Epidiolex and the Treatment of Epilepsy

Cannabidiol and conventional treatment of epilepsy

The anticonvulsive properties of cannabidiol have been studied by different independent researches. In 2010, the Journal of Pharmacology and Experimental Therapeutics published the report of a study examining the anti-epileptiform and anti-seizure potentials of cannabidiol using in-vitro electrophysiology and in-vivo in animal models. In line with previous research, results from this research affirmed that CBD inhibits epileptiform activity in vitro and seizure in vivo. There is other accumulated scientific evidence supporting the use of cannabidiol in the treatment of rare forms of epilepsy. 

Epidiolex and rare forms of epilepsy

On June 25, 2018, the FDA approved Epidiolex as an oral cannabidiol drug for the treatment of epilepsy associated with Lennox-Gastaut syndrome and Dravet syndrome in patients who are at least two years old. Lennox-Gastaut syndrome is a severe form of childhood epilepsy characterized by multiple types of seizures, including tonic seizure and atonic seizures. 

Children with this rare condition often present with delayed development, neurological deficiency, cognitive impairment, and behavioral problems, including agitation, aggressiveness, autism, and hyperactivity. Although the causes of Lennox-Gastaut syndrome are known in most diagnosed cases, there is no standard therapy regimen for this condition. In fact, many conventional anti-seizure medicines are ineffective in the treatment of Lennox-Gastaut syndrome, and medications such as clobazam, lamotrigine, and valproic acid only offer partial relief. 

Dravet syndrome is another rare form of childhood epilepsy characterized by seizure episodes involving one side of the body. This syndrome develops during the first year of life in otherwise healthy infants and is resistant to conventional anti-seizure medications. Children with Dravet syndrome often present with photosensitive seizures, a crouched gait, low motor tone, and stunted growth. Just as in Lennox-Gastaut syndrome, the causes of Dravet syndrome are well known. 

Epidiolex drug presentation and pharmacology

The active component in Epidiolex is a purified form of cannabidiol available as an oral medication formulated to contain 100mg of active drug per millimeter of solution. Each bottle of Epidiolex contains 100ml of drug solution presented as a clear colorless to a yellow solution with a strawberry flavor. The drug pack also comes with two 5ml syringes for dispensing doses of the medication in small quantities as needed in children. It is recommended that blood tests for serum transaminase and bilirubin levels should be conducted for all patients to be treated with Epidiolex. In many cases, the starting dose of Epidiolex in the treatment of rare forms of epilepsy is 2.5mg per kg taken twice daily. Depending on the drug, a patient’s response, the caregiver might decide to increase the starting dose as treatment progresses. 

The mechanism of action of Epidolex is still largely unknown. However, many research reports have suggested that cannabidiol—the active ingredient in Epidiolex—exerts its anti-seizure effects by modulating the endocannabinoid system specifically by inhibiting anandamide degradation and decreasing the neuronal excitability of the brain cells. By influencing the process of cell-to-cell communication in the brain, cannabidiol can reduce the rate at which certain parts of the brain initiate and receive neuronal signals. Alternatively, cannabidiol has been demonstrated to act simultaneously on different molecular targets playing important roles in neuronal excitability and intracellular calcium levels. Judging from available research data, Epidiolex effectively treats the different forms of epilepsy by acting on the brain in multiple ways. 

Epidiolex and the improvement in managing epilepsy

As expected, the medical community placed tremendous hope on Epidiolex for the treatment of epilepsy. Given the different anecdotal evidence supporting cannabidiol use in epileptics and the results of clinical trials conducted on Epidiolex, it was not entirely surprising that the new drug revolutionizes the modern treatment of epilepsy. In March 2020, JAMA Neurology published the result of the second positive Phase 3 trial for Epidiolex in children with Dravet syndrome. Results published suggested that Epidiolex at a dose of 10 and 20mg/kg/day significantly reduced the frequency of seizure in children compared with placebo. 

About 49% of the participants taking the 20mg/kg/day dose experienced a 50% or greater reduction in the frequency of convulsive seizures during the treatment period. In 2018, Lancet also published the result of a double-blind, placebo-controlled phase 3 trial investigating the potential of cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome. At the end of the trial, the researchers concluded that cannabidiol is well tolerated and effective for the treatment of drop seizures in Lennox-Gastaut syndrome. The success of the new drug in the treatment of epilepsy is evident in the impressive sales revenues recorded by GW Pharmaceuticals. There are also other clinical trials and research inquiries underway to examine the potential of Epidiolex and other CBD-based medications in the treatment of rare and chronic diseases in humans. 

REFERENCES

• https://www.epilepsy.com/learn/types-epilepsy-syndromes/dravet-syndrome
• https://www.epilepsy.com/learn/types-epilepsy-syndromes/lennox-gastaut-syndrome-lgs
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514832/#!po=1.35870
• https://pubmed.ncbi.nlm.nih.gov/19906779/
• https://ir.gwpharm.com/news-releases-details/jama-neurology-publishes-results-positive-phase-3-trials