Neuromuscular junction:

The neuromuscular junction (NMJ) is a highly specialized synapse between a motor neuron nerve terminal and its muscle fibre that is responsible for converting electrical impulses generated by the motor neuron into electrical activity in the muscle fibres.

Main Types of Muscle Diseases

Inflammatory Diseases:

• People get trichinosis when they eat undercooked meat — such as pork, bear, walrus, or horse — that is infected with the immature form (larvae) of the trichinella roundworm. In nature, animals are infected when they feed on other infected animals. It is a parasitic disease caused by a capillary worm common in uncooked pork.

• Myositis: Inflammation of muscle tissue.

• Polymyositis: Multi-muscular inflammation whose causes are unknown.

Eclipse Diseases (Structural Impairment):

• McArdle disease is caused by impairment that prevents lactic acid from being exploited. It is a type of glycogen storage disease. It results from a lack of a key substance that the muscles need to break down glycogen into sugar (glucose) for energy. The condition causes tiredness and muscle pain during exercise. The disease can lead to dark urine.

• Duchenne disease: Duchenne muscular dystrophy

• Sarcopenia, a depletion of the skeletal muscle, is a decrease in the mass and strength of the skeletal muscles. Usually occurs in post-middle age and more in men than in women. The result of skeletal muscle depletion is limitations in functioning, an increase in the risk of falls, and also bone fractures and exhaustion.

Muscle Pain – How do they appear and what causes them?

Muscle pain is a fairly common phenomenon that characterizes almost every person during his adult life. They have several common forms that describe the appearance of muscle pain.

Muscle pain that appears simplified throughout the body

Viral-infectious diseases, systemic joint diseases and especially multi-rheumatoid muscle pain, inflammatory muscle diseases, non-inflammatory diseases such as muscular dystrophy, metabolic diseases, vitamin D deficiency, vitamin C deficiency, mitochondrial diseases, hereditary diseases, chronic diseases, hormonal diseases, hypothyroidism, adrenal insufficiency, side effects from medications such as Statins (lowering cholesterol levels), Psychiatric disorders.

Muscle pain that attacks a specific area, defined and clear

Among the causes of the pain are strenuous physical activity, local inflammatory conditions such as inflammation (Bursitis, and muscular ischemia that may reach the point of infarction in the muscle.

CBD as a treatment of Muscle Pain

There is a hypothesis that a high-fat diet (HFD) disrupts the Endocannabinoid System (ECS) and affects muscle cell activity by blocking CB1 receptors, thus affecting both the genes involved in lipid metabolism and the endocannabinoid system.

The ECS plays an important role in the onset of obesity and metabolic disorders, implicating central and peripheral mechanisms predominantly via cannabinoid type 1 (CB1) receptors. CB1 receptor antagonist/inverse agonist treatment improves cardiometabolic risk factors and insulin resistance. However, the relative contribution of peripheral organs to the net beneficial metabolic effects remains unclear. Recent studies have identified the presence of the endocannabinoid signalling machinery in skeletal muscle and also investigated the impact of an HFD (high-fat diet) on lipid-metabolism-related genes and endocannabinoid-related proteins.
In conclusion, the results of the study indicate a diet-sensitive ECS in skeletal muscle, suggesting that blockade of CB1 receptors could work towards the restoration of the metabolic adaptation imposed by diet.

A recent study examined the ability of a CB1R inverse agonist – AM-251 (Rimonabant analogue), to repair the damage to muscle cells induced by obesity. The results confirm that as a result of eating oily food, there are changes in the endocannabinoid system. Treatment with the CB1 antagonist may return lipid metabolism in muscles to the normal (non-obese) state.

• Expression of the cannabinoid system in muscle: Effects of a high-fat diet and CB1 receptor blockade.

• Effects of non-euphoric plant cannabinoids on muscle quality and performance of dystrophic MDX mice.

• Click here for more details about CBD

Muscle diseases that can be treated with CBD:

Severe Muscle Spasm, Muscle Tone Disorder, Multiple Sclerosis (MS)

About 90% of patients with MS suffer from spasticity. Some feel itching and tingling nonstop muscle spasms or involuntary seizures. Muscle spasms are weakening and painful, they undermine freedom of movement, disrupt daily routines, and impair the quality of sleep. Sometimes the spasms cause paralysis. For years, the treatment for MS was focused on trying to calm the typical muscle spasm caused by the disease.

CBD as a treatment of Muscle Spasticity

Over the past 20 years, dozens of studies have been conducted on the mechanisms of action of CBD in the treatment of mice that have experimental MS and the findings are unequivocal. Today, it is clear that cannabidiol has proven potential in calming muscle spasms at the molecular level – the path to clinical trials in humans has opened up.

• Medical Marijuana (Cannabis) FAQs.

• Marijuana And Muscle Spasticity.

Fibromyalgia (Muscular Dystrophy)

The main symptoms of fibromyalgia are severe striated muscle pain in many areas of the body, painful sensitivity in pressing palpitation at certain points (tender points), usually symmetry, in the body, certain stasis in movements in the mornings, spontaneous sensations of tingling, sometimes described as “needles and pins”. These are symptoms of partial damage to the peripheral nerve, plus related symptoms such as non-refreshing sleep, fatigue, attention deficit disorders, and low willpower.

The disorder is sometimes accompanied by inflammatory joint diseases. It is not characterized by signs of inflammation and should be differentiated from rheumatoid arthritis [RA].

CBD as a Fibromyalgia treatment

In 2011, the United States carried out a first controlled study on women with fibromyalgia with the help of medical cannabis. A group of several dozen women took medical marijuana and a placebo drug for several weeks. Since marijuana was given in smoking, it can be assumed that the patients felt the placebo. At the same time, the results were extremely positive.

Although they represented a large variety of pain strengths and related symptoms, the patients who received medical marijuana reported significant improvements in symptoms, relieving muscle pain, better sleep, and pain-free joint movement.

• The Consumption of Cannabis by Fibromyalgia Patients in Israel.
• Cannabis Use in Patients with Fibromyalgia: Effect on Symptoms Relief and Health-Related Quality of Life.
• The Relationship of Endocannabinoidome Lipid Mediators With Pain and Psychological Stress in Women With Fibromyalgia: A Case-Control Study.
• Cannabinoids for fibromyalgia

Myopathy

There are a variety of diseases that damage the muscles (myo=muscle). The muscles of the limbs, the pelvis, the back, the face, the breathing, and more. Causes of myopathy are:

1. Hereditary diseases that are caused by a genetic defect in one of the muscle components, also called muscular dystrophy.

2. Inflammatory reaction.

3. Side effects of medications, exposure to toxic substances, nutritional deficiencies such as magnesium, and more.

4. Complication of other diseases, especially metabolic and endocrine diseases.

The main symptoms of myopathy are weakness and depletion of muscle mass

Usually, the large muscles are damaged: The muscles of the belts of the shoulders and pelvis, neck, and thighs, although any voluntary muscle may be damaged depending on what type of myopathy it is. There are types of myopathy in which the defect is in the energy pathways inside the muscle, and then the main manifestation will be the appearance of pain when performing a physical exercise and difficulty continuing the activity. Muscle weakness is manifested in difficulty and weakness inactivity such as lifting loads, carrying objects, raising hands, combing hair, getting up from sitting, walking, climbing stairs, etc.

Muscular dystrophy or muscular depletion

(from Greek, Sarcopenia, which means “poverty of meat”) is a condition that manifests itself in the loss of skeletal muscle mass as part of the ageing process. Over the age of 50, the human body loses between 0.5-1% of skeletal muscle mass each year. Muscular dystrophy is not a disease or a clear syndrome and the boundary between normal (physiological) muscular dystrophy versus abnormal (pathological) muscular dystrophy is unclear.

CBD as a treatment of Myopathy

CBD treatment causes a benefit in myopathy symptoms due to the control of the release of neurotransmitters, soothing inflammation, and pain relief. 1977 (!) study found that mice with induced muscular dystrophy showed improvement in symptoms after receiving treatment by THC and CBD.

Muscular dystrophy in mice after chronic subcutaneous treatment with cannabinoids

Motor Neuron Disease (MND) Amyotrophic Lateral Sclerosis (ALS)

This disease damages the peripheral motor neurons through which the brain monitors the activation of most of the striated muscles in the body. Neurons are destroyed and as a result, they cannot activate the muscles, causing them to weaken until they are completely paralyzed. During the disease, the muscles responsible for activating the extremities, swallowing, speaking, and breathing are gradually damaged.

CBD as a treatment of ALS disease

Damage to the cells of the nervous system in ALS is caused by two main factors: oxidative stress and toxicity (excitotoxicity) of the excitatory neural messenger – Glutamate. Oxidative stress occurs when there is an imbalance between reactive free radicals [ROS] and antioxidants. When there is a decrease in the production of internal antioxidants (such as Glutathione), it is difficult for the body to catch up with the rate of production of free radicals, thus the body has difficulty protecting itself from the damage caused to the cells of the central nervous system, and from the destructive effects associated with oxidative stress. The cannabis plant is a well-known antioxidant and is the main feature in which it helps treat and rehabilitate damaged tissues. Toxicity of the excitotoxicity neurotransmitter messengers (Glu) destroys cells in tissues that are already damaged by oxidative processes or inflammation. When nerve tissue is damaged, the amino acid glutamate is released excessively in an uncontrolled manner. Uncontrolled release of Glu leads to cell destruction and death. Early studies on the cannabis plant have shown that CBD and THC lower the level of glutamate and thus protect the destruction of nervous system cells. In 2004, a study was conducted in which THC was found to inhibit the development of experimental ALS in mice. Based on these findings, patients suffering from the disease began to experience medical cannabis self-treatment and in recent years have focused on CBD-rich strains. Reports suggest that CBD relieves muscle pain, expands bronchial and trachea, reduces saliva build-up, encourages appetite, and balances sleep.

Read more about CBD as an antioxidant.

Relevant links:

• CBD relieves the symptoms of ALS.

• ALS & CANNABINOIDS: CBD and THC may help ALS patients manage symptoms and increase life expectancy.

• Cannabis and Amyotrophic Lateral Sclerosis: Hypothetical and practical applications, and a call for clinical trials.

• Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?

A recent 2019 study demonstrates the safety of the drug – Nabiximols better known as “Sativex” (THC: CBD 1:1) for patients suffering from ALS. The study examined the effect of the drug and its possible side effects after a few months. The study was carried out on dozens of volunteer patients and the results show a reduction of the tremors characteristic of the disease.

Additional myopathies where CBD may be used as an effective treatment

CBD helps calm inflammation and relieves pain. The muscle cramps characteristic of many muscle diseases may be caused by inflammation. The second way to treat cramps and muscle pain is simply to soothe the feeling of pain. Cannabidiol has a proven ability as a strong and good painkiller with major advantages. There is no need to increase the dose or fear dependence and side effects. Acting on immune cells may help in cases where muscle disease is an immune disease and here too CBD may help with its diverse properties. Due to the sweeping prohibition on cannabinoid research in recent decades, it was not possible to carry out an orderly clinical study involving as large groups as possible, using a Placebo drug as control, cross-referencing treatments, and double-blind experiments. In countries like Canada, clinical studies have begun in the past few years and the results are encouraging. The CBD products market is currently opening in many countries allowing many consumers to experiment with self-treatment and share results.

Hereditary myopathies

Hereditary myopathy is caused by a genetic defect in one of the muscle components and is also called muscular dystrophy. The hereditary myopathic group contains several types of inherited diseases, with a larger group than these being a group called Muscular dystrophies. This group is characterized by progressive muscle weakness and muscle depletion.

Neuropathy

Peripheral neuropathy, often shortened to neuropathy, is a general term describing a disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or organ function depending on which nerves are affected; Neuropathy affecting motor, sensory, or autonomic nerves result in different symptoms. More than one type of nerve may be affected simultaneously. Peripheral neuropathy may be acute (with sudden onset, rapid progress) or chronic (symptoms begin subtly and progress slowly), and maybe reversible or permanent.

Diabetic neuropathy, inflammatory neuropathies (such as CIDP and Guillain Barre Syndrome) include diseases of the peripheral nerves, diseases of nerve-muscle connection, and muscle diseases. One of the most common causes of impairment of muscle activity is a disease of the nervous system. Since the nervous system is responsible for muscle activation, damaging it will disrupt muscle function. Stroke, for example, often leads to paralysis of both a hand and a leg. Diseases throughout the trajectory of the transmission of the neural signal (brain, spinal cord, neural extensions, nerve cell) can damage the muscle. Neuropathy is usually manifested in sensational disorders in the extremities, such as Circumcision, numbness, burning sensation, feeling of, feeling as if stepping on stones, and more, as well as weakness mainly in the muscles of the hands and feet.

Myasthenia Gravis (MG)

Characterized by the weakness of the limb muscles, weakness of the facial muscles: eyelid prolapse, change in sound tone, difficulty speaking and swallowing, and more. Myasthenia Gravis is due to the binding of autoimmune antibodies against the components of the nervous system – the nerve receptors for the neurotransmitter acetylcholine (Ach) in the postsynaptic membrane of the nerve-muscle connection. As a result, the muscle weakness often develops, involving the eyelids, swallowing muscles, respiratory muscles, and limb muscles.

Duchenne Muscular Dystrophy of Duchenne Dystrophy

A group of hereditary diseases, usually appearing at a young age, in which an advanced weakness of the muscular system appears, which can lead to confinement to a wheelchair and respiratory failure. Known for these diseases is Duchenne muscular dystrophy. It is the most common form of muscular dystrophy disease. The disease is inherited by linking onto the x chromosome, and therefore the disease mainly harms males. Symptoms of the disease begin at the age of five, and in adulthood, the patients are severely restricted and usually die in the third decade of their lives.

Becker Dystrophy MG

A disease transmitted in the link of the x chromosome, causing muscle weakness similar to Duchenne disease. The mortality age is on average at 42. This disease causes no heart damage and no mental retardation.

Emery-Dreifuss Muscular Dystrophy

Most often the disease is transmitted in a link on the x chromosome, but it can rarely pass through autosomal (recessive or dominant) inheritance. The disease begins in childhood and progresses slowly while creating weakness and depletion, mainly of muscles such as the triceps and biceps muscle in the hands, as well as muscles in the shin such as the anterior tibialis muscle. In this disease, there are simultaneously disorders in the heart as well as cardiomyopathy (destruction of the heart muscle).

Limb-Girdle Dystrophy

It is a recessive autosomal disease, which begins between late childhood and early adulthood. Unlike Duchenne disease, in this disease, the shoulder belt, and pelvic belt are affected almost evenly.

GNE Myopathy

Recessive hereditary disease is caused by a mutation in the GNE gene that is common in Jews of Persian and Japanese origin (also called Nonaka myopathy). The disease is characterized by damage to the distal muscles (in the hands or legs). The disease is characterized by a lack of damage to the quadriceps muscle.

Facioscapulohumeral Dystrophy

A dominant autosomal disease that begins with puberty and manifests itself in the clinic with varying severity. The muscle weakness is usually limited to the face, neck, and shoulder belt, but can also appear in other muscles. It is common to see this condition as an injury to a scapula called a “Winged scapula”.

Distal Myopathy

A dominant autosomal disease that appears after the age of 40, involving the small muscles of the hands and feet & palm. The course of the disease is progressing slowly.

Ocular Dystrophy

A dominant autosomal disease that also exists in the form of recessive inheritance, but is also sporadically not linked to heredity. The onset of the disease is usually before the age of 30, the initial manifestation is eyelid prolapse (“pathosis”), after which progressive external ophthalmoplegia develops, that is, paralysis of eye movements that deteriorates, facial weakness is also common. The course of the disease is progressing slowly.

Oculopharyngeal Dystrophy

A dominant autosomal disease, starting between a third and fifth decade in life. Clinical symptoms include: eyelid prolapse, general external ophthalepolphilia, difficulty swallowing that requires feeding the patient in Zonda, or gastrostomy.

Inflammatory myopathy

Acquired myopathy is often caused by an inflammatory process in the muscles, that is, an autoimmune disease in which the immune system attacks the muscle cells. In these cases, it is an autoimmune disease, which can damage not only muscles but other organs as well. Several myopathies are caused by an inflammatory or autoimmune disease.

Polymyositis

It is a disease characterized by the destruction of muscle fibres and the inflammatory incitement of muscles. The disease can appear at any age, progressing at a variable rate and causing weakness and muscle depletion, especially of the shoulder belt muscles and proximal limbs. The disease is often associated with muscle pain, sensitivity, difficulty swallowing, and difficulty breathing. Rhino phenomenon, joint pain, weight loss, and sometimes low fever also appear. Pathologically, this disease is characterized by cytotoxic-tux cells that invade muscle fibres and cause necrosis. Treatment is the provision of anti-inflammatory drugs such as steroids (prednisone mainly), as well as immune-suppressing drugs such as IVIG, methotrexate, and Imuran.

Dermatomyositis

It is a disease similar to polymyositis but is also characterized by an erythematous rash around the eyelids, above the eyes, or in different areas on the wrists. Pathologically the disease is caused by the destruction of intramural capillaries (in the endomysium of the muscle) by over-activating the complement system. As a result, muscle ischemia is caused. There is a clear parallel between dermatomyositis that begins in old age and cancer. The drug treatment of this disease is similar to the drug treatment of polymyositis.

Myositis with inclusion bodies, Inclusion body myositis

This disorder is more common in men, which usually begins after the age of 50. The disease is described as a proximal weakness of the lower extremities and then upper limbs. The disease is progressive, and sometimes there may also be a distal weakness, but it is less pronounced than the proximal weakness. The cause of the disease is unknown, but it is known to involve T cells that damage the muscle and probably have some hereditary component. This disease is sometimes accompanied by various disorders such as diabetes or peripheral neuropathy. Copper levels can be high or normal. The diagnosis is by taking a cytology test. This disorder does not respond to immunosuppressive therapy (unlike dermatomyositis or polymyositis).

Secondary Muscle Diseases

Myopathic due to medications – muscle diseases can appear following medical treatment. One of the most common causes of muscle damage today is the taking of cholesterol-reducing drugs – Statins. These drugs are very effective in reducing blood cholesterol but cause muscle pain, and in extreme situations also the destruction of the actual muscle fibres. Alcohol can also impair muscle activity, as well as an abnormal increase in thyroid activity.

Myopathy can be caused by steroid use, (chloroquine), colchicine, statins, and some other medications. Symptoms range from the rise of Creatine Kinase (CK) enzymes without accompanying signs to acute and potentially life-threatening rhabdomyolysis. Myopathy that causes muscle necrosis and rhabdomyolysis are mainly due to the use of Statin-lowering drugs while mitochondrial myopathies are mainly due to the use of antiretroviral drugs. These myopathies are usually reversible when discontinuing the use of the toxic drug.

Metabolic and Endocrine myopathies

There are several metabolic and endocrine conditions related to myopathy:

Chronic hypokalemia: A chronic condition (reduced potassium in the blood) that can cause proximal myopathy. It is a reversible condition that improves within weeks with the repair of the potassium balance.

Syndromes related to periodic paralysis syndromes

These are syndromes that can be familial and are characterized by episodes of placid muscle weakness or muscle paralysis, associated with abnormality at the level of potassium in plasma. Between seizures, the muscle force is reserved.

There are three main forms

1. Hypokalemia-related syndrome, in which attacks tend to appear in wakefulness, after excrementing, or after a heavy meal, and can last several days.

2. There is a hyperkalemic form in which seizures appear after an effort but are shorter and last less than an hour.

3. There is a normal-kalemia form, which sometimes does not respond to treatment.

Other conditions related to myopathy include Osteomalacia, hypothyroidism, hypothyroidism as well as acromegaly.

Other muscle diseases where CBD may serve as an effective treatment

• Infectious muscle diseases: Infectious diseases of the muscle, caused by bacteria or viruses, are quite rare.

• Malignant diseases of the muscle: This disease is quite rare. Muscle cell cancer is called rhabdomyosarcoma, and its treatment mainly includes surgical removal.

• Trauma and muscle injuries: Traumatic injuries are not diseases of the muscle, but they are quite common. A muscle injury can appear after a car accident, fall from a height.

• Myotonia: Diseases that cause muscle spasms.

• Bursitis: bursae is a pad filled with watery fluid that acts like a pillow and softens the contact between tendons and muscles and bones usually in the joint region. When an inflammation appears in the lid there is a feeling of pain in the area and even a restriction in movement. The most common places for the appearance of inflammation in the lid are the joints of the shoulder, elbow, and hip. However, it can also appear in the knee, ankle, and toe bases. The inflammations usually appear in joints that perform a constant repetitive movement over time.