Can Anxiety Be Caused By A Deficiency Of The Endocannabinoid

System In The Body?

Stress and anxiety are forces that the body’s natural physiological mechanisms respond to. Everything from danger to increased pressures in a relationship, job requirements or a combative encounter. Stress is a normal adaptation, a healthy response that is manifested when the body is challenged in a way that causes a physiological response from the bodies limbic system to meet the challenge and to keep this within a realm that is considered normal. The adaptation to stress is a vital action-reaction to our environment, without it we could not thrive and in some situation survive.

Research is showing that those individuals that have lost the capacity to adapt and thrive under stress have a verifiable deficiency in the bodies endocannabinoid system.

Difference Between Stress and Anxiety

Stress in a medical or biological context is a physical, mental, or emotional factor that causes bodily or mental tension. Stresses can be external, from the environment, psychological, or social or internal from an illness. Stress is a short-term response to a situation which requires a physiological adaptation from the person involved. The requirement of meeting a deadline can induce stress, which can also serve as motivation. Stress is not always a bad thing when it is in moderation and is not extended over a prolonged period of time.

If left unchecked, stress can lead to a variety of health conditions such as specific phobia’s, Panic Disorder, Social Phobia/Social Anxiety Disorder, PTSD/ Post Traumatic Stress Disorder, GAD/Generalized Anxiety Disorder, Agoraphobia and a multitude of symptoms, palpitations, tachycardia, shortness of breath, musculoskeletal pain, restlessness/sleeping difficulties, lack of ability to focus, sweating or chills at abnormal times. Additional signs are the fear that you’re going to die, having trouble breathing or a feeling as if you’re choking, numbness or tingling sensations in parts of your body, chest pain, lightheaded, dizzy, or a feeling that you might pass out or feeling overheated.

A study published in the Journal of psychosomatic research found that anxiety symptoms were associated with the greater incidence and likeness a person would suffer from difficulties with normal digestion, breathing difficulties, asthma, heart irregularities and abnormalities, head pain, head ache and migraines, vision disturbance, musculoskeletal pain. Research has also suggested that anxiety is associated with an increased risk for heart disease, heart failure, and stroke.

Anxiety is a reaction to stress that typically extends beyond the immediate threat or situation. Anxiety is defined as a state characterized by worry, apprehension, and physical symptoms. Like the tension caused when an individual anticipates danger, catastrophe, or misfortune. The threat the person is responding to may be real or imagined or internal or external. It may be an identifiable situation or vague, even unknown. In any case the body mobilizes itself to meet the threat, whether this is real or imagined: Muscles become tense, breathing becomes faster, and the heart beats more rapidly. Anxiety may be distinguished from real fear both conceptually and physiologically.

Over 40 million U.S. adults are affected by an anxiety-related disorder. Some of these include: Generalized Anxiety Disorder, Obsessive Compulsive Disorder (OCD), Panic Disorder, Post Traumatic Stress Disorder (PTSD), Social Phobia (Social Anxiety Disorder).

What Stress Does to the Brain

Acute stress is short lived and useful. Going into an athletic competition, stress can produce the “fight or flight” response necessary to perform. Cortisol is the hormone released to generate this response. When cortisol levels remain elevated from prolonged stress it has a negative impact on the brains tissue, the stress is considered chronic rather than acute. High levels of chronic stress cause your brain to be unable to learn and to forget things. That’s because chronically elevated cortisol levels erode neurons.

Chronic stress destroys the hippocampus overtime- over-pruning its dendrites, killing its neurons, and preventing neurogenesis.

Prolonged high levels of cortisol can lead to a number of health problems and is not to be taken lightly damaging the hippocampus, limbic cortex and amygdala which has a primary role in the processing of memory, decision-making and emotional responses (including fear, anxiety, and aggression). Prolonged high levels of cortisol also have a negative impact on weight, hormone imbalances, digestion, bone density, heart disease and diabetes. When cortisol continually stimulates the amygdala and overwhelms other body systems for an extended period of time it alters the amygdala, stress actually increases the physical size of the amygdala, its activity level and its number of neural connections. The larger the amygdala gets, the more intense your fear and anxiety becomes. It’s a vicious cycle and wreaks havoc with many other body functions and lays the foundation for anxiety.

The amygdala is part of the brain’s limbic system, it supports emotion, behavior, motivation, long-term memory, all of your emotional life is housed in the limbic system, of which the amygdala is a vital part.

Homeostasis is the body’s adaptation to equalize, adjust and maintain its inherent stability

The endocannabinoid system is one of the biological systems, largely responsible for achieving and maintaining homeostasis in your body. The endocannabinoid system has more cell receptors than any other system in the human body.

Endocannabinoids are cannabinoids that the body naturally produces without outside influence. The two primary endocannabinoids are anandamide (AEA) and 2-Arachidonoylglycerol (2-AG). These molecules are created on demand and interact with receptors to restore balance as needed. These two endocannabinoids under normal circumstance are suppose to protect the brains limbic system and amygdala by modulating the cortisol levels and the damage they can do. If the body is unable to manufacture sufficient endocannabinoids the ground is laid for anxiety and anxiety related disorders.

CB1 and CB2 cannabinoid receptors are located throughout the entire body in varying quantities. The CB1 cannabinoid receptor is a "G coupled protein" expressed largely in the brain.

Communication is Key

One quality that sets cannabinoid receptors apart from other receptors in the body is their ability to conduct retrograde neuron signaling. Typically, one neuron sends a signal to another with information, but no information is returned. Anandamide is a retrograde messenger, which means that it can invoke a two-way communication system. This explains the ability of the endocannabinoid system to promote homeostasis. The increased communication allows cells to react and respond according to signals received in the brain.

Stress, Anxiousness, and Endocannabinoids

The complex actions of the endocannabinoid system occur throughout the immune system, nervous system and virtually all of the body’s organs including everything from the skin to the brain. Because the receptors allow for retrograde communication, the endocannabinoid system is basically a bridge between the mind and body.

When a potential threat is identified by the amygdala, it sends a signal next door to a part of the brain called the hypothalamus. The hypothalamus is told to activate the HPA/hypothalamus pituitary axis, which leads to the release of the stress hormone, cortisol. Anandamide works as a gatekeeper in the amygdala, deciphering whether a signal should be allowed through. This process allows anandamide to help monitor cortisol release. A build-up of cortisol in the amygdala stimulates anxiety. Prolonged cortisol damages the amygdala causing it to hypertrophy and produces more serious and prolonged effects on memory, decision-making and emotional responses (including fear, anxiety, and aggression). Exogenous, (Exo) outside cannabinoids like CBC have shown to modulate cortisol levels reducing the damage to the amygdala and sparing the limbic system and body from the damaging effects of prolonged and repeated high levels of cortisol.

When the brain is overwhelmed by stress, the two-way communication system allows for cells to talk to each other and find a way to quiet the mind and achieve balance or a baseline stress level, in an attempt to mitigate anxiety. Increased stress also has a tendency to create free radicals, which have been linked to anxiety disorders as well as numerous other health concerns.

The 2006 European weight loss drug “Rimonabant” blocked CB1 receptors. The drug was quickly banned due to severe cases of anxiety, depression and even suicide. It was never approved in the U.S.

Cannabinoid Deficit and Research.

There have been a number of studies correlating a lack of endocannabinoid receptors with depression and anxiety as well as other health conditions. The term Clinical Endocannabinoid Deficiency (CECD) refers to that theory. For more information about medical and scientific studies of CECD and the correlation between the endocannabinoid system, stress and anxiety please investigate the links below, or wait for our next article which will explain further, receptor site endocannabinoid receptor deficiency vs endocannabinoid stimulation deficiency.

Cannabinoids that have shown benefits in treating anxiety and anxiety related disorders are Cannabichromene (CBC), Cannabigerolic Acid (CBG-A). CBC, discovered in 1964 by Israeli researcher Dr. Raphael Mechoulam, his thirty-year study also identified the endocannabinoid system, (ECS). He named it “Endo” to reference made within the body and cannabinoid because cannabis was found to stimulate these receptors. The ECS is known to regulate pain, appetite, inflammation, mood and stress response. The two main endocannabinoids are known as anandamide and 2-AG. The two main receptors are CB1 and CB2.

CBC is considered one of the “big six” cannabinoids out of the more than 130 identified. This therapeutic molecule shares its origin, the acidic precursor CBGA, with the two most famous cannabis-derived chemicals, tetrahydrocannabinol (THC) and CBD (cannabidiol). CBC has been shown to be ten times more effective than CBD in treating anxiety and stress. The CBC molecule binds with cellular receptors outside the ECS and in studies has demonstration activation of these receptors.

In a 2011 study conducted by cannabis research pioneer Dr. Ethan Russo entitled “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects” and published in the British Journal of Pharmacology, Russo and his other researchers found that a CBC displayed “pronounced antidepressant and anxiety effects.”

References:

PLoS One. 2014 Mar 12;9(3):e89566. doi: 10.1371/journal.pone.0089566. eCollection 2014. Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system. McPartland JM1, Guy GW2, Di Marzo V3.

Hill, Matthew N, and Francis S Lee. “Endocannabinoids and Stress Resilience: Is Deficiency Sufficient to Promote Vulnerability?.” Biological psychiatry vol. 79,10 (2016): 792-793. doi:10.1016/j.biopsych.2016.03.2099

Mol Aspects Med. 2018 Dec;64:68-78. doi: 10.1016/j.mam.2018.10.001. Epub 2018 Oct 5. Endocannabinoids, exercise, pain, and a path to health with aging. Watkins BA1.

Nutr Res. 2019 Oct;70:32-39. doi: 10.1016/j.nutres.2019.06.003. Epub 2019 Jun 15. Diet, endocannabinoids, and health. Watkins BA1.

Nutrition. 2011 Jun;27(6):624-32. doi: 10.1016/j.nut.2010.11.003. Epub 2011 Apr 6. Endocannabinoid signaling and energy metabolism: a target for dietary intervention. Kim J1, Li Y, Watkins BA.

Postepy Biochem. 2012;58(2):127-34. The endocannabinoid system and its role in regulation of metabolism in peripheral tissues. Rumińska A1, Dobrzyń A.

Cell Metab. 2013 Apr 2;17(4):475-90. doi: 10.1016/j.cmet.2013.03.001. The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders. Silvestri C1, Di Marzo V.

Chronic stress puts your health at risk, MAYO CLINIC, March 19, 2019,

How stress affects your health. American Psychological Association. http://www.apa.org/helpcenter/stress.aspx. Accessed Feb. 12, 2016.

Stress and your health. U.S. Department of Health and Human Services. https://www.womenshealth.gov/mental-health/good-mental-health/stress-and-your-health. Accessed Feb. 12, 2016.

Fight stress with healthy habits infographic. American Heart Association. https://www.heart.org/en/healthy-living/healthy-lifestyle/stress-management/fight-stress-with-healthy-habits-infographic. Accessed March 4, 2019.

Coping with stress. Centers for Disease Control and Prevention. http://www.cdc.gov/Features/CopingWithStress/index.html. Accessed Feb. 12, 2016.Seaward BL.

Essentials of Managing Stress. 4th ed. Burlington, Mass.: Jones & Bartlett Learning; 2017.Seaward BL.

Managing Stress: Principles and Strategies for Health and Well-Being. 9th ed. Burlington, Mass.: Jones & Bartlett Learning; 2018. https://www.mayoclinic.org/healthy-lifestyle/stress-management/in-depth/stress/art-20046037

https://www.ncbi.nlm.nih.gov/pubmed/27324160

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440426/

https://www.ncbi.nlm.nih.gov/pubmed/25510186 Journal of psychosomatic research, anxiety and depressive symptoms and medical illness among adults living with anxiety