an assessment of the correlation between cannabinoid levels and therapeutic effect. CBC levels were measured as the CHE used in this study contained 4% CBC by volume. We present results for seven CARE-E participants recruited at the University of Saskatchewan site.
Results: All seven participants tolerated the CHE up to 10–12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. CSS, Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. CSS, Min CBD levels associated with a >50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, CSS, Min levels of THC remained lower than what would be expected to cause intoxication.
Prior to enrollment, written and informed consent was obtained from the child’s parents or legal guardian. This study received a No Objection Letter (NOL) from Health Canada, was approved by the University of Saskatchewan Biomedical Research Ethics Board and registered with ClinicalTrials.gov ( <"type":"clinical-trial","attrs":<"text":"NCT03024827","term_id":"NCT03024827">> NCT03024827).
The three participants who became seizure free were taking long acting benzodiazepines (clobazam or clonazepam) but clobazam and clonazepam levels did not increase for two of these participants. This suggests that, while CBD and long acting benzodiazepines likely have a synergistic effect, this is not necessarily due to an increase in plasma benzodiazepine levels.