Chapter 5: Musculoskeletal Health and Disease


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Human Musculoskeletal System

The musculoskeletal system is composed of two orders, the muscular and skeletal, both of which are necessary for movement and support. The system is composed of both hard tissues such as bones and cartilages and soft tissues like muscles, tendons, synovial membranes, joints capsules, and ligaments.

The skeletal system represents the arrangement of bones, their connections that form joints permitting specific movement. Lubricative cartilage preventing frictional degradation protects the joints.  Muscle fibers and connective tissues that cling to the skeletal frame form the muscular system. The contraction of muscles facilitates movement of the attached bones. Besides movement and support functions the musculoskeletal system protects the vital organs, ensures stability, stores calcium and phosphorus. Even the formation and supply of hematopoietic components happens in the bone marrow.3

The musculoskeletal system like all systems of the body is also affected by the endocannabinoid system. Clinical endocannabinoid deficiency, CECD leads to disorders relating to the pathologic conditions of bones and muscles, ultimately affecting both the function and integrity of the musculoskeletal system. A system which is populated by cannabinoid receptors, which are original targets for disease treatment. 1, 10, 17

CBD and Musculoskeletal Health and Disease

Osteoarthritis, rheumatoid arthritis, osteoporosis, bone cancer, bone fracture and muscle spasm all correlate with a clinical endocannabinoid deficiency (CECD) and reactive oxidative stress. When the body is injured, it triggers an active inflammatory response. This response mitigates the damage through the microglial cell and macrophage release. The activation of microglial cells and macrophage also leads to the release of glutamate, reactive oxidative species (ROS), nitric oxide (NO), and tumor necrosis factor (TNF). These releases escalate inflammation, and progress to microvascular, osteoblast and osteoclast decay as well as endocannabinoid degradation. Studies have suggested that oxidative stress response, activation of microglial cells can be blocked by cannabidiol administration, thereby reducing damages caused by the inflammatory responses.1, 2, 5, 6, 10, 11, 12, 17, 19, 21, 22, 23


There are various forms of arthritis, the most common is osteoarthritis, a musculoskeletal disease that causes an inflammatory response affecting joints, bones, and cartilages. Osteoarthritis can impact every joint in the body, but it commonly strikes the spine, knee, hands, and hips.  The disorder occurs when the protective cartilage in the joints degrades over time. As the bones lose their protective film and contact becomes more direct, the symptoms become more pronounced.

The clinical endocannabinoid deficiency associated with osteoarthritis can be genetic and or acquired. It targets CB2 receptors in the musculoskeletal system. Obesity, sedentary lifestyle, smoking, and traumatic injury are all risk factors for an acquired CECD.

Preventive administration of CBD and post diagnosis of osteoarthritis can both reduce the inflammatory response throughout the musculoskeletal system. Studies have shown that increasing anandamide concentrations would enhance cannabinoid binding to the CB2 receptors limiting the degradation of cartilages.2, 9, 22, 24

Rheumatoid Arthritis

RA, rheumatoid arthritis is a long-term autoimmune disorder that primarily affects the joints in the musculoskeletal system. RA impacts mobility and quality of life, but as it progresses its effects can reach the cardiac, pulmonary and ocular systems and can be related to other autoimmune disorders. Typical symptoms of the disease are warm and swollen joints, commonly localized in the wrists and hands.

People who have rheumatoid arthritis have been found to have irregular CB2 receptors that result in an excessive inflammatory response. Research has concluded that cannabidiol is a suitable candidate to reduce the inflammatory response and enhance CB receptor receptivity. Preventive administration of CBD enhances receptivity binding through lipid neurotransmitters. These effects would help manage symptoms of RA including mobility issues.4, 5, 6, 7, 9, 13, 14, 17, 20, 22-25

Bone Cancer

There are two classes of bone cancer, primary and secondary. Primary bone cancer is a malignant tumor in the cells of the bone, destroying bone tissue. Secondary bone cancers are a subsequent effect from preexisting cancer that is affecting the thyroid, prostate, breast, lungs, ovaries, uterus and kidneys.

Bone cancer is associated with a clinical endocannabinoid deficiency manifesting in an abnormal function in the CB2 receptors. Research confirms the administration of cannabidiol can prevent metastasis from primary cancer sites. 26, 27

Osteoclasts and Osteoblasts

Osteoclasts and osteoblasts regulate bone health and skeletal system homeostasis; both are types of bone cells, each with a different function. Osteoblasts form new bones and mineralize bone structure, while osteoclasts break down bone tissue. Both processes are necessary for maintenance, repair, and restructuring of bones.

The endocannabinoid system balances the immune function in the skeletal system that regulates cellular production. Osteoclast impairment is a CECD, that affects both the stability and strength of the skeletal system. Research concurs that administering CBD will help regulate the functions osteoclasts and osteoblasts by modulating CB2 receptors.23, 25, 28, 29


The overactive or overproduction of osteoclasts can cause the bones to be porous. The bone density and mass would be so little that the skeletal system becomes weak and prone to severe injuries such as breaks and fractures. The microstructural changes associated with osteoporosis result in posture alterations and pain.

Osteoporosis is both an acquired and genetic CECD. The primary affected by this disease are perimenopausal women and the elderly and is common to be related to mortal hip and spinal fractures. Cannabidiol administration is crucial in achieving bone cell homeostasis through CB2 regulation.

Bone Fracture

A traumatic injury to the bone can cause fractures resulting in severe pain, decreased movement, and range of motion. The endocannabinoid system already regulates the overall balance of the skeletal system by influencing the formation of osteoblasts and osteoclast. Regulating CB2 receptor receptivity and increasing anandamide concentrations can lead to pain relief. Cannabidiol administration can help treat the pain and also enhance traumatic recovery.5, 8

Muscle Spasms

Spasms of the skeletal muscles are the contraction of involuntary muscles, which produces a hypertonic response and pain. The force and severity of the muscle spasm depend on the excitatory CB1 receptors. Anandamide levels are depleted in a CECD, causing hyperactivity of misinformed nerve impulses, consequently the loss of mobility and disabling pain. Restoring the function of CB1 receptors with CBD administration would increase anandamide levels and result in analgesia. Increased CB2 functions can also modulate inflammation and irregular immune responses. Cannabidiol can prevent muscle spasm onset and also as a post-incident treatment to reduce symptoms.1, 10, 15, 16, 17, 18, 24


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