By Mark Durrand

Intro and Concepts

This article examines two aspects of the Endocannabinoid System (ECS). The first
centers on the crucial role the ECS plays in managing the gastrointestinal process, with a particular focus on dysregulation leading to Inflammatory Bowel Disease (IBD).

The second area focuses on the role the ECS plays in the experience and management of stress and anxiety, especially the effects of chronic forms of stress such as Post-Traumatic Stress Disorder (PTSD) (1). For both areas, this article considers the potential of Medical Cannabis as a therapeutic treatment complementing the work of the ECS as it guides the body toward homeostasis.

What’s Actually Going On in Your Body

First, let’s gather a sense of some basic terms and concepts that will be useful, and don’t worry, each of these will be expanded upon throughout what follows.

Two Types of Cannabinoids: From Within & From Plants

Cannabinoids are naturally occurring compounds that have significant effects on our bodies and work through what is called the Endocannabinoid System. They are created within our bodies as well as by the Cannabis plant (although a few other natural sources of cannabinoids may exist).

Cannabinoids made inside our bodies are called endocannabinoids (the prefix “endo” here means within and contained by the body), while plant-derived compounds are called phytocannabinoids (the prefix “phyto” indicates its origin within plants).

How Cannabinoids Send Signals

When cannabinoids are present in the body, produced endogenously or consumed in plant form, they serve as ligands. Ligands are molecules or other compounds that contain messages or signals that can be received by microscopic receptors on the surface of cells.

Receptors acquire the message contained within the ligand and pass along those signals to other parts of the body that induce changes within bodily systems with the goal of maintaining overall “balance.”

Why Balance Matters: Introducing Homeostasis

Lastly, and following from the previous, the collective task of our bodies’ complex signaling systems is to maintain what is called homeostasis. Homeostasis refers to the necessary state of internal balance required for our bodies to function properly, and as we will see, the ECS is a significant player in maintaining our bodies’ crucial equilibrium.

Systems and Signaling

How the Body Communicates: Ligands and Receptors

“Ligands” and “receptors” are key elements that allow one part of the body to communicate with other parts of the body. One helpful way of understanding the relationship between ligand and receptor is to think of the receptor as a lock, and a ligand as a key that fits the lock.

Fight or Flight: A Familiar Example

For example, most readers will be familiar with the way our bodies react to stresses associated with perceived danger or threat with what is usually called the “fight or flight” response. When we feel under threat, our adrenal gland releases the hormone adrenaline (technically called “epinephrine”). It serves as a ligand containing instructions that target specific receptors that then tell the body what to do.

In the case of adrenaline, the receptors pass on the ligand’s message to raise our heart rate, increasing blood flow and energy toward our muscles in preparation for action.

More Than Just Hormones: Ligands from Outside the Body

Not all elements that function as ligands are made inside the body; most of the things we eat, drink, or otherwise consume contain compounds that activate receptors. Caffeine in our morning coffee is among the most common examples, it connects with (or binds with, or “unlocks”) a receptor that delivers a message preventing feelings of tiredness and fatigue.

Cannabinoids as Keys: A Special Class of Ligands

Phytocannabinoids are another source of ligands, the most famous of which are THC, which is well-known principally for its intoxicating effects, and CBD, which, although not intoxicating, interacts with receptors in the body in significant ways (more on these later).

The Discovery of the Endocannabinoid System

The felt effects of the phytocannabinoid THC have long been observed and the effects of CBD have long been theorized. Still, the mechanics of just how these two cannabinoids affect the body have only recently begun to be understood (2).

From the late 1980s to the early 1990s, researchers discovered receptors activated by phytocannabinoids; these came to be called Cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors (3). This was a significant discovery, but like all major discoveries, it also raised questions. Notably, and simply put, why do we have these receptors in the first place?

As the famous Cannabis researcher Dr. Raphael Mechoulam and others note, It would have been absurd to assume that these receptors exist in our bodies because a plant just happens to produce compounds that affect them, and so researchers began looking for compounds originating within our bodies (endogenous compounds) that unlock CB1 and CB2 receptors.

Researchers soon discovered two such elements that were created by the body and appeared explicitly designed to target the recently described receptors - these ligands came to be called anandamide and 2AG (4).

Mapping the ECS: Receptors and Ligands

The ECS is vast throughout the body, but it principally consists of CB1 and CB2 receptors and their endogenous ligands, Anandamide and 2AG.

Both kinds of receptors are found throughout the body, but are centralized in distinct areas; CB1 receptors are concentrated throughout the brain and the central nervous system (CNS) and are unlocked mainly by Anandamide (although 2AG has some activity there too); and CB2 receptors are highly prevalent in the immune system which is centered in the gastrointestinal tract – or the “gut” to put it simply – and are activated principally by 2AG (although Anandamide has some activity there too).

Within the central nervous system, CB1 receptors help to modulate signaling between our brains and our bodies, and among other things contribute to the body’s management of pain, anxiety, and fear; CB2 receptors help regulate gut function and immune health among a host of other things. 

The ECS: A Guardian of Balance

What we see with the ECS is a system that overlaps with and interacts with other bodily systems in a fashion that aims to achieve homeostasis across and among our many systems.

In other words, a properly functioning ECS is constantly monitoring the body's internal conditions and maintaining balance even while engaging with external stimuli threatening to destabilize the organism's internal state.

Real-Life Example: Adapting to Environmental Stress

For instance, our bodies require that an internal temperature within a very narrow range be maintained in order to function properly, which means that the chill of winter and the swelter of summer are potentially destabilizing.

In order to maintain the proper temperature as we move from one environment to another, our systems must adjust to the changing temperatures outside the body by respectively raising or lowering our internal temperature to maintain the correct range.

Things like blood pressure, oxygen, and glucose levels likewise must be maintained within a fairly narrow homeostatic range. As the following examples indicate, research shows that the ECS is significantly invested in maintaining balance among bodily systems.

Example 1: The Gut - Inflammatory Bowel Disease (IBD)

Inflammatory Bowel Disease (5) refers to a collection of extremely debilitating conditions that negatively affect the function of the gastrointestinal tract – the most commonly known are Crohn’s Disease and Ulcerative Colitis – and according to the Centers for Disease Control there are potentially in excess of 3 million Americans experiencing this dysregulation, and the number of persons suffering from these conditions is sharply on the rise (and, in the year 2018, the cost of treatment reached well in excess of 8 billion dollars) (6).

The ECS and the Immune System in the Gut

Significantly, the immune system is centered within the gut and contains a very high concentration of CB2 receptors, which led researchers to hypothesize that part of the problem at the root of IBD may relate to the health of the ECS (7).

Following this line of reasoning, researchers tracked the success of treating persons with various forms of IBD with Cannabis. Sufferers of these symptoms given therapeutic doses of THC and CBD showed marked improvement in symptoms and an overall increase in quality of life. The exact mechanisms at work remain to be described, but the success of treatment indicates a clear direction for continued research. Significantly, persons undergoing cannabinoid therapy reported no negative side effects.

Restoring ECS Tone Through Therapy

In terms of discussing the relative health of the ECS, researchers and medical professionals refer to the condition of the ECS as having “tone”, similar to how we might understand the idea of “muscle tone” to refer to the general health and condition of a person’s skeletal muscles.

Likewise, an ECS that is out of balance or otherwise not functioning properly is said to have poor “tone.”

The effectiveness of Medical Cannabis therapy in treating IBD suggests that it may help restore proper “tone” to the ECS and thus contribute to the health of the gut; in so doing it may be partly responsible for restoring health, regularity, and internal stability – not to mention greater confidence and dignity – to persons with chronic gastrointestinal disorders encompassed by IBD.

Example 2: Stress Management

Stress and ECS Imbalance

It is well established that exposure to stress has a significant impact on the status of the ECS. One such effect stress has is to downregulate Anandamide while simultaneously upregulating 2AG. This is referred to as a “bidirectional” response, with one component of the system increasing in effect, and another decreasing. The downregulation of Anandamide and the correlating reduction in CB1 activity appears to bring about higher levels of fear and anxiety (8).

When Fear is Useful

Ironically, this can be a welcomed situation – temporarily.

Recall the significance of the adrenaline response to a perceived threat; danger appears, Adrenaline is released charging the body with the capacity to contend with the threat, and then the jolt of energy and motivation is put to use in fight or flight mode.

Balancing Fear and Recovery

Why can this be good? Because in the face of danger, fear can have a role to play in keeping us safe. The body’s Adrenaline response is one part of a larger – and crucial – bodily system called the HPA Axis which involves the joint operations of the hypothalamus and pituitary glands in addition to the adrenal gland.

There is a great deal going on here that is beyond the scope of this article, but suffice it to say that where the HPA axis functions to raise stress levels, the ECS successively calms the HPA activity once danger has passed bringing balance back to the system.

Point–Counterpoint: Systems in Dialogue

The aim as we’ve noted is homeostasis and interactions between systems involve a kind of “point – counterpoint” action in which one system asserts itself to facilitate change in the body, while another system forms a counter effect so as to prevent a radical change that would be a further threat to the body’s internal equilibrium.

Chronic Stress, ECS Imbalance, and Mental Health

It is now widely recognized that the effects of stress, especially chronic stress, are highly dysregulating to bodily systems, and can result in emotional and mental imbalances, and Medical Cannabis has become a significant avenue of mental health care.

One well-known example is Post-Traumatic Stress Disorder. Treating PTSD with Medical Cannabis shows tremendous promise across an array of symptoms that characterize the disorder, from improved sleep and reduction in nightmares and other intrusive sleep disturbances to an overall sense of well-being and improved quality of life (9).

Cannabinoids as a Therapeutic Bridge

The phytocannabinoids THC and CBD are not equivalent to endocannabinoids, yet their substantial interactions with the ECS pose the question of what therapeutic value Cannabis flower, edibles, and other Cannabis-derived products may have in nurturing our imbalanced systems back to homeostasis.

To my mind, the two instances reviewed deliver at least a partial answer to that question optimistically in the affirmative. 

References

1. Chopra MP, Hongmei Zhang, Kaiser AP, et al. PTSD Is a Chronic, Fluctuating Disorder Affecting the Mental Quality of Life in Older Adults. American Journal of Geriatric Psychiatry. 2014;22(1):86-97. 

2.  Wilson, J. “Cannabinoid Science: Past Present and Future with Jason Wilson, MS: Cannabis Science History” Curious About Cannabis, YouTube. https://www.youtube.com/watch?v=F8tqGCgWEj4.

3. Devane WA, Dysarz FA, Johnson MR, Melvin LS, Howlett AC. Determination and characterization of a cannabinoid receptor in rat brain. Molecular Pharmacology. 1988;34(5):605-613.

4. Mechoulam, R. “Endocannobinoid System: A Fifty year Trip” Medicinal Genomics, YouTube. Endocannabinoid System: A Fifty Year Trip - Raphael Mechoulam

5. IBD Facts and Stats. https://www.cdc.gov/inflammatory-bowel-disease/php/facts-stats/index.html

6. Inflammatory Bowel Disease (IBD) Basics. https://www.cdc.gov/inflammatory-bowel-disease/about/index.html

7. Aloisio Caruso E, De Nunzio V, Tutino V, Notarnicola M. The Endocannabinoid System: Implications in Gastrointestinal Physiology and Pathology. International Journal of Molecular Sciences. 2025;26(3):1306. doi:10.3390/ijms26031306 https://www.mdpi.com/1422-0067/26/3/1306

8. Morena M, Patel S, Bains JS, Hill MN. Neurobiological Interactions Between Stress and the Endocannabinoid System. NEUROPSYCHOPHARMACOLOGY. 2016;41(1):80-102. doi:10.1038/npp.2015.166

9. Steardo L Jr, Carbone EA, Menculini G, Moretti P, Steardo L, Tortorella A. Endocannabinoid System as Therapeutic Target of PTSD: A Systematic Review. LIFE-BASEL. 2021;11(3):214.  https://doi:10.3390/life11030214

About Mark Durrand:

Mark is a gardener, a medical Cannabis patient, and a seasoned educator with over twenty years of experience teaching in higher education..

Contact Mark through the e-mail link below to learn more about his services.

Effective Cannabis Newsletter is a platform to educate on the vital role of the Endocannabinoid System (ECS) in one's health. The information is not intended or implied to be a substitute for professional medical advice, diagnosis, or treatment. All content, including text, graphics, images, and information, contained in or available through this newsletter is for general information purposes only. It is not medical advice; it is health awareness.