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Stress and the Endocannabinoid System

Stress is a part of life, but it is important that it does not overwhelm us and do harm. One of the body’s primary counters to the negative effects of stress is the endocannabinoid system or ECS. This critical system is named after the cannabis plant that led to its discovery, but the ECS is influenced by factors well beyond those produced by cannabis. In our body and brain, the ECS serves as a master conductor, sending chemical messages and triggering biological actions that are critical to fighting stress and promoting balance, health, and wellbeing.

How the ECS Functions to Reduce the Effects of Stress

The ECS major role is to promote homeostasis, that internal drive within every cell and our entire system to maintain balance and promote health within its internal environment, even when faced with external changes.

The ECS is known presently to include:

  • Receptor sites on cells, particularly nerve and immune cells, called CB1 and CB2.
  • Compounds known as endocannabinoids produced in the body from dietary fats like anandamide that bind to cannabinoid receptors on cell surfaces.
  • Enzymes that impact the manufacture and metabolism of the endocannabinoid.
  • Associated compounds that support the mechanisms that the ECS activates.

ECS receptors on cell surfaces are similar to locks on a door. When the right “key” in the form of a chemical molecule or agonist binds to the cellular receptor it relays a specific message to the cell that creates a cascading effect in biochemical processes to produce its effect. Most hormones work in this manner. For example, when insulin binds to its receptor on a cell it causes that cell to ultimately allow blood sugar (glucose) to enter the cell.

There are two primary cell cannabinoid receptors CB1 and CB2. These receptors are found throughout the body. However, certain areas concentrate one or the other receptors. For example, CB1 receptors are abundant in the brain while CB2 receptors are more often found on immune cells, in the gastrointestinal tract, and in the peripheral nervous system. The widespread distribution of cannabinoid receptors shows just how important the ECS is to overall bodily function and health.

The natural compounds produced by the body that activate or act like keys on the ECS are referred to as “endocannabinoids.” These compounds are derived primarily from dietary fats with different families of fats (e.g., saturated, mono-unsaturated, omega-6, omega-3, etc.) producing slightly different effects on the ECS. When endocannabinoids physically dock to CB1 or CB2 receptors as well as through parallel measures that do not involve direct triggers an intricate cascade of chemical messengers that send vital information to cells, organs and the nervous system critical to maintaining optimal health and homeostasis.  Activation of CB1 and CB2 receptors changes cellular function, including gene expression and electrical excitability of cell membranes. It is a very powerful event that is critical to the proper functioning of the cell.


Stress is known to produce a reduction in the level of circulating endocannabinoids to result in a deficiency of endocannabinoid activity. The deficiency can range in activity to mild to quite severe. Mild deficiency may produce feelings of being stressed out, anxious, irritability, and fatigue, while more severe deficiency is associated with debilitating ailments such as fibromyalgia, migraine, multiple sclerosis, seizure disorders, chronic fatigue, IBS and more.


Exposure to continued or severe stress is the key factor in developing clinical endocannabinoid deficiency syndrome, but factors such as a poor diet, lack of exercise, drug abuse, environmental toxins, genetics can also be important contributing factors. The deficient function of the ECS is most often associated with a reduced ability or inability to adapt to chronic stress. Prolonged or severe exposure to stress depletes the tone of the ECS, and this, in turn, has an adverse impact on a plethora of physiological processes. And sometimes it is a chicken and the egg scenario whereby deficiency of ECS function or components is responsible for amplifying the negative effects of stress leading to a further deterioration of the ECS.


How to Nourish and Support Endocannabinoid System

While much of the focus on supporting the ECS has been on cannabis compounds, there is a key point that must be realized. The ECS exists and functions independently of cannabis. A more rational approach to enhancing the ECS involves are more comprehensive strategy. For example, critical to the proper functioning of the ECS is having a diet rich in the right type of fats. In particular, the monounsaturated fats (particularly olive oil) and the long-chain omega-3 fatty acids EPA and DHA from fish increase brain and body levels of endocannabinoids as well as sensitize and enhance endocannabinoid receptor binding.


Supporting the ECS is possible by non-cannabis plant extracts that exert novel effects impacting the ECS on multiple levels as well as reducing stress. Specifically, the PhytoCann Complex is a remarkable collection of plant components developed through a collaboration of myself, Giovanni Appendino, Ph.D., and Gaetano Morello, N.D., that nourishes and supports the ECS via five key mechanisms:

  • Helps support the internal production of endocannabinoid.
  • Supports the creation of more CB1 and CB2 receptor sites.
  • Activates directly or facilitates indirectly the binding of endocannabinoids to CB1 and CB2 receptor sites.
  • Protects and preserves ECS function by acting on enzymes that regulate the formation, breakdown, or action of endocannabinoid.
  • Work in parallel manners to reduce stress and/or promote homeostasis.

So, what exactly is the PhytoCann Complex? It is a patent-pending combination of proprietary extracts of Echinacea purpurea, magnolia, zanthoxylum, ginger, peony, and clove oil. These extracts are extremely rich in pharmacological activity beyond the ECS, but what researchers are excited about is how these additional beneficial actions are supported by the ECS and vice versa.



  • Clove oil (concentrated for β‐caryophyllene) – the pain-relieving aspects of clove oil have been well-utilized over-the-years by mothers soothing the irritated gums of teething infants. Clove oil contains several analgesic ingredients, but the one most researched for its effects on the ECS is β‐ This compound is also found in many other herbs and spices. It is able to bind with great affinity to CB2 receptors and that is thought to be one of its primary mechanisms in its ability to reduce pain in its topical application.

  • Echinacea purpurea – contains alkylamides that bind to ECS receptors with great affinity and also prolong the effects of endocannabinoids such as anandamide – which is often referred to as the “bliss” molecule for its anti-stress and mood-elevating effects. Clinical studies with an alkylamide-rich extract of Echinacea purpurea have shown positive effects in promoting feelings of inner peace and reducing the effects of stress.

  • Magnolia – contains magnolol, which is a very potent CB1 and CB2 receptor agonist. What this means is that it is able to bind to both types of CB receptors. Magnolia extracts exert significant effects in promoting a relaxed mental state useful in reducing the effects of stress.

  • Zanthoxylum or Sichuan pepper – contains alkylamides similar to echinacea that display a very strong affinity to CB1 and CB2. These compounds also influence mechanisms involved in the electrical control of cells and work closely with the ECS. The two systems overlap and are intricately interwoven in helping cells communicate with one another.

  • Peony – contains paeoniflorin, which exerts a number of benefits in close harmony with the ECS.

  • Ginger – exerts of a multitude of health benefits some of which are mediated by the ECS. Ginger’s volatile components also influence some of the same channels as zanthoxylum in supporting homeostasis.

One of the great enemies to the integrity and function of the ECS is stress. So, anything that supports our ability to deal with stress enhances the function of the ECS. And likewise, the use of any of the Emerald formulas are in turn, helpful in supporting the ability to deal with stress because of the PhytoCann Complex. EndoCalm and EndoSleep are two specific formulas that contain additional ingredients that are particularly helpful when there is an increased need for daytime and nighttime support. The two formulas can be used in combination when needed.

STRESS = Endo Calm helps relieve occasional stress and anxiety

SLEEP = Endo Sleep supports restful and rejuvenating sleep

MOOD = Endo Bliss helps promote a positive outlook

STAY HEALTHY!
Michael T. Murray, N.D.