Peut-on soigner l'épilepsie grâce au CBD ? Maison Sativa

Can epilepsy be treated with CBD? House Sativa

1. Description of the epileptic pathology

Recognized since Antiquity, this very common neurological disease still holds many mysteries. Today, it is estimated that there are around fifty epileptic diseases (or epileptic syndromes). We are therefore no longer talking about epilepsy but about epilepsies, a set of diseases whose manifestations and origins are very varied.

They are characterized by synchronized and abnormal excitation of a group of neurons in the cerebral cortex, which can subsequently spread to other areas of the brain. This causes a sudden, intense and prolonged electrical discharge causing the symptoms of the attack: involuntary movements, auditory or visual hallucinations, absences, etc.

The causes of epileptic disease are multiple: a stroke, a tumor, hypoglycemia, a genetic component, head trauma, chronic alcoholism or meningitis for example. It sometimes happens that no cause is found, in which case we speak of idiopathic epilepsy.

We distinguish generalized seizures from partial seizures.

- Generalized seizures follow a synchronized excitation of neurons from both cerebral hemispheres. Generally, the patient loses consciousness, and presents tonic motor signs (muscle contractions), and/or myoclonic (muscle twitches).

- The manifestations of focal seizures are very varied because they depend on the brain area involved. We may experience stiffness , tingling , visual or auditory hallucinations, language disorders , etc.

According to several theories, the appearance of epileptic seizures is partly linked to abnormalities in the activation of ion channels or neurotransmitters. Indeed, we find a decrease in the level of GABA and an increase in that of glutamate at the synaptic level. Activation of NMDA receptors could also be linked to the repetition of seizures. But other cellular pathways and other neurotransmitters seem involved in the complex genesis of this pathology.

No treatment can cure epilepsy, but following drug treatment generally stabilizes the disease. The treatments, however, are often highly toxic.

2. Effectiveness of CBD in the management of epilepsy

There is evidence of the use of cannabis to treat epilepsies in some ancient civilizations such as China and Persia. This is certainly one of the oldest uses of CBD.

Recently, CBD has been considered by the scientific community as a serious avenue for treating or at least reducing the intensity and frequency of epileptic seizures refractory to other treatments. Indeed, a large-scale study published at the end of 2018 has removed the last doubts about the effectiveness of CBD in the treatment of epilepsy. Researchers observed a 37 to 41% reduction in seizures with CBD in patients with Dravet and Lennox-Gastaut syndrome. (233–235)

The story of Charlotte Figi is certainly the best known. Young girl suffering from Dravet syndrome refractory to conventional treatments, saved by CBD.

A 2013 study conducted in Colorado on 11 patients with epilepsy showed a decrease in seizure frequency in all patients, with almost complete resolution in 77% of them. (236)

Another 2015 study of 117 pediatric patients showed that 85% of parents reported a decrease in seizure frequency, and 14% even noted that their child no longer had seizures at all. (237)

Israeli researchers have also been interested in the potential of CBD in the treatment of refractory pediatric epilepsy. The study included 74 patients: 89% of them reported a reduction in seizure frequency, 7% reported worsening seizures, which led to discontinuation of CBD treatment. Additionally, researchers observed improvements in behavior and alertness, language, communication, motor skills and sleep. Reported adverse reactions included drowsiness, fatigue, gastrointestinal upset, and irritability . (238)

A review published in 2017 includes research from 10 American epilepsy centers on the effectiveness of cannabidiol in epilepsy. The doses of CBD tested ranged from 2 to 5 mg/kg/day . Several studies have shown the effectiveness of CBD in the treatment of these epileptic disorders, with very few adverse effects, most of which were mild, such as drowsiness or diarrhea . However, the researchers specify that further studies are necessary to clarify the precise mechanism of action of CBD in this pathology. (239)

A Mexican study came to the same conclusions: of 53 children with refractory epilepsy, 81% reported a reduction in seizures; a moderate to significant reduction in 51% of cases, and a cessation of seizures in 16% of cases. The number of medications used was reduced in 20% of cases and no serious adverse effects were reported . (240)

In patients with febrile infection-related epilepsy syndrome (FIRES), refractory to conventional antiepileptic treatments, CBD reduced the frequency and duration of seizures in 6 out of 7 patients. On average, 4 antiepileptic drugs been stopped. (241)

3. Mechanism of action of CBD

The mechanisms by which CBD exerts its antiepileptic effects are not fully understood, but several targets appear to be involved. Modulation of intracellular calcium via TRPV1 , GPR55 or ENT channels by CBD allows the reduction of neuronal excitability and neuronal transmission. Indeed, CBD antagonizes GPR55 at excitatory synapses, desensitizes TRPV1 channels and inhibits ENT1 adenosine reuptake transporters, which leads to an increase in extracellular adenosine, and a decrease in intracellular calcium . (242,243)

3.1. Modulates TRPV1 receptor activity

TRPV1 expression is increased in human epilepsy and plays a role in cortical excitability ( 244 ). CBD is an agonist of TRPV1 receptors, and quickly causes their desensitization, and thus reduced the amplitude and duration of the epileptic seizure. (145). Hyperphosphorylation of TRPV1 receptors would therefore be involved in the appearance of epileptic seizures. CBD controls this overactivity and thus reduces the frequency of seizures.

3.2. Modulates GPR55 receptor activity (245)

Researchers have studied the action of CBD on the pro-excitatory effects of a GPR55 agonist involved in epilepsy. They demonstrated that the effects of the agonist ligand were completely blocked by pretreatment with CBD, giving it antiepileptic properties.

3.3. Increases extracellular adenosine levels (243,246)

Adenosine is described as an endogenous modulator of neuronal excitability. It is an endogenous anticonvulsant. It binds to adenosine A1 receptors which mediate the inhibition of presynaptic calcium influx and synaptic hyperpolarization. CBD blocks ENT1 receptors and thus allows an increase in adenosine, which leads to a reduction in epileptic seizures. Furthermore, CBD blocks transient melastatin channel receptor type 8 (TRPM8), enhances 5-HT1A and TRPA1 receptor activity. (247)

3.4. Anticonvulsant

CBD has demonstrated anticonvulsant effects in animal models of generalized seizures and in limited human trials. There is a significant reduction in the incidence of serious attacks and mortality, as well as a reduction in muscle contractions during attacks. (248)

3.5. Neuroprotective

The neuroprotective activity of CBD seems linked to its anti-inflammatory and antioxidant effects. It reduces the toxicity of glutamate and hydrogen peroxide, and is more powerful than ascorbic acid or tocopherols, renowned antioxidants. (44,249)


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