Oxidative Stress and Inflammation: How do cannabinoids help?

Introduction

Stress affects everyone regardless of age. Studies report that all generations say they experience stress levels higher than they believe.

Moreover, the pandemic has further evoked stress and frustration caused by unprecedented lifestyle changes, shock, and confusion.

Did you know that WHO has designated stress as the health epidemic of the 21st century?

Hence, it is evident that stress affects overall health by generating free radicals. When these free radicals overwhelm the body, it causes metabolic disturbances, leading to oxidative stress, inflammation, and many diseases. As a matter of fact, the study of free radicals has become indispensable in understanding disease mechanisms.

Therefore, from reading this blog, you will learn,

(a) What causes oxidative stress, how does it affect our health?

(b) How do the therapeutic properties of the cannabis sativa compounds (THC, CBD) prevent inflammatory stimuli, oxidative stress, and inflammation?  

What is oxidative stress?

According to a recent study,¹ Oxidative stress is the imbalance between the production of reactive oxygen species (ROS) and the antioxidant defenses.

A balance between free radicals and antioxidants is necessary for the effective functioning of the various physiological functions of the body, such as metabolism, responsiveness, movements, reproduction, etc. When there is a disturbance in this balance, the body loses its ability to regulate the excess free radicals, a condition known as oxidative stress arises.

What are free radicals?

A study from 2010² defines free radical as an unstable, highly reactive molecular species that can exist independently and behave as oxidants or reductants. 

What is reactive oxygen species (ROS)?

We are aware that oxygen is the most fundamental element for sustaining life. At the same time, it could also cause destructive effects on the human body due to chemical reactions known as reactive oxygen species or ROS. 

Additionally, from the 2015 study,³ we can infer that the toxicity in oxygen is due to the formation of free radicals in the living system, and stress is one of the contributing factors. Moreover, the root cause of many chronic diseases is oxidative stress-induced free radicals and the resultant oxidative injury.

“Basically, I think of free radicals as waste products from various chemical reactions in the cell that when built up, harm the cells of the body.” 

-Dr. Lauri Wright, Dietitian & Assistant professor of Nutrition,  University of South Florida,USA

Discussion

Understanding free radicals are of paramount importance. It leads to realizing the inter-relationship between oxidative stress, inflammation, and several chronic ailments. 

Here is a simplified example to understand free radicals. 

Let us recall some basic chemistry concepts. Cells are made up of molecules, molecules are made up of atoms ( the fundamental unit of matter) and atoms are made of protons, neutrons, and electrons. 

Now, consider an example. 

Let’s say one molecule loses an electron (due to an external or internal factor), it becomes unstable and detaches itself, and becomes a free radical. It begins to seek or steal an electron from another molecule to stabilize itself. This process multiplies and results in a chain reaction leading to oxidative stress or injury. 

Three outcomes occur in the oxidation process. Transfer of atoms, chemical change, and electron transfer from one unit to another.

How are free radicals formed?

Free radicals could be formed endogenously from within the body and due to external factors. They can be grouped in a table as follows:

Endogenous factors	Exogenous factors
Metabolic processes	Exposure to X-rays, ultraviolet rays
Enzymatic and non/enzymatic reactions	Environmental pollution – Air, water, Industrial chemicals, nitrogen oxides,
Chemical reactions	Cigarette smoking, alcohol consumption, wrong food habits.
Side effects from medication, opioids	Severe physical work, exercise, exhaustion, prolonged working hours,  workload, fatigue, sleep deprivation
Anoxia or reduced oxygen supply	Stress, psychological trauma, anxiety, and depression.

How do oxidative stress and inflammation affect our health?

According to the 2015 study⁴ stress-induced oxidative stress and inflammation play a dominant role in aging and development of various diseases. Oxidative stress and inflammation are one of the primary causes that lead to most human diseases. 

They include coronary heart disease, cardiovascular diseases, hypertension, metabolic disorders, diabetes, inflammatory bowel disease, cancer, kidney dysfunction, neurodegenerative diseases, Alzheimer’s and Parkinson’s, Multiple Sclerosis, and many more.

Does CBD help prevent oxidative stress?

We are aware that CBD is a compound of the cannabis sativa plant. Its chemical formula is:

C21H30O2

Twenty-one atoms of carbon, 30 atoms of hydrogen, and two oxygen atoms. How does this simple combination transform into a therapeutic strategy for reducing the impact of inflammation on oxidative stress? 

Let us explore.

The 2011 study⁵ reports the antioxidant properties of CBD that prevent cell death in cultured human and mouse cells. The therapeutic antioxidant properties of CBD and modulation of cell signaling events form the basis of inflammation and oxidative stress.

The study also points out the growing evidence on the role of pro-inflammatory proteins (cytokines), free radical species, and oxidants in causing depression. At the same time, it results in oxidative stress and neuron damage in the brain. In this connection, the antidepressant actions of CBD are highlighted.

Biological activity of CBD

A 2019 study⁶ mentions that conditions such as cardiovascular, neurodegenerative, cancer, and metabolic diseases are usually accompanied by oxidative stress and inflammation. And that the therapeutic potential of CBD for these conditions has been evaluated by several studies. 

Two observations from a 2002 study⁷ could be helpful at this point. 

• Oxidation-reduction (redox) is a regulator of various metabolic functions of the cell. When there is a disturbance ( external or internal) to the redox status, it triggers different responses, resulting in alteration of cell function. 

• Glutathione and thioredoxin are the two major oxygen-reducing systems that maintain redox balance. Oxidative stress profoundly affects both these redox components directly and indirectly. Therefore redox is the two reciprocal processes of oxidation and reduction called a redox reaction. 

Similarly, the 2015 study⁴ also points out that oxidative stress may arise due to deficiency in antioxidant compounds including glutathione. Even highly reactive oxygen species (ROS) could cause glutathione depletion, lipid peroxidation, membrane damage, DNA strand breaks, and protein denaturation. 

In essence, the 2019 study⁶ points out that the development and treatment of diseases are associated with redox imbalance and inflammation. 

• The analysis of CBD’s direct antioxidant activity shows that it can regulate the state of redox balance by modifying the level and activity of oxidants and antioxidants. 
• CBD interrupts free radical chain reactions by capturing and reconstructing them into less active forms.
• CBD reduces oxidative conditions by preventing the formation of superoxide radicals and reduced reactive oxygen species (ROS) production. 
• By lowering the ROS levels, CBD also protects non-enzymatic antioxidants and prevents their oxidation. 
• Repeated doses of CBD in inflammatory conditions increase the activity of glutathione peroxidase and reductase.
• CBD modulates the function of the immune system and suppresses the proliferation, maturation and migration of immune cells. Most importantly CBD reduces the force and effect of inflammatory cell migration.

Do terpenoids help in reducing inflammation?

A 2018 study⁸ reports that different cannabis chemotypes possess distinct terpenoid composition. And these display anti-inflammatory and antinociceptive activities. Terpenoids may reduce the acute inflammation effect, but only cannabinoids have the potential to prevent chronic inflammation symptoms. Moreover, it adds that terpenoids are not as effective as CBD. 

Role of CBD in lessening the effect of inflammation, oxidative stress, cardiovascular disease and health

Hemppedia has compiled several blog posts about the various therapeutic properties of CBD and its applicability in several health conditions. Most importantly, the main biological effects of CBD and its synthetic derivatives centers around its antioxidant and anti-inflammatory properties.   

Moreover, chronic inflammation cannot be viewed as a disease, but a biological process with its prominent role in several diseases like diabetes and cardiovascular diseases, reports a 2016 study⁹

• A 2011 study¹⁰ points out CBD’s antioxidant properties and anti-inflammatory actions on immune cells. It adds that inflammation and oxidative stress are involved in many human diseases by affecting tissue and organ damage and feed off each other. 

• The 2019 study¹¹ reports that CBD acts as an antagonist with steroids, overriding the anti-inflammatory potential of steroids when used in combination. 

• Similarly, a recent study¹² also adds that the hypotensive actions of CBD are often revealed under stress conditions and CBD helps to decrease organ damage and dysfunction, oxidative and nitrative stress, and inflammatory processes. Concerning the use of CBD for cardiovascular diseases, there is further need for clinical research.  

Key Takeaways

• Stress affects everybody regardless of age. It is important to give equal importance to physical and mental health to prevent yourself from stress. 
• Stress affects overall health by generating free radicals. When these free radicals overwhelm the body, it causes metabolic disturbances, leading to oxidative stress, inflammation, and many diseases. 
• A balance between free radicals and antioxidants is necessary for the effective functioning of the various physiological functions of the body.
• The analysis of CBD’s direct antioxidant activity shows that it can regulate the state of redox balance by modifying the level and activity of oxidants and antioxidants. 
• CBD helps to decrease organ damage and dysfunction, oxidative and nitrative stress, and inflammatory processes. 
• Several studies describe CBD as a multi-target molecule, as it acts as an adaptogen and a modulator in different ways by interacting with CB1 and CB2 receptors. 

References

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