Targeting Cannabinoid Receptors in the Management of Hypertonicity & Cerebral Palsy

A recent medical update in regards to the management of hypertonia has been published in the journal Physical Medicine and Rehabilitation Clinics of North America1, highlighting the employment of medical marijuana and its chemical isolates in pursuit of tempering the frequency and severity of this symptom.

An Overview of Hypertonicity

Hypertonia is both a sign and a symptom of several medical conditions. A sign is something that can be seen by an observer, whereas a symptom is something that is felt by the patient. When thinking about hypertonia, in a word, it could be loosely defined as “rigidity.” However, this definition does not quite encapsulate hypertonicity as a whole. As outlined in Pediatrics, a peer-reviewed journal published by the American Academy of Pediatrics, hypertonia is an “…abnormally increased resistance to externally imposed movement about a joint.”2

Hypertonia can be further classified into four different subtypes: Spasticity, Dystonia, Rigidity, or a combination of some or all of these. It is essential to understand the differences between the different types of hypertonia to know how it can be treated. Treatment strategies may undoubtedly vary depending on the type of hypertonia present.

Spasticity manifests as increasing resistance to an external force of movement on a joint or muscle resulting in an increased rate of the stretch of the muscle fibers and varies by directional joint movement.

Dystonia manifests as either involuntary twisting, writhing, repetitive muscle movements, or abnormal posturing of the body due to these muscle contractions. It can also present as a combination of these symptoms/signs.

Rigidity, unlike spasticity, is independent of strength or speed of external or internal force (i.e., velocity) and thereby involves bidirectional resistance.2

Cerebral Palsy and Hypertonicity

Hypertonicity can be found in many debilitating conditions. However, it manifests commonly in those who suffer from Cerebral Palsy. The particular subtypes of hypertonicity that manifest within this condition are the spastic and dystonic types. Pharmacological intervention with medication (“antispasmodics” such as baclofen, dantrolene, and benzodiazepines) and chemodenveration have been most commonly used to treat symptoms of hypertonicity within cerebral palsy (CP) patients. Chemodenervation refers to the use of a particular type of toxin, botulinum toxin (think of botox), to reduce spasticity and dystonia in CP patients.

An Overview of Cerebral Palsy

CP is a disorder that affects muscle tone, movement, and posture. It results from damage to the brain either in utero (during fetal development) or after birth up to 3 years of age.

CP can only be diagnosed during the late stages of infancy when failure to reach certain developmental milestones (ex. being able to sit unassisted, pulling to stand up straight) raises concern for the potential presence of this condition.

CP is classified into two subtypes: spastic and non-spastic. This is about the type of physical manifestations that may occur. In non-spastic CP, dystonia will be present. In spastic CP, spasticity is prevalent in at least one limb, if not more.

There is currently no cure for CP, which means that the main focus, now, in treating this disease is primarily focused on proper and effective management in improving patient quality of life.

The Use of Medical Marijuana in CP management

The use of cannabinoids in the comprehensive management of CP has become more prevalent within the past few years, with demonstrable efficacy in improvement in patient quality of life. To understand why, we must first understand both how CP and chemical isolates of medical marijuana affect the brain, and how the latter works to buffer the adverse effects of the former.

Understanding the Brain, Cannabinoids, and CP

Cannabinoids refer to the pharmacologically active compounds of marijuana that exert an effect within the human body. Two of the pharmacologically active chemical compounds that have been isolated are THC (9- tetrahydrocannabinol) and CBD (cannabidiol).

CB-1 & CB-2 are cannabinoid receptors that are found within the brain and spinal cord. To understand the effect of cannabinoids on patients with CP, we must realize specifically where these receptors are located, and the significance of those locations.

CB-1 receptors are located in the: hippocampus, basal ganglia, cerebellum, dorsal root ganglia of the spinal cord, and in the peripheral nervous system (in particular the presynaptic sympathetic nerve endings within this system).

CB-2 receptors are located within the periaqueductal gray matter of the brain.

Understanding the manifestations of CP, including hypertonicity, becomes intuitive if we know how some of these locations within the brain and spinal cord can be directly linked to this condition:

Human brain lobes, beautiful colorful illustration detailed anatomy. Sagittal view of the brain. Isolated on a white background.

  • Basal ganglia: responsible for the initiation of movement, motor function, and control of skeletal muscles.
  • Cerebellum: responsible for balance
  • Dorsal root ganglia: carry sensory information to the spinal cord (and has been targeted in CP hypertonicity/ spasticity therapy)
  • Peripheral nervous system: sends signals to muscles through their innervation
  • Periaqueductal grey matter: area in the brain which can provoke reactionary responses that would, in turn, stimulate muscles and their movement.

Given this information, it should come as no surprise that CP will affect some, if not all, of the aforementioned areas of the brain and the spine. It is also, therefore, pertinent to note the relationship between the targeting of these cannabinoid receptors in patients with CP, and the subsequent improvement in their condition as a result.

Limitations of Cannabinoid Receptor Targeting in CP management

The use of cannabinoids in the treatment of spasticity and dystonia is a relatively recent occurrence. Although improvements in patient quality of life have been noted. As a result, a significant lack of data still exists simply due to the latest employment of this particular therapy.

Also, there is currently a lack of evidence that would suggest justification of cannabinoid use in children with CP-related spasticity and dystonia.

Final Thoughts

There has been a sufficient amount of patient data collected that suggests that the targeting of cannabinoid receptors can certainly have the potential to prove itself as a reputable form of therapy amongst the litany of treatments currently employed regularly for CP. In particular regards to spasticity, cannabinoid receptors are not only targeted in the case of CP. They have also been proven to be beneficial in the cases of other diseases, such as multiple sclerosis and epilepsy. Although further research is certainly needed, it appears as if cannabinoids will prove themselves to be a strong contender in the management of hypertonicity.

Bibliography:

  1. Dy, Rochelle, and Desiree Roge. “Medical Updates in Management of Hypertonia.” Physical Medicine and Rehabilitation Clinics of North America, vol. 31, no. 1, 1 Feb. 2020, pp. 57–68., doi:10.1016/j.pmr.2019.09.010.
  2. Sanger T.D., Delgado M.R., Gaebler-Spira D., et al.: Task Force on Childhood Motor Disorders. Classification and definition of disorders causing hypertonia in childhood. Pediatrics 2003; 111: pp. e89-e97

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