Sclérose en plaque et CBD, que sait-on ?

Multiple sclerosis and CBD, what do we know?


1. Description of Multiple Sclerosis (71)

Multiple sclerosis is a chronic, progressive autoimmune disease of the CNS. It is a pathology of the young subject.

It is characterized by inflammation of myelin, the sheath that surrounds and protects nerve fibers in the central nervous system, the optic nerves and the spinal cord. Nerve impulses are altered, we then find in these patients neuro-sensory disorders (visual blur, decreased acuity) and motor disorders (paresthesias and painful muscle aches), but also balance disorders. , concentration, urinary and sexual disorders.

We define 2 phases:

- The flare-up: appearance, reappearance or worsening of neurological signs occurring subacutely during at least
least 24 hours, with more or less complete recovery. To treat flare-ups, corticosteroids are generally used, which have many long-term side effects: insomnia, mood fluctuations, water retention, osteoporosis, etc.

- Progression: continuous worsening, over a period of at least 6 months, of neurological symptoms.

2. Action of CBD

Few studies have been carried out on the specific use of CBD in multiple sclerosis. But, the anti-inflammatory, immunosuppressive and neuroprotective properties of CBD can slow neurodegenerative progression.

2.1 Anti-inflammatory action of CBD

CBD is a powerful anti-inflammatory that acts on several levels:

- it activates vanilloid receptors ( TRPV1 ) responsible for the regulation of several inflammatory agents such as TNF alpha, IFN gamma, IL6, IL4 or even IL12 , which destroy myelin-producing cells. (100)

- It slows down the activation of immune cells such as T and B lymphocytes and therefore prevents the production of antibodies , which destroy the myelin sheath. (215)

- It inhibits the enzymatic activity of COX1 and COX2 , responsible for the production of prostaglandins from arachidonic acid. However, prostaglandin is a mediator of inflammation. (101)

Neuroinflammation destroys myelin, and is responsible for disease progression.

Researchers have studied the effect of CBD as a topical treatment, in the form of a cream, on multiple sclerosis. Daily application of this 1% CBD cream allowed recovery from hind limb paralysis in mice, and also reduced lymphocytic infiltration and demyelination, typical of this pathology. In addition, daily application led to a reduction in the release of CD4 and CD8 T cells and the expression of the main pro-inflammatory cytokines (IL10, IFN γ , TGF β , iNOS, etc.). (216)

2.2 Action of CBD on glutamate – neuropathic pain and excitotoxicity

Glutamate is an excitatory neurotransmitter of the central nervous system. Multiple triggers (such as oxidative stress, calcium overload) can lead to abnormalities in glutamate signaling. Disruption of this homeostasis can affect all physiological functions and interactions between brain cells, leading to excitotoxicity. (217)

Excitotoxicity is a process of neuronal destruction that occurs when glutamate, present in excess, excessively stimulates receptors, and leads to damage or death of nerve cells. According to this 2014 study, it is now widely accepted that alterations in glial cells surrounding neurons have a role in the progression of the pathology (142). Modulation of glutamate release and transport, as well as receptor blockade could be relevant targets for MS treatment.

However, CBD inhibits the release of glutamate and reduces oxidative stress. Indeed, it activates the presynaptic CB1 receptors coupled to the Go and Gi proteins, which leads to an inhibition of adenylate cyclase, then a reduction in cAMP and the activity of protein kinase A. Hyperpolarization of the terminals presynaptics leads to a closure of calcium channels, and therefore a reduction in the release of stored neurotransmitters such as glutamate. (218)

In addition, this study demonstrated that CBD causes a reduction in glutamate toxicity through its powerful antioxidant activity. Even if the mechanism of action is not yet known, this neuroprotective activity is undeniable. (44)

In this pathology where the nerves are damaged, most patients suffer from neuropathic pain. In patients suffering from neuropathic pain, elevated glutamate levels are found. Indeed, glutamate releases a neuropeptide (substance P) responsible for the perception of pain. (142)

A study carried out on mice in 2017 showed promising results on the anti-apoptotic properties of CBD against the neurodegenerative processes of MS. (219)

2.3 Action of CBD on spasticity

Spasticity is a symptom that affects almost 70% of patients, characterized by involuntary, very intense and long-lasting contractions of striated muscle fibers, causing pain. According to certain studies, this symptom is also associated with excess glutamatergic transmission. Activation of CB1 receptors by anandamide could therefore be beneficial for the treatment of this symptom. However, we know that CBD inhibits the breakdown of anandamide, and therefore increases the concentration of available anandamide. (8-220)

2.4. Action of CBD on depression

Depression is a symptom that affects more than one in two patients. It is an essential symptom to treat because it can delay the improvement of symptoms by reducing adherence to treatment and reducing physical activity.

The action of CBD in depression is detailed in this article, CBD and depression.

2.5. CBD and PI3k/Akt/mTOR pathway (221)

A recent study analyzed the effect of CBD on mouse models of an experimental type of multiple sclerosis. The researchers demonstrated a reduction in the activity of the PI3k/Akt/mTOR pathway, involved in the regulation of the cell cycle and metabolism. Treatment with CBD made it possible to restore this signaling pathway, and would therefore be, according to the researchers, “a new potential therapeutic target for the treatment of MS. »


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