Abstract
Amyotrophic lateral sclerosis (ALS) is a degenerative disease that manifests in older adults as a result of death of motor neurons. Incidence is 60-80% sporadic and 10-20% familial. The most common mutations are SOD-1, TARDBP, and FUS. Abnormal protein aggregation, inflammation, and dysfunction of RNA are seen. Tremors, dyslexia, and inability to walk progress to death. No cure is available to date. Medical cannabis may delay ALS progression by its neuroprotective, antioxidant, and anti-inflammatory properties. This chapter examines the effects of cannabinoids in ALS and discusses their mechanisms of action. Several psychoactive compounds like THC delay the progression and increase survival rates in a few animal models including the G93A mouse model. The binding of THC to CB receptors, CB1 and CB2, can reduce glutamate secretion thereby reducing excitotoxicity. Targetting CB1 and CB2 receptors with THC agonists could inhibit inflammatory responses, prevent oxidative damage, and reduce microglial activation. This study reviews the evidence for therapeutic effects of cannabinoids in ALS.
TopIntroduction
Amyotrophic refers to a disease in the lower motor neurons that causes muscle twitch and thinning, of muscle leading to weakness in the muscle. Lateral sclerosis denotes the stiff feeling in the spinal cord's lateral part due to glial cell damage and cell damage in the corticospinal area (Wijesekera & Nigel Leigh, 2009; Oskarsson et al., 2018). On a microscopic basis, axons and neurons are lost in the lateral and anterior parts of the spinal cord (Saberi et al., 2015; Owens, 2017). It is the third most common degenerative disorder (Hulisz, 2018; Gentile et al., 2021). ALS is a neural disorder due to the degeneration of the motor neurons in the lower and upper regions, followed by damage to glial cells. Typical areas of cell damage are in the spinal cord, brain stem, and motor cortex. The reason behind their progression was not known for decades (Hardiman, Al-Chalabi, Chio, et al., 2017; Rowland & Shneider, 2001). Researchers have come up with many speculations regarding neuropathological conditions, but they are still unclear.
In 1824, Charles Bells reported the first case of ALS, and there were many debates regarding this throughout the era. The clinical reason behind the muscle twitch, weakness, lateral sclerosis, and loss of horn cells was reported by Charcot in 1860. Patients associated with ALS start losing their voluntary movements and feel weak and unable to speak and walk; these symptoms worsen in the future stage. Limbic and bulbar onset are common symptoms in patients in the earlier stage. ALS is a progressive disease; the survival range after the symptoms is 3-5 years to the maximum (Kiernan et al., 2011; Kaur et al., 2016). Sporadic cases were 5.2 per 100000 in western countries while 1.5-2.7 per 100000 in Europe and America (Wijesekera & Nigel Leigh, 2009).
Key Terms in this Chapter
Degenerative Disease: Any disease which can worsen in the later stage of progression.
CB Receptor: Cannabinoid receptors are a part of the endocannabinoid system, it is found all over the body.
Atrophy: Reduction in the size of the body part, organ, or tissue-like thinning in muscle.
Progenitor Cells: Cells that have the ability to differentiate into specific cell types.
G-Protein Receptor: These are integral proteins found in eukaryotes that are used to convert extracellular signals to intracellular.
Alzheimer: Neurodegenerative disease causing loss of neurons that eventually results in cognitive impairment and dementia with motor-related problems.
Familial: Any disease that has a record of family history.
Parkinson’s Disease: Age-related progressive neurodegenerative disease characterized by tremor, muscular rigidity, and slow, imprecise movement caused by loss of dopaminergic neurons in midbrain.
Dysphagia: A condition due to loss of neural control in swallowing. It is one of the symptoms of ALS.
Biopsy: A surgical procedure to test the sample by removing a piece of cells or tissue.
Sporadic: Occurring at irregular intervals in time and in people who do not have a family history of a given disease.
Antioxidant: Compounds that prevent oxidation that prevents free radicals from damaging the cells.
Cannabinoid: Compounds found in the Cannabis sativa plant that can interact with the receptors in the brain.
Amyotrophic Lateral Sclerosis (ALS): A neurodegenerative disease caused in humans due to dysfunction of motor neurons.