Overview

Epilepsy is a neurological condition that causes recurrent seizures. During these episodes, the brain suffers an electrical disturbance, often presenting intense involuntary muscular reactions, but also stiffness, behavioural changes, odd sensations and even loss of consciousness. The cause behind epilepsy can be unclear, but, in general, it is triggered by brain damage from strokes, tumors, infections, physical trauma or genetic factors. One can manifest this condition at any point in life, most commonly as a child, or as an elderly.¹

Epilepsy can be classified into different categories.. The focal is characterised by an electrical discharge that happens in a specific part of the brain, while generalised epilepsy happens after a widespread discharge, affecting both brain hemispheres. The focal and generalised types originate different seizures, as they manifest depending on the areas of the brain that experience the disturbance. Additionally, some syndromes can be directly related to recurrent epileptic episodes.²

Epilepsy is a chronic condition without a cure. Treatment is essential to improve the patient’s quality of life by reducing the intensity and frequency of seizures, but finding the best option for each case can be a challenge. For some individuals, it may take multiple trials of different therapies before symptoms are adequately controlled.²

Many studies on antiepileptic treatments have investigated the effectiveness of cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant. It is isolated from parts of the plant that are low in tetrahydrocannabinol (THC), a compound that causes mind-altering effects. In territories that legalise its use and commercialisation, CBD is widely incorporated in foods, oils, supplements and cosmetics. Many products are not regularised, requiring caution and awareness of the consumer and are not recommended for all, but seizure treatment based on CBD is well established, safe and presents positive outcomes for epilepsy patients.³

CBD seizure treatment has gained attention and supporters, especially by people who were barely or non-responsive to traditional treatment. Many of the epilepsy syndromes fall into this category, causing individuals with epilepsy to suffer cruel episodes from childhood, many times losing hope of having their condition under control. Studies show that CBD is significantly beneficial for this population, even coming to stop seizure episodes. Many other health conditions are constantly being investigated for their response to CBD treatment, with great efficacy or promising results so far (anxiety, addiction, chronic pain, for example), indicating the importance of cannabidiol and its versatility.⁴

Mechanism of action of CBD in epilepsy

Neuronal excitation and seizures

Signals are transmitted between neurons through a tiny gap called the synapse. Within this space, a process called synaptic transmission occurs, where neurotransmitters—chemical messengers—are released by one neuron to carry the signal to the next. An electrical impulse, once it travels along the length of a neuron and reaches its end, depends on this chemical communication to either continue the signal to another neuron or halt it. When the signal needs to be transmitted, excitatory neurotransmitters stimulate the next neuron, causing it to generate its own electrical impulse, thereby continuing the chain of communication. In contrast, inhibitory neurotransmitters suppress the signal, preventing further transmission. The inability to balance between excitatory and inhibitory signals between synapses leads to symptoms of seizures.⁵

Endocannabinoid system

The human body contains a complex network known as the endocannabinoid system (ECS), which plays a crucial role in maintaining physiological balance. It is composed of cannabinoid receptors and chemicals that stimulate them, the endocannabinoid:⁶

• CB1 receptor: widely present throughoutthe brain. Due to their prevalence, it highly influences regulation of most neurotransmitters, sgnificantly modulates systems related to hunger, body temperature, and alertness
• CB2 receptor: mainly found in the immune system, and modulates a variety of inflammatory responses. Because they are not involved in producing psychoactive effects, they are considered a promising therapeutic target
• Endocannabinoids: similar to the chemicals found in the cannabis plant, but naturally produced by the body

Interaction between CBD and cannabinoid receptors

At the synapse, chemicals are responsible for signals to pass from one neuron to another. Specific elements were found to, in one end of the synaptic gap, promote excitation, while, on the other end, to weaken inhibition. In summary, they have a dangerous tendency to create a feedback loop that amplifies neuronal excitation.⁵

CBD can interact with receptors and disrupt this process. Due to its structural similarity to endocannabinoids, CBD can interact with cannabinoid receptors and other molecular targets within the synapse. By modulating these interactions, CBD interferes with the excitatory signaling that drives this feedback loop. As a result, it helps to reduce neuronal excitability, which is crucial in managing and preventing seizures.⁵^,⁷ This stabilising effect on neural activity is one of the reasons why CBD has become a promising therapeutic agent in the treatment of epilepsy.

Types of epilepsy and recommended CBD dosing

CBD dosing for epilepsy treatment is dependent on various aspects and should be decided with professional guidance and supervision. Recommended values ​​are estimates obtained from clinical trials and approved by local regulatory entities.

Generalised epilepsy

Seizures caused by an abnormal electrical discharge spread on both brain hemispheres, usually resulting in loss of consciousness. Generalised epilepsy can be caused by different types of seizures⁸ including:

• Absence seizures: appear as a daydream, the person stares at one point for a few seconds, being consciously absent
• Atonic seizures: presents a decrease in muscle tone, the body collapses by the loss of strength
• Myoclonic seizures: the person feels a sudden and local energy discharge, like a jolt
• Tonic seizures: the body is fully stiff and the person experiences loss of consciousness
• Clonic seizures: body spasms, muscles intensely contract and relax
• Tonic-clonic seizures: known as the convulsive seizures, both tonic and clonic happen at the same time

Focal epilepsy

The abnormal electrical discharge happens in a specific part of the brain.⁹

• Simple focal seizures (aura): can affect motor functions, involuntary movements, sensory perceptions or psychic reactions (illusions, for example)
• Complex focal seizures: a complication of a focal seizure, the person can experience blank starring and automatic actions, without purpose

Lennox-Gastaut Syndrome (LGS)

Lennox-Gastaut Syndrome (LGS) is a rare epilepsy syndrome. These patients can experience all types of seizures, especially the tonic and atonic types. This severe and debilitating form of epileptic episodes start manifesting in childhood. There is currently no cure and treatment relies on continuously cycling between different medications, as most cases are resistant to conventional anti-seizure drugs.¹⁰

Dravet syndrome (DS)

A rare genetic disease that first manifests in early childhood. It causes affected individuals to experience recurrent seizures and compromised neurological development. Throughout disease progression, seizures often become more severe. Managing DS is complex, as the daily intake of some anticonvulsant medication is not recommended.¹¹

CBD dosing and treatment

Overall, for epilepsy treatment, CBD oil is usually taken twice a day in a maintenance dose of 5mg/kg. The maximum recommended dosage is 10mg/kg twice a day. It should never be abruptly introduced or stopped, the administration should be followed by health professionals to avoid increase in seizure activity.¹²

In 2018, the Food and Drug Administration (FDA) approved a CBD-based medication (Epidiolex) for patients who live with Lennox-Gastaut or DSs.¹³

Factors influencing CBD dosing

• Patient age and weight: importance of weight-based dosing (mg/kg), special considerations for pediatric patients
• Severity and frequency of seizures: adjusting doses for seizure control, starting low and titrating up gradually
• Drug interactions: potential interactions with antiepileptic drugs (AEDs), importance of monitoring liver enzymes during treatment

Safety and side effects of CBD in epilepsy treatment

• Common Side Effects: drowsiness, fatigue, decreased appetite
• Serious but Rare Effects: liver enzyme elevation, drug interactions
• Long-term Use Considerations: safety profile based on clinical trials

Clinical evidence supporting CBD use in epilepsy

• Major Clinical Trials: many clinical trials have been investigating the efficacy of CBD in the epilepsy treatment with positive results. Evidence points to CBD supporting a decrease in seizure frequency
• FDA Approval of Epidiolex: a hallmark in the prescription of CBD. Promotes popular awareness and increases support for studies around CBD being used as treatment for epilepsy. It is based on real-world applications and ongoing research

Summary

Cannabidiol is a treasured compound found in the cannabis plant. It does not trigger psychoactive effects and has a significant role in well-being. Isolated CBD has been studied for its medical properties and its benefits for many conditions like anxiety and chronic pain, but one of its most established and promising uses is for the treatment of epilepsy. An individual who suffers from epilepsy recurrently experiences uncomfortable, painful and vulnerable episodes, which triggered by excessive electrical discharge within the brain, causing functional impairments like uncontrollable muscle contraction, completely relaxed, unconscious and even a complete collapse.

Symptoms depend on the type of seizure and the region of the brain affected by the electrical excitation. Many genetic syndromes are related to frequent and intense seizures, and these conditions often manifest in early years of life, meaning that young children having to deal with aggressive episodes. Epilepsy syndromes often present a challenge in its management, with constant changes in treatment and anticonvulsant drug resistance.

Long-term studies with CBD and its effect in different types of epilepsy, including rare syndromes, show positive results. Due to its structural similarity to natural compounds in the body, CBD can reduce neuronal excitability, helping to prevent the abnormal discharges that cause seizures. In 2018, the FDA approved a CBD-based drug for certain epilepsy syndromes, confirming its safety and efficacy. This event shows that the medical uses of cannabidiol are not only possible, but can be preferred for some cases in which traditional approaches do not bring benefits enough or at all.