Cannabinoids and epilepsy treatment


Epilepsy is one of the most common neurologic disorders affecting 1 out of 23 persons. Nearly one-third of the epileptic patient population do not respond to anti-epileptic drug therapy and have persistent seizures. This gap in treatment options clearly indicates the need for additional treatments that can help fill the gap by reducing continued seizures with their unique mechanism of action.

Cannabinoids as a treatment option for epilepsy

Ancient Greek and Arabic medical texts were the first literature that mentioned the use of natural cannabinoids in the treatment of seizures. Cannabis-based products were first utilized as an anti-seizure medication in 1843. Medical literature of the 1850s and 60s also reported the effectiveness of cannabis in treating several medical conditions, including epilepsy. In contrast, a few small case studies of the 1980s and 90s reported contradictory results. The limitations of these studies were the variable concentration of CBD in the extracts. However, numerous other in vitro and in vivo studies documented the anti-epileptic effect.

The U.S. Food & Drug Administration (FDA) approved EPIDIOLEX® (cannabidiol, CBD) oral solution on June 25, 2018, to treat seizures associated with- Lennox-Gastaut syndrome and Dravet syndrome. This CBD product was a new medication option for pediatric epilepsy. It was approved for use in people two years of age or older. Epidiolex represents the first-ever FDA-approved medication that can treat seizures associated with Dravet syndrome.

The principle of the effect of cannabinoids on the human body

Humans have an endocannabinoid system (ECS) consisting of cannabinoid receptors, endocannabinoids, and enzymes. ECS is involved in several physiological processes and pathological conditions where it has a protective role. Cannabinoids interact with the cannabinoid receptors, i.e., CB1 and CB2, regulating these physiological and several pathological conditions such as epilepsy.

What cannabinoids are used to treat epilepsy?

Many early evidences, anecdotal reports, and small clinical trials suggested the efficacy of phytocannabinoids in epilepsy.

CBD: CBD is the most commonly analyzed anticonvulsant phytocannabinoid with sufficient data in many acute animal models but limited data in chronic models.  Literature has reported nearly more than 65 molecular targets of CBD. The exact mechanism of action of CBD as the anti-epileptic drug is still unknown, but literature documented the effect of CBD on the equilibrative nucleoside transporter(ENT), the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the α3 and α1 glycine receptors. Numerous studies also document the neuroprotective and anti-inflammatory effects of cannabinoids.

CBDV: Another phytocannabinoid, cannabidivarin (CBDV), a direct analog of CBD derived from cannabigerovarin (CBGV), has shown a favorable pharmacokinetic profile and anticonvulsant effects. At micro-and nanomolar concentrations, it inhibits the reuptake of AEA and 2-AG.

CBG: It is one of the important phytocannabinoids that is non-psychoactive. CBG potentially works as an antagonist of serotonin receptors. This data, along with other data, leads to the postulations that 5-HT2A receptor signaling is implicated in controlling neuronal excitability via GABAergic, glutamatergic, and monoaminergic neurotransmission. This acts as evidence of the possible anticonvulsant effects of CBG by direct modulation of activity at 5-HT2A receptors.

Types of epilepsy that cannabinoids help treat

A 2017 randomized, double-blinded, placebo-controlled study evaluated the efficacy of cannabinoids, i.e., CBD, in Dravet syndrome and reported a 50% reduction in convulsive seizure frequency. Three patients of this study were found to be seizure-free at the end of the trial, but the reduction in nonconvulsive seizures was not significant.

Similarly, a 2018 randomized, double-blind, placebo-controlled study used CBD as an intervention in patients with Lennox-Gastaut syndrome who had more than two drop seizures per week. This study documented the 50% reduction in drop seizure frequency. The intervention reduced the seizure frequency and recorded the data of patients who became drop seizures free during the maintenance phase. A similar study also reported the efficacy of CBD in treatment-resistant Lennox-Gastaut syndrome. CBD has proven efficacy as an adjunct therapy in drug-resistant childhood-onset epilepsy. The current evidence of the efficacy of cannabinoids such as CBD is limited to the rare and severe epileptic syndrome.

The benefits of cannabinoids in the treatment of epilepsy

Cannabinoids for epilepsy have been a hot debate in recent years. Numerous research studies have demonstrated the potential benefit of cannabinoids in treating specific epileptic patient populations resistant to traditional anti-epileptic drug (AED) therapies. Evidence from a reputed journal has shown cannabinoids as an effective treatment option for Dravet syndrome, Lennox-Gastaut syndrome, treatment-resistant Lennox-Gastaut syndrome, and drug-resistant childhood-onset epilepsy.

Cannabinoids can treat rare and severe epilepsy and prevent seizures in non-epileptic patients by maintaining the normal physiology of the body’s neurological system.

Side effects/disadvantages

The advantages associated with cannabinoids use include drowsiness, diarrhea, an upset stomach, changes in weight and appetite.

The benefits of using biosynthesized cannabinoids

Rare cannabinoids exist in minimal quantities in cannabis plants, making extraction and purification inefficient, costly, and environmentally taxing. It takes 10 kilograms of cannabis plants to produce less than 2 grams of rare cannabinoids. Cannabis cultivation is labor, time, and energy-intensive and can produce inconsistent yields prone to contamination from pests, mold, and pesticides. Significant regulatory oversight is also necessary during handling cannabis plants, which contain THC – a Schedule I compound in the United States.

Biomedican has developed a patented biosynthetic method of growing rare cannabinoids in proprietary yeast to address this issue. The unique process allows us to extract and purify the most demanded rare cannabinoids.

Biomedican’s patented method creates an engineered strain of yeast, Yarrowia Lypolitica (Y.L.), through sugar and water. This process can be easily upscaled to produce larger volumes of pure rare cannabinoids that can be used in countless products across a wide variety of industries. Our proprietary biosynthesis process and strain of proprietary yeast serve as a reliable source of pure low-cost clinical-grade cannabinoids biologically identical to those found in nature.

Our goal is to make rare cannabinoids widely available at a lower cost, so millions of people can benefit from their unique qualities.

Conclusion

Cannabinoids are being evaluated as a treatment option for various neurological conditions, including infantile spasm, Fragile X syndrome, Rett syndrome, and several neuropsychiatric diseases, including autism spectrum disorders and schizophrenia. Non-consistent bioavailability and pharmacokinetic parameters of plant-based cannabinoids can either halt these trials or interfere with results. The bioavailability of the cannabinoids under trials can be increased by using highly pure, organic, non-GMO, and 99% pharmaceutical-grade biosynthetic cannabinoids produced by Biomedican.

Since the FDA has approved cannabinoids, i.e., CBD, to treat Dravet syndrome and Lennox-Gastaut syndrome, the researchers are now evaluating other rare cannabinoids to treat infantile spasms, Fragile X syndrome, and Rett syndrome. Biosynthetic cannabinoids produced by Biomedican are the most reliable source of pure low-cost clinical-grade cannabinoids for these clinical studies.

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Content author Dr.Saba IqbalAuthor posts

Saba Iqbal

Dr. Saba Iqbal is a contributing writer for BioMedican. She's a clinical pharmacist turned writer. Dr. Saba's education includes a doctoral degree in pharmacy (Pharm D) from the University of Sargodha, Pakistan. In search of a career that would take advantage of her medical and pharmaceutical skills, Dr. Saba found medical writing – a career path a few medical students consider. In her journey "from a medical bench to pen," she has worked with several startups for many years managing content on biotech products, pharmaceuticals, drugs, devices, and techniques. While keeping up with the latest trends in medical writing, she aims to use her writing skills to clearly communicate complex scientific, medical, and health information to the potential investor and general audience.