Introduction

Multiple Sclerosis (MS) is a type 4 hypersensitivity chronic autoimmune disease that affects the central nervous system, resulting from damage in the protective covering of nerve fibers, known as myelin affecting signal transmission to and from the brain. It can cause problems with the brain, spinal cord and optic nerves as a result, patient may start experiencing blurred vision, have difficulty walking, easily tired fatigue, can even feel tingling sensation and numbness, and other neurological symoptoms.

In addition to these symptoms, is heat sensitivity, with a prevalence of 60-80% in the approximately 2.3 million people around the globe affected by Multiple Sclerosis. As MS progresses, manyother symptoms can be increased when a patient is exposed to heat, making it difficult to perform even daily tasks.

The goal for therapy for individuals with MS is to relieve symptoms. How does Multiple Sclerosis develop?

While the causes of MS are unknown, there are potential environmental and genetic factors that can trigger the occurrence of MS. Factors such as smoking, vitamin D deficiency, inflammatory bowel disease, Human Herpes Virus, being a female between the ages of 20-40, certain autoimmune disorders like thyroid disease, psoriasis, type 1 diabetes, etc, and the Epstein-Barr virus.

When an individual is exposed to any of the molecules of the precipitating factors (antigen), it is engulfed by an antigen-presenting cell, which now expresses a piece of the antigen on its surface (Major Histocompatibility Complex class II - MHC II). The expressed antigen forms a complex with the MHC-II. The complex is presented to a Helper T-cell which has a type of receptor that can recognise the antigen. With this exposure of the helper T-cell to the antigen, the helper T-cell is now a primed cell and can recognise the antigen or any of its lookalike molecules. 

In the case of another exposure to this antigen, the primed T-cells find their way across the blood brain barrier (BBB) by attaching themselves to adhesion molecules causing the breakdown of the blood-brain barrier. The BBB is made up of the endothelial lining, pericytes (PCs), capillary basement membrane, and astrocytes, making it selectively permeable. Once the primed T-cells get through the BBB, it travels to the neural tissue and the neurons wrapped around by a protective sheath called myelin sheath. 

The molecules of the myelinated sheath on the axons in the central nervous system, can resemble some of the molecules of any of these antigens. So, these T-cells mistake protein molecules of the myelin sheath as an antigen and stick to it. This adhering activates the T cells causing them to release cytokines. 

These cytokines are the Interleukin-I, Interleukin-VI and the Tumor necrotic factor alpha. They perform the following;

1. Increase adhesion markers on the endothelial lining of the BBB to enable more T cells to cross
2. They trigger vasodilation leading to more blood flow through the BBB, making more white blood cells cross the BBB to the adhered axons
3. Activate the release of Interferon alpha (IFN- alpha) which stimulates and activates macrophages, causing them to migrate to the adhered neuron
4. The white blood cells that crossed the BBB get converted into antibodies-producing cells called Plasma cells. These cells produce antibodies once they adhere to axon
5. The macrophages get attracted to the antibodies produced by the antibody-producing cells and since the antibodies are pegged on the axon, the macrophages in turn feeds on the axon whilst feeding on the antibodies
6. Continuous feeding on the axon, strips off its myelin sheath, causing scars. These scars form plaques/sclera on the axon. As these sclera are formed on multiple points on the axon, they are called MULTIPLE SCLEROSIS⁹ 

Symptoms of Multiple Sclerosis

Multiple Sclerosis damages the protective covering of the axon affecting signal transmission to and from the brain causing symptoms like: 

• Pain
• Tiredness
• Vision loss
• Heat sensitivity 
• Numbness and Tingling
• Weakness and spasticity
• Difficulty in processing information 

Pain 

To make up for the affected tissues, the unaffected muscles are overused resulting in pain. This pain can occur in hips, legs, arms, face, the back of the head, down the spine, and eyes. The pain can become chronic. 

Tiredness

Because the unaffected muscles are overused, there is increased energy use. It can lead to constant tiredness and exhaustion.

Vision loss

The part of the human body responsible for vision lies in the brain. It is known as the vision centre. To get this vision centre to transmit images, the eyes have to transmit signals from the retina through the optic nerve.

MS can cause damage to the nerves which transmit visual information from the eyes to the brain, resulting in optic neuritis, causing vision loss, or pain when moving the eyes.

Numbness and tingling

Pressure on a nerve as a result of inflammation or injury can cause tingling sensation in the feet or hands referred to as ‘pins and needles.’ For numbness, there is loss of or diminished sensation. It can be experienced on the face, body or legs. You may notice this when you barely feel anything when you come in contact with something. In some people, either tingling or numbness occurs; in others, both can occur. 

Difficulty processing information

The BBB protects the brain from harmful substances by acting as a filter. When it becomes porous to T cells, and the myelin sheath of the axon in the white matter of the brain - which is rich in myelinated axons- gets damaged, cognitive function becomes compromised. This can lead to memory problems, attention deficits, and difficulty in processing information. 

Heat sensitivity

Heat sensitivity is a common symptom for many individuals living with Multiple Sclerosis (MS). It impacts their routines because, when there is a slight increase in body temperature,due to factors such as hot weather, exercise, or fever, other symptoms worsen. This is known as Uhthoff’s phenomenon.

Heat sensitivity in MS Patients

Heat sensitivity in MS patients is the result of an inability of the nervous system to respond to changes in temperatures. The central nervous system relies on electrical signals for communication, and in MS, where the myelin (the protective sheath around nerves)is damaged, these signals can be delayed or distorted. When the body is exposed to heat, these signals may become further disrupted, exacerbating existing symptoms or causing new ones to emerge.

For MS patients, heat sensitivity can worsen symptoms such as muscle weakness, fatigue, and cognitive dysfunction. The impact can be temporary, lasting only as long as the heat exposure, but for some, it can be frequent.

Common triggers and symptoms

Several factors can trigger heat sensitivity in MS patients, and these can include environmental factors, physical exertion, and even emotional stress. Common triggers include:

• Illness
• Stress
• Hot bath
• Warm weather
• Physical activities

Illness 

When a person with MS falls ill, the body’s temperature is altered, causing MS symptoms to flare up.

Stress

Emotional responses can also increase body temperature and trigger symptoms of heat sensitivity.

Hot bath

Getting immersed in warm water can raise body temperature quickly, triggering symptoms.

Warm weather

When there is exposure to hot or humid weather, the body’s temperature can increase, leading to an increase of MS symptoms.

Physical activities

Exercise or strenuous activities that cause the body’s temperature to increase. This can worsen symptoms, such as muscle weakness, spasms, and balance problems.

The impact of heat sensitivity on daily life

Simple tasks such as walking, exercise, or even spending time outside can become difficult. With these effects, social interactions, family activities, and work life can be affected, as heat sensitivity can limit participation in outdoor events or physical activities. This limitation can lead to feelings of isolation, frustration, and a reduced sense of independence.

It is also important to note that chronic heat sensitivity may worsen the already-present fatigue and other neurological symptoms associated with MS, leading to a diminished quality of life.

To reduce the impact of heat sensitivity, people living with MS need to limit their exposure to hot environments or take precautions to avoid overheating. However, it is worth to note that the need to stay in a cool environment may contribute to a sedentary lifestyle, which can have secondary effects like muscle atrophy and further loss of mobility. 

Cannabis and cannabinoids

Cannabis is a herb with three major species: C. sativa, C.ruderalis, C. indica. It contains over 80 distinct molecules that bind and activate the cannabinoid receptors CB1 (mostly found in the central nervous system) and CB2 (mostly found in the immune system cells.) These molecules are collectively called Cannabinoids. 

The cannabinoid receptors are a part of the endocannabinoid system- a system responsible for regulating stress response, anxiety, memory, pain, and motivated behavior across the lifespan. It performs this by interacting with neurotransmitters and influencing their effects as signals are transmitted.

The main cannabinoids in Cannabis are Delta-9-tetrahydrocannabinol (THC) and CBD (cannabidiol). Delta-9-tetrahydrocannabinol (THC) is the main psychoactive substance found in Cannabis sativa and when in high quantity, exerts psychoactive effect. 

Cannabinoids, the active compounds found in cannabis, have shown promise in alleviating a range of MS symptoms, including heat sensitivity. Cannabinoids exert their effects by interacting with the body’s endocannabinoid system, which plays a critical role in regulating various physiological functions, including temperature regulation, pain perception, and inflammation.

The role of cannabis in managing heat sensitivity

While research specifically addressing the relationship between cannabis and heat sensitivity in MS is limited, cannabinoids exert their effects primarily through the Endocannabinoid system (ECS), which helps regulate a range of physiological processes, including temperature control. Cannabis may modulate the body's thermoregulatory mechanisms by interacting with cannabinoid receptors, potentially helping to alleviate the worsening of MS symptoms triggered by heat. THC, in particular, has been shown to have a vasodilatory effect, which could assist in dissipating heat from the body and preventing overheating in individuals with MS.

Studies have also examined Cannabis’s anti-inflammatory properties that may play a key role in reducing heat sensitivity. By reducing inflammatory markers and immune responses, cannabinoids may mitigate the inflammatory cascade that worsens MS symptoms during heat exposure.

Other potential roles of cannabinoids for MS patients are;

Pain relief

Chronic pain is common in MS. Cannabinoids such as THC (tetrahydrocannabinol) and CBD (cannabidiol) act as adjuvants in the treatment of pain. They interact with the endocannabinoid system (ECS), a regulatory system that plays a role in pain perception. The ECS modulates pain through its receptors, primarily CB1 and CB2, which are found in the brain, spinal cord, and peripheral nerves.

When CB1 receptors are activated by the effect of cannabinoids, there is decrease in presynaptic neuron firing, resulting in reducedin neurotransmitter release responsible for pain causing relief from pain. 

Muscle spasticity

Involuntary muscle contractions and stiffness is another symptom of MS. It can affect mobility and increase the risk of falls. Traditional treatments for spasticity, such as muscle relaxants and physical therapy, may provide limited relief. In recent years, cannabis has emerged as a potential therapy for managing spasticity. Research has shown that cannabinoids can reduce muscle stiffness by modulating motor control pathways and influencing neurotransmitter release. 

Neuroprotective properties

Beyond pain and spasticity management, cannabis may offer neuroprotective benefits for MS patients. Neuroinflammation is an indication of MS progression, leading to neuronal damage and loss of the myelin sheath. Cannabinoids, particularly CBD, have the ability to reduce inflammation and oxidative stress, protecting the neurons from further damage.

Risks of cannabis use for heat sensitivity in MS patients

Despite the potential benefits, cannabis use is not without risks. THC, in particular, can cause cognitive impairment, dizziness, and mood alterations, which may be problematic for MS patients already dealing with cognitive challenges. Additionally, long-term use of cannabis may lead to dependency or exacerbate psychiatric symptoms in vulnerable individuals. Therefore, it is important for patients to consult with healthcare providers before incorporating cannabis into their symptom management plan.

Summary

Long-term cannabis use also carries the risk of dependency. Therefore, it is important for patients to consult healthcare professionals before using cannabis as a treatment for heat sensitivity and other MS-related symptoms.