It is the third most common neurological disorder effecting more people then cerebral palsy, multiple sclerosis and Parkinson’s disease combined. Epilepsy is a seizure disorder comprised of over 40 syndromes that can lead to physical and mental defects. Epilepsy has an economic burden estimated at $17.6 billion annually. The disease is unrelenting with and estimated 40% of epileptic patients pharmacoresistant to current medications (seizures persist in spite of medical intervention). Annually an estimated 25-50,000 people die of seizures or related causes. The need exists for improved therapies for patients.
Cannabis and Epilepsy
Matt Figi, Father of Epileptic child and inspiration for Charlotte’s Web a low THC cannabis strain
“These families are really desperate. They’ve tried all the drugs, and nothing has worked. This (medical cannabis) is the only option left.”
Dr. Margaret Gedde, a Stanford-educated Colorado Springs pathologist
Dr. Alan Shackelford (physician for epileptic child)
Cannabis has been reported to have anti-convulsant properties for thousands of years. However, only recently have studies performed in animal models and humans proven this observation. Cannabis contains over 85 cannabinoids; the most common one being THC. THC is widely credited with giving cannabis its psychedelic effects. However, recent studies in animal and humans have shown that other cannabinoids, not THC, are effective in managing seizures. Animals studies have shown extracts rich in cannabidivarin (CBDV) and/or cannabidiol (CBD) are effective at eliminating seizures in mice ((Hill et al. Br J Pharmaco). Recently in a human clinical double-blind study, it was reported 84% of children saw a reduction of seizure activity when medicated with a CBD-enriched cannabis ((Porter et al. Epilepsy Behav.). Most cannabis available in the recreational cannabis market has been selected to be high in THC and low in other cannabinoids which will provide patients with the unwanted side effect of feeling euphoric and most likely will be ineffective in managing seizure symptoms.
The mechanism of action for cannabis and/or cannabinoids to prevent seizures is not completely understood. Studies have shown cannabinoids decrease key genes (Fos, Casp 3, Ccl3, Ccl4, Npy, Arc, Penk, Camk2a, Bdnf and Egr1) associated with epilepsy in animal models(Amada et al. PeerJ. 2013). It has been hypothesized that down regulation of these genes could provide the answer for why these substances provide epileptic relief. However, additional mechanisms of action have been proposed. For example, cannabinoids are also known to modulate neurotransmission, modulate the endocannabinoid system, reduce neuro-inflamation, control ion-cannels, and affect oxidative stress; all which could lead to a decrease in seizures (Izzo et al. Trends Pharmacol Sci. and Vezzani A. Curr. ).
Recently, GW Pharmacueticals received Orphan Drug Designation for its drug Epidolex which is a CBD extract for the treatment of Dravet’s, a specific epileptic syndrome. Their data illustrates the ability of CBD to treat seizures in acute models of epilepsy with significantly fewer motor side effects than existing anti-epileptic drugs (Jones et al. J Pharmacol Exp Ther. ). However, Epidolex is not currently approved in the US for the majority of epileptic syndromes and does not contain CBDV or other potential cannabinoids that may work synergistically to prevent seizures in patients.
Currently, many epileptic patients are self-medicating with cannabis or cannabis extracts to prevent seizures. However, this carries risk including patients receiving cannabis which may not contain any of the cannabinoids scientifically shown to prevent seizures. Most recreational cannabis is high in THC (the primary psychedelic cannabinoid) and low in CBD and other non-psychedelic cannabinoids which are the cannabinoids shown to decrease seizure activity. As standardization of cannabis products have not been accomplished, it is difficult to conduct broad clinical research. Many researchers, physicians and patients lack access to clinical cannabis strains. Research on the anti-epileptic effects of medical cannabis is just begining; in the last decade results have been promising; but by understanding the genome and environmental factors that affect cannabinoids we can begin to expand understanding of potential therapeutic compounds. Verda Bio is creating CBT (cannabinoid based therapeutics) to provide consistent cannabinoid therapies to epileptic patients.
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