Cannabinoids

Cannabidiol (CBD) was first isolated from the plant cannabis sativa by Roger Adams in 1940.¹ Cannabis sativa’s psychoactive (affects the mind) compound tetrahydrocannabinol (THC) was then isolated, with subsequent research focused on the antipsychotic activities of cannabinoids. The results concluded that the antipsychotic activity was due to THC, not CBD. However, due to the conformational (shape or structural) changes, CBD has many therapeutic roles. According to studies, CBD has a potential role in epileptic patients who don’t primarily show a response to conventional anti-epileptic drugs.²

Epilepsy

Epilepsy is a neurological condition affecting 70 million people worldwide, with a high incidence in the elderly and infants. In 1997, the World Health Organisation (WHO), in collaboration with the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy, launched the Global Campaign Against Epilepsy, and their results in 2015 World Health Assembly addresses the specific and effective treatment of epileptic patients. The management of epilepsy includes anti-epileptic medications such as sodium and potassium channel blockers; however, most patients show resistance to conventional medications; therefore, these patients can benefit from CBD therapy.³

CBD mechanism of action in epilepsy

CBD has a positive effect on the different types of seizures in animal models. CBD acts on intracellular calcium channels through G protein-coupled receptors and adenosine-mediated signalling. By inhibiting the intracellular calcium, CBD decreases the excitatory current and seizure frequency. Furthermore, CBD antagonises the excitatory messages, leading to inhibition of adenosine reuptake.⁴

CBD pharmacokinetic properties

CBD combines or dissolves with fats and does not enter systemic circulation well when taken orally. Additionally, the dose of CBD in the body takes a long time to halve and is rapidly distributed to all parts of the body, including the brain, because CBD combines or dissolves with fats. Furthermore, CBD is a potent inhibitor of proteins involved in metabolism, such as CYP2C9, CYP2D6, and CYP2C19.⁵

Clinical studies on CBD therapy in epilepsy

• A CNN special documentary "Weed" introduced a girl named Charlotte Figi, having Dravet syndrome with medically intractable seizures (cannot be controlled by medication) and intellectual impairment. Charlotte did not respond to several antiepileptic drugs. At the age of five years, her mother began administering high-CBD cannabis extracts to her (later known as Charlotte's Web), developed by the Stanley brothers in Colorado. In response to CBD oil, Charlotte had improvements in controlling seizures and cognition
• A study surveyed members of a Facebook group of parents using CBD extracts to treat their children's seizures. Of 19 participants, 13 had Dravet syndrome, four had Doose syndrome, one had Lenox Gastaut Syndrome (LSG), and one had idiopathic epilepsy; of 16 patients who had experienced a decrease in the frequency of seizures, two (11%) became totally seizure-free
• Another research study reported the responses from 117 parents of children with epilepsy, including 53 who had infantile spasms or LGS, to evaluate the perceived efficacy of CBD. All the parents reported a reduction in seizure frequency and 14% reported their children were completely seizure-free
• Another retrospective study examined the medical records of 75 children and adolescents with epilepsy who were given oral cannabis extracts. Their parents reported a 57% improvement in seizure frequency and a 50% reduction in seizures was present in 33% of the children

As with the first two studies, an improvement in behaviour, alertness, speech, and motor capabilities occurred in a subgroup of the patients. A better response rate was seen in the LGS and Dravet syndrome patients; however, patients with Doose syndrome did not show a response to the treatment. The background electroencephalographic (ECoG) abnormalities remained unchanged, although seizure control was better among those patients.⁵

Long-term impact of CBD on epilepsy

Reduction in seizure severity and frequency

The most important benefit of CBD is the lowering of the severity and frequency of seizures. Clinical studies, especially those related to severe forms of epilepsy, such as Dravet syndrome and Lennox-Gastaut syndrome, demonstrated a great reduction in the seizure number of persons. In some people, CBD treatment resulted in completely seizure-free periods.

Quality of life improvement

People consuming CBD have an improved quality of lifewhich can be attributed to factors such as decreased seizures, improved moods, and reduced anxiety. Most of the patients’ emotional and psychological states improve, thus allowing them to engage in more activities and further enhance their quality of life.⁷

Fewer side effects in comparison with other drugs

Traditional antiepileptic drugs (AEDs) have many side effects, from fatigue and dizziness to mood swings. In comparison, CBD is much better tolerated with fewer reported side effects. In most cases, CBD is an alternative, safer and/or complementary treatment that ensures conventional medication can be taken at a lower dose, thus reducing the side effects.

Neuroprotection

Studies have discovered that CBD has neuroprotective properties, which protect brain cells from damage during seizures; this is especially important for chronic seizure disorders because they will continue to improve cognitive performance and brain health.

Anti-inflammatory effects

CBD has anti-inflammatory properties that could explain CBD’s anti-epileptogenic activity. Decreased neuroinflammation could contribute to the stabilisation of neuronal activity, resulting in fewer seizures that are easier to control; this mechanism provides further advantage to patients for whom seizure control may be compromised.

Availability and range of forms

CBD has a range of forms, including oils, capsules, edibles, and topical (applied to skin) applications, which can make it easier for patients to build this into their daily habits.

Increasing popularity and research

There will be an increase in acceptance amongst the treatment providers, or health practitioners, as more studies are carried out and verification of CBD benefits continues to emerge; this encourages better communication between patients and doctors and could encourage mixed treatment approaches when appropriate.⁸

FAQs

Is CBD effective in all forms of epilepsy?

Answer: There are variations in the response of epileptic patients to CBD. Although there has been an impressive benefit for some forms of epilepsy, such as the most severe forms, Dravet and Lennox-Gastaut syndromes, patients vary greatly in their potential responses to CBD therapy for other forms of epilepsy.

Does liver function need monitoring in CBD therapy?

Answer: Monitoring of the liver function is imperative in a patient receiving CBD therapy, especially higher doses, or when combined with another therapy.Possible liver enzyme alteration: CBD alters the activity of a few cytochrome P450 enzymes in the liver, which are responsible for metabolizing several drugs. Alteration of these expressions leads to changes in the metabolism of others, thus maybe resulting in interactions.
Increased risk of elevated liver enzymes: certain studies showed that elevated liver enzyme levels were noted in patients who received high doses of CBD. Monitoring is usually done regularly to ascertain any liver problems.

Summary

Huge amounts of evidence indicate CBD has a long-term effect on epilepsy and there is broad promise in treatment for patients who are looking for reliable alternatives to traditional treatment options; most noticeably, this could be the case for those who have treatment-resistant epilepsy. CBD often diminishes seizure frequency considerably, enhances the quality of life, and encompasses an improved safety profile when compared with most traditional medications for treating epilepsy. In addition to most patients experiencing fewer seizures, they improved emotional well-being and satisfaction with their lives.
In addition to neuroprotective properties, anti-inflammatory effects further support CBD as an effective agent in the treatment of epilepsy. Further studies and continuous research would be needed to understand its mechanism of action, optimum dosing, and long-term effects. However, hopes remain high that CBD could become part of the treatment protocols for epilepsy.
With increased research and societal acceptance, CBD is expected to alter the therapeutic landscape of those afflicted with epilepsy. The possibility of CBD therapy in conjunction with conventional AED treatments allows healthcare professionals to better tailor therapy, thus improving the lives of many patients.