CBD and the Treatment of Multiple Sclerosis

Cannabidiol and neurodegenerative diseases

Over the last couple of years, ethnomedicinal research has expanded rapidly, and Cannabis sativa is perhaps the most widely studied plant so far. Before the advent of modern research, cannabis sativa has been used for the management of seizure disorders and movement disorders. Interestingly, only little scientific explanation exists for the therapeutic effects of cannabinoids on the brain and vital sections of the central nervous system. 

After many anecdotal reports on the efficacy of cannabis extracts in managing chronic human diseases, different scientific inquiries have been launched to establish a standard use for cannabis-derived products in humans. Now, there is a scientific basis establishing the role of cannabinoids in cell-to-cell signaling, glucose metabolism, memory formation, and appetite stimulation. Different literature reviews, experiment reports, and trial documents have also emerged on the potential of cannabidiol in the management of neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and Huntington’s diseases, as well as multiple sclerosis. 

Pathophysiology of multiple sclerosis

Multiple sclerosis (MS) is a progressive, chronic neurological diseases of the central nervous system (CNS). Primarily, this disease destroys the myelin sheaths protecting the nerve cells of the brain and spinal cord. Based on disease course, multiple sclerosis is clinically categorized into any of four basic classes: relapsing-remitting MS, secondary progressive MS, primary progressive MS, and progressive-relapsing MS. 

Although MS is considered the most common cause of neurological disability, its etiology is largely unknown. The most widely accepted explanation for the cause of multiple sclerosis implicates the central nervous system’s autoimmune reaction. T-lymphocytes, oligodendrocytes, and macrophages infiltrate the CNS, causing multifocal inflammation is the primary cause of myelin sheath destruction. This destruction results in the formation of CNS plaques composed of inflammatory cells and demyelinated axons in the white and grey matter. The plagues develop into lesions disrupting the normal transmission of nerve impulses leading to neuronal dysfunctions diagnosed in people with multiple sclerosis (PLwMS). 

In 2006, the journal Clinical Microbiology Reviews published a report examining the link between autoimmune diseases and infections. Study reports suggest that exposure to environmental factors, viral and bacterial agents, including human herpes virus, Epstein Barr virus, and mycoplasma, can also contribute to the onset of multiple sclerosis. In the U.S., multiple sclerosis affects approximately 400,000 people, with a common predisposition for young adults. As it stands, there exists no single diagnostic test for the disease. A confirmed diagnosis is based on the presence of at least two different lesions in the white matter, chronic inflammation of the CNS, and the occurrence of associating symptoms in patients. The symptom presentation in people living with multiple sclerosis includes visual disturbances, fatigue, cognitive impairment, movement disorders, sensorimotor defects, and depression.  

Scientific basis for the management of multiple sclerosis with CBD

Conventional therapy for the management of multiple sclerosis generally includes the use of immunomodulation agents, anti-inflammatory agents, and corticosteroids. Basically, these therapeutic agents inhibit the activation of immune cells, decreases myelin degradation, and reduction of inflammation. These agents, however, do not stop the progression of neurodegeneration. 

Endocannabinoids synthesized by the endocannabinoid system have long been known to have significant effects on the immune cells. CB2 receptors are prominently distributed in the immunomodulating cells, prompting researches into the potential benefits of cannabinoids in the management of autoimmune diseases. The Journal of Neurochemistry published a report suggesting that CB2 receptors are increasingly produced on microglial cells as a direct response to an inflammatory stimulus. Other receptors of the endocannabinoid system affecting minor biological actions include PPRAs and transient receptor potential (TRP) channels are other receptors of the endocannabinoid system with important roles in the body’s cellular inflammatory process. 

Summarily, the documented effects of cannabinoids on immune cells, microglia, astrocytes, oligodendrocytes, and the blood-brain opened up scientific inquiries into the possibility of managing PLwMS using cannabidiol as an alternative therapy. The first reported study examining the beneficial effect of cannabinoids in the management of multiple sclerosis was published by the Journal of Clinical Pharmacology in 1981.

Symptom improvement in multiple sclerosis with CBD

In 2013, the journal Neurobiology of Disease published a research report detailing the findings of the effects of cannabidiol in a viral model of multiple sclerosis. With the model, the research team demonstrated that cannabidiol downregulates the expression of vascular cell adhesion molecule and chemokines, reduces the production of pro-inflammatory cytokines, and attenuates the activation of microglia. The highlight of this research is contained in the concluding statement that confirmed the long-lasting therapeutic effects cannabidiol in the improvement of MS symptoms.  

Sativex, a cannabis-based oromucosal spray containing a 1:1 ration of cannabidiol and delta-9-tetrahydrocannabinol, was approved by the FDA as a drug for adjunctive treatment of neuropathic pain in multiple sclerosis. Since its approval, different clinical studies and animal models have been conducted to evaluate the efficacy of the drug and other cannabis-derived products. A double-blind, placebo-controlled, parallel-group study of Sativex was conducted in subjects with symptoms of spasticity due to multiple sclerosis. The 15-week study observed symptoms improvement in a pool pf 337 subjects. As published by the journal Respiratory Physiology and Neurobiology, report analysis suggests that the cannabinoid-derived drug significantly reduces treatment-resistant spasticity in subjects with advanced multiple sclerosis.     

Beyond the improvement of spasticity in MS patients, cannabidiol has also shown a potential therapeutic effect in ameliorating motor symptoms and improving disease prognosis. There are accumulating research studies suggesting that cannabis-derived extracts selectively target CB2 receptors to dampens the immune response of CNS to autoimmune and inflammatory reactions. This has opened up different speculations about the possibility of cannabidiol in halting the neurodegenerative process causing multiple sclerosis. Although this idea seems futuristic, there is research report lending credence to this proposition. 

Fitoterapia published the report of a study aimed at investigating whether purified cannabidiol may counteract the development of multiple experimental sclerosis. Mice subjects were treated daily intraperitoneal dose of CBD after inducing multiple sclerosis using the Experimental Autoimmune Encephalomyelitis model. Data gathered from this research suggests that purified CBD promotes neuronal survival and downregulates the PI3K/Akt/mTOR pathway. Conclusions from this report open up a new line of the therapeutic target for cannabinoids in the treatment of multiple sclerosis. 

REFERENCES

• https://pubmed.ncbi.nlm.nih.gov/16418524/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241505/#!po=31.9767
• https://pubmed.ncbi.nlm.nih.gov/23851307/
• https://pubmed.ncbi.nlm.nih.gov/20307378/
• https://pubmed.ncbi.nlm.nih.gov/27890794/
• https://www.projectcbd.org/hub/ms
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC584292/#!po=51.389
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3151595/#!po=0.641026