Central nervous system disorders are uniquely improved by cannabinoids, and many individuals have found success using CBD for multiple sclerosis. Researchers think that endocannabinoid signaling dysfunction may be partially responsible for the typical degradation of myelin in cases of multiple sclerosis.
What is multiple sclerosis (MS)
Multiple sclerosis is an autoimmune disease which results in the destruction of the myelin sheath, a layer of insulation which protects neurons and preserves the strength of their signals. MS affects roughly 3 million people worldwide, with about 200 new cases each week in the United States. As MS causes the progressive loss of myelin, nerve signals facilitating vision, movement, feeling, and cognition can become disrupted.
Spasticity is the most common characteristic of multiple sclerosis. Spasticity is temporary contraction or loss of muscle tone due to erratic neuronal signaling. It can result in jerky movements or the feeling that your muscles are heavy or sticky.
Multiple sclerosis symptoms manifest as both acute, short-term “flare-ups” – temporary periods of severe symptoms – and progressive, long-term loss of motor control, feeling, cognition, and/or vision. The differences between these two distinct phases of multiple sclerosis shed light on the underlying pathology that leads to this debilitating condition.
Cause(s) of multiple sclerosis
Multiple sclerosis is characterized by an autoimmune reaction that degrades the myelin which insulates and protects nerves in the brain and spinal cord. The exact cause of the disease is not completely understood, but it involves three distinct mechanisms of pathology:
- Inflammation of brain tissue, specifically of white matter (WM), is the first step of disease progression. WM is comprised of myelinated neurons that send signals over long distances.The myelin sheath is a fatty, white insulator that allows signals to pass efficiently over long stretches of a neuron, especially in the spinal cord and peripheral nervous system. Non-myelinated neurons make up grey matter: the “noodle” part of our brain that handles most processing. White matter conveys signals from grey matter to the spinal cord or to other areas of the brain.Inflammation is a destructive process that significantly disrupts normal cellular function. When it occurs at the wrong time or place, inflammation leads to structural changes, loss of function, and cell death. In the brain, immune system dysfunction has obvious and severe implications.
- Demyelination of neurons in various brain areas impedes the ability of a neuron to pass a signal over long distances, just as a cable that gets stripped of its insulation eventually fails to conduct a signal.After a period of inflammation and, therefore, demyelination, oligodendrocytes (the repair cells of the central nervous system) begin to remyelinate affected areas. This produces scar tissue known as lesions or scleroses, hence multiple “sclerosis”. MS lesions are visible on MRI scans and are often several millimeters in width, encompassing large areas of white matter, not just single neurons.
- Loss of nerve conductivity, which is the primary cause of the symptoms of MS. The purpose of myelin is to maintain a very specific concentration of ions along the surface of neurons in order to facilitate electrical transmission. Without myelin, signals travel much slower or get impeded altogether.Demyelination is certainly responsible for the progressive nature of the symptoms of MS, and it is certainly caused (at least in part) by the inflammatory reaction which occurs during flare-ups.However, it is now understood that inflammatory mediators directly block conductivity during flare-ups by disrupting the ion concentrations along the length of myelinated nerves, in addition to indirectly reducing conductivity via demyelination.
During an inflammatory response, the blood-brain barrier (BBB) becomes porous. The BBB provides an impenetrable layer of separation between the blood that circulates through our entire body and our brain. It only allows specific molecules and proteins to pass from the blood into the brain, like water and oxygen. During inflammatory flare-ups of MS, the BBB allows T cells and macrophages to infiltrate the brain. This rapidly accelerates progression of the disease and leads to increased demyelination and more severe flare-ups.
Diagnosis and characteristics of multiple sclerosis
Multiple sclerosis is diagnosed clinically based on symptoms, and medical imaging is used to verify the diagnosis. Greater than 95% of patients demonstrate visible white matter lesions on MRI scans.
The pathology of MS is generally accepted to be the presence of glial scars (scleroses) disseminated over both time and space. If a patient has had multiple attacks or flare-ups (disseminated over time), then a clinical diagnosis is sufficient. If a patient is seeking diagnosis after only one attack, then the presence of multiple white matter lesions (disseminated in space) is also necessary for definitive diagnosis.
Furthermore, multiple sclerosis is the only inflammatory demyelinating disease of the central nervous system (IDD) that causes subpial demyelination (subpial = the “noodle” of the brain immediately below the pia mater, which separates the brain from the skull). Multiple sclerosis is the only condition known to the medical community to cause subpial lesions.
Current treatment options and best practices for multiple sclerosis
Currently, there is no cure for MS. Medications approved for treatment of MS only serve to slow progression of the disease or to limit the severity of flare-ups when they occur.
Biologic drugs which modify the immune system’s signalling and genetic instructions are useful for reducing the severity of flare-ups, but they bring their own list of adverse reactions including an increased likelihood of developing cancer and a decreased immunity to even basic infections.
Many people have found cannabis to be a useful supplement in the management of multiple sclerosis and its symptoms. This has lead to research on the specific target of cannabinoids within the pathology of multiple sclerosis, and what that target can teach us about the disease itself.
Is endocannabinoid deficiency involved in multiple sclerosis?
The endocannabinoid system (ECS) is a regulatory mechanism in mammals that controls hundreds of biological processes from body temperature to nerve sensitivity to the contractions of digestive muscles. One of the roles of the ECS is in the regulation and maintenance of the immune system.
The ECS is comprised of receptors embedded in the membranes of our cells. When these receptors are activated by endocannabinoids or phytocannabinoids, they tell the cell to reduce its energy consumption and decrease its activity level – to put it simply. By controlling the activity of our cells, the ECS is responsible for maintaining homeostasis.
When the ECS becomes deficient or dysfunctional, the cells that its supposed to be regulating no longer do what our body needs them to be doing. In the brain, the immune system is represented by glial cells, cells located between and around our neurons that provide physical support and maintenance.
Glial cells, like other immune system cells, have the ability to become “activated” by injury, infection, or cell damage. Normal glial cells in their resting state do not express cannabinoid receptors. However, once activated, certain glial cells known as microglia begin to express cannabinoid CB2 receptors as a negative feedback mechanism to mediate the eventual deactivation of the cell following the immune reaction which activated it.
In multiple sclerosis, the inflammatory action of microglia is responsible for both the initial demyelination that leads to scarring, and the further recruitment of T-cells and macrophages which produce the progression of the disease. Loss of regulation of immune cells in patients with multiple sclerosis as a whole, and specifically during flare-ups, is a key factor in the dysfunction that leads to autoimmune reactions with such detrimental consequences.
Whether the appearance of cannabinoid receptors is necessary for the initial activation of microglia, or is a result of that activation, is still unknown. Cannabinoid receptors are known to regulate gene expression, especially in the immune system. It is possible that the abnormal expression of cannabinoid receptors in otherwise healthy glial cells could contribute to a change in their underlying activity and gene expression that leads to an autoimmune attack on certain areas of white matter.
Does CBD improve cases of multiple sclerosis?
CBD, and cannabis in general, have been known to improve cases of multiple sclerosis for some time now. The expression patterns and functionality of cannabinoid receptors in immunological tissue is well understood, and several idiopathic inflammatory diseases, including Crohn’s disease and rheumatism, are correlated with significant endocannabinoid system phenotypic abnormalities.
It is natural to postulate that the activity of phytocannabinoids on cannabinoid receptors expressed by cells of the immune system is responsible for the association of cannabinoids with improvements in cases of MS, including increased duration of periods of remittance, decreased severity of periods of relapse, and overall slowing of the progression of the disease.
Immune system effects of CBD for multiple sclerosis
Specifically, multiple sclerosis is noted by researchers for a change in the ratio of “killer” immune cells to “repair” immune cells. Targeting of cannabinoid receptors has shown to decrease cell migration, increase proliferation of anti-inflammatory factors, and decrease release of free radicals and ROS (reactive oxygen species) which degrade cell membranes and cause cell death – free radicals and ROS are how the immune system “kills” cells.
Moreover, CBD is known to reduce permeability of the blood brain barrier, which is a major component of MS. When immune cells native to the brain initiate an inflammatory response, the barrier separating the brain from the rest of the body becomes porous, allowing much more destructive immune mediators to enter brain tissue.
Antioxidant properties of cannabinoids for multiple sclerosis
Finally, CBD is a good representative of the neuroprotective properties exhibited by a number of other cannabinoids as well. Cannabinoids are potent antioxidants, which means they readily absorb free radicals and reactive oxygen species (ROS). Radicals and ROS are highly destructive molecules containing oxygen, and they breakdown both DNA and cell membranes with ease. They are also the primary mediators of cell death by the immune system, and they are the specific molecules that degrade myelin, producing the symptoms of MS.
In addition to directly eliminating free radicals and ROS thanks to potent antioxidant activity, CBD is uniquely able to activate PPARγ receptors and increase the production of our body’s own antioxidant army.
Is CBD a miracle for multiple sclerosis?
By limiting perforation of the blood-brain barrier, along with stimulating immune cells to favor reparation of damage as opposed to eradication of viable tissue, CBD can significantly impede the progression of multiple sclerosis because it reduces the frequency and severity of flare-ups.
CBD is known to improve the quality of life of individuals managing their condition, and ultimately it will lead to a deeper understanding of the pathogenesis of multiple sclerosis. If we can understand the root cause of MS, then maybe we’ll be able to prevent it from occurring in the first place.