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Defining the Endocannabinoid System

The endocannabinoid system (ECS) is a complex network of receptors, signaling molecules, and metabolic enzymes that most people do not know about. A building body of research shows that the ECS has a significant influence on human health and well-being, serving an essential function in the human body: restoring homeostasis via physiological and regulatory mechanisms. The ECS is made up of cannabinoid receptors, endocannabinoids, and metabolic enzymes.


From the discovery of the first phytocannabinoid, the endocannabinoid system has been of great interest to the scientific community for its nearly ubiquitous presence in the human body and its role in key physiological processes. This page serves as the hub for all information relating to hemp and the endocannabinoid system currently present in peer-reviewed scientific literature.

Structure of the Endocannabinoid System

What are endocannabinoids?

There are different types of cannabinoids. One type, called endocannabinoids, is produced on demand in the human body in response to elevated intracellular calcium levels in neurons. 

Two of the most-studied endocannabinoids include:

  • N-archidonylethanolamide (anandamide, AEA)
  • sn-z-archidonoylglycerol (2-AG).

What are cannabinoid receptors?

Cannabinoid receptors are the primary targets of the ECS, bound by lipid signaling molecules called cannabinoids. There are two main types of cannabinoid receptors, which vary in their chemical structure and thus perform different functions in terms of diet, lifestyle, and nutrition:

Cannabinoid Receptor 1 (CB1) is associated with various effects:

  • Psychoactive
  • Neuromodulatory
  • Analgesic

These effects are due to CB1’s activation by tetrahydrocannabinol (THC). Cannabinoid receptors in the brain are mostly expressed as CB1. CB1 is also found in adipocytes (fat cells), hepatocytes (liver cells), and musculoskeletal tissues.

Cannabinoid Receptor 2 (CB2) is associated with anti-inflammatory and immunomodulatory effects but no psychoactive effects. CB2 is expressed in body cells controlling immune function and (potentially) the central nervous system (CNS). Research suggests that secondary metabolites from phytonutrients in plant-based foods enhance the activity of CB2 receptors and confer healthy inflammatory responses.

Read more about endocannabinoid receptors:

Cannabinoid Receptors: CB1 and CB2

Cannabinoid receptors are the primary targets of the endocannabinoid system, bound by lipid signaling molecules called endocannabinoids.

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Endocannabinoid System Activation

Everything you need to know about hemp, the endocannabinoid system, and omega-3 fatty acids

What are the major components of the endocannabinoid system (ECS)? How do omega-3 fatty acids and the ECS act synergistically? What are they key functions of the ECS in the human body? This helpful infographic provides a quick “ECS 101,” useful for a variety of educational situations. Download and print out your free copy today.

View PDF

Role of the Endocannabinoid System

Endocannabinoid system receptors and cannabinoids are present and vital in nearly every area of the human body. Thus, disruption of the ECS has a serious, negative impact on human health. 

The ECS is responsible for basic homeostatic roles:

  • Relaxation
  • Metabolism
  • Sleep
  • Memory

The ECS is also responsible for more complex functions:

  • Neuroplasticity
  • Modulation of embryonic development
  • Neuroprotection
  • Immunity and inflammation
  • Apoptosis
  • Carcinogenesis
  • Pain and emotional memory

What is endocannabinoid tone?

The “endocannabinoid tone” describes as state of proper functioning of the ECS, which depends on the density, functional status, and availability of endocannabinoids. Endocannabinoid tone is influenced by multiple external factors, such as physical activity, eating a well-balanced diet of macronutrients, micronutrients, and phytonutrients, and stress modification. Whatever the reason, endocannabinoid deficiency prevents the ECS from properly regulating homeostasis in the body, but supplementation with phytocannabinoids can resolve some of these issues.

Learn more about how phytocannabinoids supplementation and nutrition interact in this article.

Nutrients Supporting the Endocannabinoid System

Hemp is rich with essential nutrients and bioactive phytochemical metabolites that nurture the endocannabinoid system.

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Hemp, CBD, Marijuana, and the Endocannabinoid System

CBD & the Endocannabinoid System

Cannabidiol (CBD) is a type of phytocannabinoid. Scientists have identified as many as 90 phytocannabinoids.

Hemp & the Endocannabinoid system

Hemp is rich with essential nutrients and bioactive phytochemical metabolites that nurture the endocannabinoid system (ECS). The term “hemp” describes the fiber, stalk, and seeds taken from the Cannabis sativa L. plant species, and hemp has long been applied to food, fiber, and medicine production ever since it originated from Central Asia. The phytocannabinoids found in hemp largely activate cannabinoid receptor 2 (CB2), thus exerting positive, non-psychoactive effects on the human body.

Hemp and Marijuana: Differences

Marijuana is defined in these laws as all parts of the cannabis plant – with the relevant exception being the stalk and seeds (a.k.a. hemp), provided they contains less than 0.3% THC. While state laws are rapidly evolving in the direction of legal marijuana, federal law and many state laws still say marijuana is illegal. A product derived from hemp (stalk and seeds) is not marijuana.

Hemp Oil and CBD Oil: Differences

CBD oil products are being marketed in many places throughout the United States. Like hemp oil, CBD oil is also derived from the stalk and seeds of the cannabis plant, and it is typically formulated and standardized to deliver a stated amount of the phytocannabinoid cannabidiol (CBD).

Purchasing Hemp Oil and CBD Oil

Is it legal to purchase Hemp Oil and CBD Oil?

Many states have passed laws permitting the sale and use of CBD oil – but only in specific circumstances. In these states, the sale and use of CBD oil is often (1) restricted to certain medical conditions and (2) requires the supervision of specific medical practitioners. FDA law and regulation describes that CBD oil currently cannot be sold as a dietary supplement. Unlike CBD oil, hemp oil is legal to sell as a dietary supplement in the United States as long as the hemp material is purchased outside of the United States.

Read more about the legality of hemp:

Legal Status of Hemp

State laws are continuously evolving regarding the legalization of marijuana, however hemp, marijuana, hemp oil, and CBD oil all have different legal...

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How do you know if your Hemp Oil Product will work?

There is more to an effective hemp oil product than just the amounts of phytocannabinoids present. Hemp also contains beneficial amounts of bioactive phytochemical metabolites and essential polyunsaturated fatty acids (PUFAs). 

PUFAs are precursors and homeostatic regulators of endocannabinoids, lipid signaling molecules of the ECS that bind cannabinoid receptors like CB2. Thus, PUFAs represent a key step in maintaining the health of the ECS. Studies have shown that dietary supplementation with fish and/or fish oil containing DHA and EPA promotes specific modulation of the CB2 receptor.

Polyunsaturated omega-3 fatty acids support healthy inflammation. Unhealthy inflammation is a common underlying cause for all systemic imbalances in the body, including in the ECS:

  • Unhealthy inflammation can be induced by tissue stress and systemic malfunction
  • Chronic inflammation can be triggered by disrupted homeostasis
  • Inflammation is also associated with the negative effects of oxidative stress

Endocannabinoid System FAQs

People often ask...

Yes, the human body produces endocannabinoids; they are endogenous. There are also two other types of external (exogenous) cannabinoids that can bind cannabinoid receptors: 

  • Phytocannabinoids (found in plants; i.e. CBD and THC)
  • Synthetic cannabinoids (designed specifically to interact with the ECS)

Learn more about phytocannabinoids and the role the play as part of the endocannabinoid system.

Polyphenols and Glucose Management

Polyphenols are phytonutrients with beneficial anti-inflammatory, antioxidant, chemopreventative, and neuropreventative activity, as well as...

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In order to main systemic homeostasis within the body, lipid signaling mediators called endocannabinoids are produced and circulated to produce certain physiological functions, depending on the physiological need, upon binding to specific cellular receptors (cannabinoid receptors) . This process is governed by the endocannabinoid system (ECS).

Endocannabinoid ligand-receptor mediated cell signaling works similarly to how immune cells and immune receptors function as part of the immune system, and how neurotransmitters work with neurons to transmit chemical messages as part of the nervous system. However, physiological manifestations due to metabolic stress compromise the body’s natural ability to synthesize enough endocannabinoids to feed the ECS effectively. Phytocannabinoids from plants exist in nature and, just like endocannabinoids, are able to bind cannabinoid receptors and regulate physiological functions and endocannabinoid tone in the human body.

Cannabidiol (CBD) is a type of phytocannabinoid found in cannabis products like hemp. Scientists have identified as many as 90 phytocannabinoids.

Hemp, which is made up of the stalk and seeds of the cannabis plant, must contain less than 0.3% THC to be considered a legal product.

Read more about the legality of hemp oil here.

Polyphenols and Glucose Management

Polyphenols are phytonutrients with beneficial anti-inflammatory, antioxidant, chemopreventative, and neuropreventative activity, as well as...

Article • 3 min read BookmarkBookmark

Medicinal uses of cannabis-based products have been documented for thousands of years. In 1964, Yechiel Gaoni and Raphael Mechoulam identified tetrahydrocannabinol (THC) as a main active component of cannabis. In 1988, Allyn Howlett and William Devane discovered receptor sites in mammalian brains that responded to compounds in cannabis, during a government-funded study at the St. Louis University School of Medicine. In 1992, Devane and researcher Lumir Hanus discovered an endocannabinoid called anandamide and another called 2-arachidonoylglycerol (2-AG) soon after. The same team eventually discovered many other endocannabinoids and cannabinoid receptors.

Listen to our podcast episode about hemp oil, the endocannabinoid system, and cannabinoid health benefits below featuring Carl Germano, RD, CNS, CDN.

What is hemp anyway?

How it differs from CBD & Marijuana

What’s the difference between hemp and marijuana? Between hemp oil and seed oil? Between hemp and CBD? This helpful infographic provides a quick “hemp 101,” useful for a variety of educational situations. Download and print out your free copy today.

View PDF


Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258:1946–1949.

Gaoni Y, Mechoulam R. Isolation, structure and partial synthesis of an active constituent of Hashish. Journal of the American Chemical Society. 1964;86:1646–1647.

Pertwee. Roger. G. (2006). Cannabinoid Phamacology: the first 66 years. British Journal of Pharmacology. Vol. 147. Pages 163-171.

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