Muscular dystrophy (MD) presents a unique set of challenges to modern medicine. Chronic pain, muscle spasms and limitations in daily living and can be debilitating. While there is no cure for MD, new treatments for symptom management are emerging. Researchers have been actively exploring how medical cannabis can improve the quality of life for people with muscular dystrophy (MD).


Understanding Muscular Atrophy

Muscular dystrophy (MD) is a group of genetic disorders characterised by progressive muscle degeneration and weakness. This debilitating disease severely affects the quality of life of patients, resulting in widespread muscle weakness and difficulty in daily activities.

The first medical report of muscular dystrophy dates back to 1836, when Italian doctors Gaetano Conte and Luigi Gioja described the case of two brothers suffering from progressive muscle weakness. However, due to the very limited medical knowledge and diagnostic tools available at the time, the case was initially misinterpreted as tuberculosis by their contemporaries.

It was not until 1861 that French neurologist specialist Guillaume Duchenne recognised it as a distinct disease, later known as Duchenne muscular dystrophy. With the help of Dr Duchenne's meticulous records, a distinction was finally made between muscular dystrophy and other neuromuscular diseases. By 1868, Dr Duchenne had documented multiple cases and published detailed photographs, cementing the knowledge of this true disease.


Genetic Basis and Types of Muscular Atrophy

It has been found that muscular dystrophy is mainly caused by genetic mutations that impair the production and function of key muscle proteins and can lead to degeneration of muscle fibres, which can leave a person with weak and atrophied muscles. The mode of inheritance of these mutations may be autosomal dominant, autosomal recessive, or X-linked, and these factors determine how the disease manifests itself and how it is passed from generation to generation.

There are nine main types of muscular dystrophy, each with unique characteristics and varying degrees of severity:

1.Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in children, affecting about 1 in 3,500 to 5,000 baby boys worldwide. The disease is caused by a mutation in the gene for the muscular dystrophy protein on the X chromosome, resulting in a complete absence of the muscle dystrophy protein. This protein is essential for maintaining muscle cell integrity. Symptoms such as difficulty running, jumping and frequent falls usually appear between the ages of 2 and 5. As the disease progresses, patients usually lose the ability to walk in their teens and develop life-threatening complications in their 20s.

2. Becker muscular dystrophy (BMD) is similar to DMD but has milder symptoms and is caused by a mutation in the same gene. The condition produces a number of functional muscle atrophy proteins. Symptoms include muscle weakness and spasticity, which usually appear later in childhood or adolescence and progress more slowly. Patients may not require hospitalisation until their 30s.

3. Congenital Progressive Muscular Dystrophy (CMD) usually appears at birth or early infancy and is characterised by generalised muscle weakness, joint stiffness and spinal deformities. Some forms of CMD also involve brain abnormalities that can lead to mental retardation. CMD can affect both males and females, and its severity depends on the specific genetic mutation involved.

4. Distal muscular dystrophy mainly affects the muscles of the hands, forearms, feet and lower legs. The disease is caused by mutations in several different genes, resulting in progressive muscle weakness and difficulty in movement. Despite the degeneration of the muscles, these symptoms usually do not yet affect the patient's life expectancy.

5. Emery-Dreyfus muscular dystrophy is characterised by muscle weakness, tendon contractures and causes cardiomyopathy, which is caused by defects in the proteins surrounding the nucleus of the cells. Symptoms include difficulty in bending the neck forwards, difficulty in raising the arms and triggering heart complications that can lead to sudden death if not handled properly.

6. Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common symptoms of muscular dystrophy and affects both men and women. It involves muscle weakness and atrophy, especially in the face, shoulders and upper arms. Symptoms usually appear during adolescence or early adulthood. Although FSHD is debilitating, it usually does not affect the patient's life expectancy.

7. Limb-girdle muscular dystrophy affects the muscles around the hips and shoulders. It encompasses a wide range of rare disorders caused by mutations in different genes. Symptoms usually appear in adolescence or early adulthood, such as frequent falls and difficulty climbing stairs, and worsen over time.

8. Myotonic muscular atrophy is characterized by the inability of muscles to relax or prolonged muscle contraction and is one of the most common muscular dystrophies in adults. It is caused by mutations on chromosome 19 or chromosome 3. Symptoms include difficulty swallowing, fatigue, heart problems, and cataracts. The age of onset is typically between 20 and 30 years.

9. Oculopharyngeal muscular dystrophy affects mainly the muscles of the eyes and throat, resulting in weak drooping eyelids and difficulty swallowing from the throat. It is caused by an abnormal duplication of the GCG triad in the PABPN1 gene. This type of muscular dystrophy is usually found in specific groups of people, with symptoms typically appearing around the age of 60.


The Endocannabinoid System and Muscular Atrophy

The endocannabinoid system (ECS) is a complex network of receptors and signaling molecules that plays a crucial role in regulating various physiological processes, including muscle function. The ECS includes cannabinoid receptors (CB1 and CB2), endocannabinoids (such as anandamide and 2-arachidonoylglycerol (2-AG)), and the enzymes responsible for synthesizing and degrading these substances.

CB1 receptors are primarily found in the central nervous system but are also present in muscle tissues. These receptors help regulate muscle energy supply by influencing glucose and insulin metabolism. During exercise and muscle development, ECS activity changes, which may contribute to muscle growth and repair. Given this important role, targeting the ECS represents a promising approach for treating muscular atrophy.


The Potential of Medical Cannabis in Treating Muscular Atrophy

Due to the diverse and promising therapeutic properties of cannabinoids, medical cannabis is gaining attention for its potential in alleviating the symptoms of muscular atrophy. Research highlights the benefits of cannabinoids, such as tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabidivarin (CBDV), in relieving chronic pain, reducing muscle spasms, and improving overall muscle function.

Study Targets Duchenne Muscular Dystrophy

According to a study on Duchenne muscular dystrophy, there is an altered pattern of endogenous cannabinoid 2-AG expression and increased CB1 receptor expression in the muscles of Duchenne muscular dystrophy patients and animal models compared to healthy controls. This imbalance was associated with an increase in satellite cells, which are essential for muscle repair but can be harmful in excess.

Treatment with the CB1 receptor antagonist rimonabant reduces satellite cell proliferation and improves myofibre health by enhancing myotube formation. In animal models, the use of rimonabant prevented loss of muscle coordination and strength, which was attributed to reduced inflammation and improved muscle fibre integrity.


Cannabidiol (CBD) and Cannabidiol (CBDV)

Cannabidiol (CBD) and its derivative, hypocannabidiol (CBDV), have attracted considerable interest due to their potential therapeutic effects on Duchenne muscular dystrophy. Studies have shown that both CBD and CBDV promote the formation of myotubes in human muscle cells, which is essential for muscle growth and repair.

In an animal test model of Duchenne muscular dystrophy, treatment with CBD and CBDV improved motor activity, reduced inflammation and increased autophagy, a process that removes damaged cells and regenerates healthier ones. While THCV (Hypocannabinol) did not show the same efficacy in promoting myotube formation, the benefits observed from CBD and CBDV suggest that these cannabinoids may play a key role in controlling Duchenne muscular dystrophy and improving muscle function.


Medical Cannabis in Ankylosing Muscular Dystrophy

A pilot trial conducted jointly by Germany and the United States investigated and explored the use of medical cannabis in patients with ankylosing muscular dystrophy. The subjects, aged between 18 and 60 years, were surveyed about their experiences with medical cannabis, covering the route of administration and the perceived effect on symptom relief. The majority of subjects expressed interest in using medical cannabis products or participating in clinical trials.

The survey results showed that many patients reported regular use of medical marijuana or cannabinoids and subjectively perceived improvement in symptoms such as muscle pain, myotonia and muscle stiffness. Notably, reports indicated minimal side effects, highlighting the potential efficacy of medical cannabis in the treatment of ankylosing muscular dystrophy.


Clinical Study of Cannabinoids in the Treatment of Ankylosing Muscular Dystrophy

The Ludwig Maximilian University of Munich conducted a clinical study on six patients suffering from dystrophic and non-dystrophic ankylosing muscular dystrophy to assess the effectiveness of cannabinoids in relieving symptoms. Over a four-week period, the subjects were given THC and CBD oils in varying ratios and doses:

Weeks 1-2: THC: CBD = 1:10; 1.10 mg of THC and 10.29 mg of CBD twice daily.

Weeks 3-4: THC: CBD = 1:6; 3.31 mg THC and 20.58 mg CBD each time, twice daily.

The results of the study showed significant improvement in myasthenia gravis symptoms, especially in the last weeks of treatment. In addition, muscle pain and some gastrointestinal symptoms were relieved in most patients. The only reported side effect was an aggravation of constipation in four of the six subjects.


Conclusion

Chronic pain and muscle spasms are common and debilitating symptoms in patients with muscular atrophy. Cannabinoids, particularly THC, CBD, and CBDV, have demonstrated effectiveness in managing these symptoms and may reduce reliance on traditional pain medications, such as opioids, which carry risks of addiction and other side effects. The muscle-relaxing properties of medical cannabis can also help alleviate muscle spasms, further enhancing the quality of life for individuals with muscular atrophy.

Although preliminary research findings are encouraging, scientific studies on the use of medical cannabis for treating muscular atrophy remain limited. However, there is an increasing body of evidence suggesting that cannabinoids may have significant benefits in symptom management, particularly for chronic pain and muscle dysfunction. Additionally, the role of the endocannabinoid system in muscle development and repair highlights the potential of cannabinoid therapies in improving muscle health and function.

Continued research and clinical trials are essential to fully understand the therapeutic potential of medical cannabis for muscular atrophy and to establish standardized treatment protocols. As interest in this field grows, it is hoped that future research will provide more effective and personalized treatment options for patients with muscular atrophy, improving their quality of life and overall well-being.