The Endocannabinoid System

April 16, 2025

Probably one of the most important discoveries of our time. THE ECS.

This sub-cellular receptor system resides within all animals that have a spine. It’s a six hundred million-year-old messenger and receptor system integral to homeostasis (the management of balance within your BODY).

There is not a single function in our bodies that is not somehow influenced or modulated by the ECS. You can think of it as a switchboard functioning in and across all physiologic processes and organs, acting and reacting to internal and external stimuli to direct, correct, and overall manage your health.

The ECS regulates everything from relaxation to eating, sleeping, inflammation and even cognitive function. In a nutshell, the ECS is responsible for making sure the entire body is working optimally.

The ECS maintains the bodies’ homeostasis, acting as a chemical bridge between the mind and body. It maintains a stable internal environment, despite an ever fluctuating external world. It regulates blood sugar, immune functions, muscle and fat tissue, hormones, pain centers, reward centers, and metabolic functions. It maintains the heart steady beat, the stomach’s digestion, the lungs, and at the speed of which bones heal. It enables us to forget pain and rewards us for eating and even having sex.

Cannabinoids are also found at the intersection of the bodies various systems, which allow the different cells to communicate. When an injury occurs, cannabinoids decrease the release of activators and sensitizers from the injured tissue, stabilize nerve cells by opening potassium channels to prevent excessive firing, calms immune cells in the areas to slow the release of inflammatory substances.

Broadly speaking, these Neurotransmitter systems can be compared to cell phone networks. The brain send signals and electrical impulses that Commands cells to communicate with each other. What’s more is that it communicates with cells and 2 directions. Not only to Command, but also to transmit signals back to the brain.

Discovery of cellular membrane cannabinoid receptors occurred in the 1990s, when cannabinoid receptor type 1 (CB1) was found at the synapses of the central nervous system and the sensory neurons’ peripheral terminals. CB 1 receptors are expressed in abundance in the hippocampus, cortex, basal ganglia, cerebellum, and spinal cord. These account for cannabinoid effects on memory, cognition, and movement.

CBD and other cannabinoid products have been shown to positively regulate your ECS addressing issues such as anxiety, insomnia, chronic pain, and inflammation.

Here is what the ECS system is known to do:

Body: Stimulates an anti-inflammatory response which helps reduce all forms of chronic aches and pains. Regular use also helps support joint health, mobility, and flexibility
Brain: Helps positively regulate mood patterns which help reduce anxiety and stress. It also promotes better sleep cycles and in some cases may offer a safe remedy for depression and bipolar disorders.
Age: Inflammation is a natural killer responsible for all sorts of disease such as diabetes, heart disease, cancer, and more. Inflammation is also a positive mechanism used to heal damaged tissue. The ECS is a critical part of managing the parts of the body that when finely tuned can help you feel you

In addition to regulating our internal and cellular homeostasis, cannabinoids can influence a person’s relationship with the external environment. Socially, the administration of cannabinoids (especially THC) can alter human behavior, often promoting sharing, humor, and creativity. By mediating neurogenesis (the growth of new brain cells), neuronal plasticity (forming new connections between brain cells), and learning, cannabinoids may directly influence a person’s open-mindedness and ability to move beyond limiting patterns of thought and behavior from past situations. Reformatting these old patterns is an essential part of health in our quickly changing environment.

As we continue to sort through the emerging science of cannabis and cannabinoids, one thing remains clear: a functional cannabinoid system is essential for health. From embryonic implantation on the wall of our mother’s uterus to nursing and growth to responding to injuries, endocannabinoids help us survive in a quickly changing and increasingly hostile environment. A body of evidence is now emerging that links endocannabinoid deficiency to a variety of diseases, including migraine, fibromyalgia, irritable bowel syndrome, and even infant colic.

As I realized this, I began to wonder: can an individual enhance his/her cannabinoid system by taking supplemental cannabis? Beyond treating symptoms, beyond even curing disease, can cannabis help us prevent disease and promote health by stimulating an ancient system that is hard-wired into all of us?I now believe the answer is yes. Research has shown that small doses of cannabinoids from cannabis can signal the body to make more endocannabinoids and build more cannabinoid receptors.

This may be why many first-time cannabis users don’t feel an effect, but by their second or third time using the herb they have increased cannabinoid sensitivity and are ready to respond. More receptors increase a person’s sensitivity to cannabinoids; smaller doses have larger effects, and the individual has an enhanced baseline of endocannabinoid activity.

My 10+ years of experience has lead me to believe that small, regular doses of cannabis might act as a tonic to our most central physiologic healing system.

DISCOVERY OF THE ENDOCANNABINOID SYSTEM

THC was isolated in 1964, but the discovery of the endocannabinoid system began in 1988 when researchers first discovered the CB1 receptors, followed by anandamide in 1992, then the CB2 receptor and 2-AG. (Devane, Dysarz, Johnson, Melvin & Howlett,(1988); Devan, Hanus, Breuer, Pertwee , Stevenson, Griffin, Gibson, Mandelbaum, Etinger, & Mechoulam (1992).

DISCOVERY: RECEPTORS

(GW Pharmaceuticals, 2014; Sulak, 2015a)

CB1 receptors are also sparsely found in peripheral nerves, as well as non-neuronal tissue like fat, muscle, and body organs.
Cannabinoid receptor type 2 (CB2) was found a few years later, predominantly in the immune system and its related structures.

(GW Pharmaceuticals, 2014; Sulak, 2015a).

THE ENDOCANNABINOID SYSTEM (ECS):

Signaling system composed of:

Cellular cannabinoid receptors CB1 and CB2 (most studied) but we’ve come to find there are 8 receptors systems in the body now!
Endogenous agonists of the receptors, mainly anandamide (N‐arachidonoyl‐ethanolamine) and 2- AG (2‐arachidonoyl‐glycerol). These are the physiological ligands that the body produces for the endocannabinoid receptors, and they create similar effects to cannabis in the body.
Enzymes and proteins that regulate endocannabinoid levels through degradation and inactivation of the endocannabinoids.

THE ENDOCANNABINOID SYSTEM (ECS): FUNCTIONS

The ECS’ main role is to maintain homeostasis (Sulak, 2015a).
The ECS controls central and peripheral nervous systems, and other mammalian physiology such as energy uptake, immune response, processing and storage, reproduction, and cellular fate (DiMarzo, 2011).

ECS

Ligands are small signaling or messaging molecules that bind to the ECS receptor: including human and animal endogenous production of endocannabinoids (anandamide and 2-AG), phytocannabinoids (from plant sources), and synthetic cannabinoids (manufactured) (GW Pharmaceuticals, 2014).
Many cannabinoids have been isolated in the plant cannabis, as well as in other herbs like echinacea (Sulak, 2015a).

KEY STRUCTURE AND FUNCTION OF THE ENDOCANNABINOIDS

Local cell signaling: Paracrine (cell communication> influences behavior or differentiation of cells) and EC are also autocrine (chemical can bind to the same cell that produced it).
Retrograde activity in brain: travel “backwards” from post-synaptic to pre-synaptic.
Synthesized on demand (not stored).
Very short half-life.
FAAH (fatty acid amide hydrolase) degrades endocannabinoids.

(DiMarzo, 2011; Griffing & Thai, 2015)

BASIC NEURONAL ACTIVITY OF ECS

Backward system; post synaptic neuron is activated>EC are made from fat cells in the neuron>which travel backward to presynaptic neuron>attaching to cannabinoid receptors at the presynaptic site.

This allows for control of what happens next, such as limiting the amount of neurotransmitter released. The EC therefore regulates how messages are sent, received, and processed

HOMEOSTASIS IN THE BODY

Cannabinoids help create balance via:
Inhibition and excitation of the nervous system
Bone formation and resorption
Inflammatory/ anti-inflammatory signaling
Fat storage and release
Supporting the management of blood sugar levels, blood pressure, and hormone levels

(Vipperman, 2014)

Ways to stimulate your ECS w/o cannabis

ECS-Enhancing Foods include:

Hemp seeds and hemp oil
Flax seeds (grind at home in a coffee grinder) and flax oil
Chia seeds
Walnuts
Sardines and anchovies
Dark Chocolate
Herbs/Tea
Flowering Greens

ECS-Enhancing Activities include:

Social interaction
Unstructured play time (this is important for adults too!)
Meditation
Massage
Osteopathic Manipulation (OMT)
Acupuncture
Breathing exercises
Any voluntary and enjoyable exercise

More resources:

REFERENCES

Devane, W.A., Dysarz, F.A., Johnson, M.R., Melvin, L.S. & Howlett, A.C. (1988). Determination and characterization of a cannabinoid receptor in rat brain. Molecular Pharmacology,34, 605-613.

Devane, W.A., Hanus, L., Breuer, A., Pertwee, R.G., Stevenson, L.A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A. & Mechoulam, R. (1992). Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 258, 1946-1949.
.DiMarzo, V. (2011). Endocannabinoid system. Wiley Online Library. DOI:10.1002/9780470015902.a0023403

Griffing, G.T. & Thai, A. (2015). Endocannabinoids. Retrieved from http://emedicine.medscape.com/article/1361971-overview#a4

GW Pharmaceuticals. (2014). Research history. Retrieved from http://www.gwpharm.com/Research%20History.aspx
Lane, S.D>, Cherek, D. R. Lieving, L.M., & Tcheremissine. (2005). Marijuana effects on human forgetting functions. Journal of Expirmental Analysis of Behavior, 83(1), 67-83.
Manzanares, J., Julian. M., & Carrascosa, A. (2006). Role of the cannabinoid system in pain control and therapeutic implication for the management of acute and chronic pain episodes. Current Neuropharmacology, 4(3), 239-257.
National Cancer Institute. (2015). Cannabis and cannabinoids for professionals. Retrieved from http://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_3

Nimbin Hemp. (nd). The endocannabinoid system neuron interaction (image). Retrieved from https://nimbinhemp.com/wp-content/uploads/2012/07/endocannabinoid-diagram-2-480×454.jpg

Patel, S., Roleke, C.T., Rademacher, D.J., Cullinan, W.E., & Hillard, C.J. (2004). Endocannabinoid signaling negativity modulates stress-induced activation of the hypothalmic-pituitary-adrenal axis. Endocrinology, 145(12), 5431-5438.

Shrivastava, A., Kuzontkoski, P.M., Groopman, J.E., & Prasad, A. (2011). Cannabidiol induces programmed cell death in breast cancer cells by coordinating the cross-talk between apoptosis and autophagy. Molecular Cancer Therapeutics, 1161-9.

Sulak, D. (2015a). Introduction to the endocannabinoid system. Retrieved from http://norml.org/library/item/introduction-to-the-endocannabinoid-system
Sulak, D. (2015b). Endocannabinoid enhancing foods and activities- From Dr. Dustin Sulak. Retrieved from http://www.youtube.com/watch?v=f15ZIrxWOIY
Viperman, M. (2014). What does marijuana do? It rebalances everything. Retrieved from https://michaelvipperman.wordpress.com/2014/04/20/what-does-marijuana-do-it-rebalances-everything

The Endocannabinoid System

Ways to stimulate your ECS w/o cannabis

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