Science of the ECS

 ECS Overview


The Endocannabinoid System (ECS) is relatively new and recognized as a modulator in endocrine, brain and immune tissue. The system is comprised of endogenous lipid-based ligands known as Endocannabinoids, the receptors they bind (CB1 and CB2) and the biochemical regulators which synthesize or degrade them. Endocannabinoids are synthesized from specific types of Omega 3 and Omega 6 fatty acids. The ECS is a homeostatic regulator controlling energy homeostasis and influencing the food intake centers of the gastrointestinal (GI) tract and central nervous system (CNS).

To better understand the ECSs’ function in the body, lets look at homeostasis. Homeostasis is the balance and steady state equilibrium of internal, physical and chemical conditions maintained by the body. Homeostasis is important for many organs and organisms to survive. Disruption in physiological equilibrium can lead to serious health complications if left untreated. Symptoms can range from headaches, blurry vision, or can be as life threatening as a chest pains and Myocardial Ischemia or cancer.

The ECS regulates homeostasis through lipid synthesis and turnover in adipose tissue and the liver, while also regulating glucose metabolism in skeletal muscle. The ECS is also important for its role in cognition, memory, appetite, immune system response, inflammation, cancer, epilepsy, female reproduction, pregnancy (pre and postnatal development), analgesia, thermoregulation and even physical exercise. Through these endogenous lipids and receptors, the ECS is triggered for its beneficial effects.


ECS History


The Godfather of cannabis research, Dr. Raphael Mechoulam, first identified and isolated tetrahydrocannabinol (THC) in 1964. Historically THC is known for is psychoactive properties. Dr. Mechoulam also isolated cannabidiol (CBD), a non-psychotropic cannabinoid with antioxidant and neuroprotective characteristics. Cannabinoids made in the body (from within) and endocannabinoids. Cannabinoids naturally occurring in plants are Phytocannabinoids.

In 1990, Lisa Matsuda, a molecular biologist at the National Institute of Mental Health, and her colleagues, identified THC-sensitive receptor in lab rat brains. This was the first time the Endocannabinoid system was defined. The endogenous cannabinoid system was named after the plant that led to its discovery. Soon after, Dr. Mechoulam discovered two endocannabinoids: anandamide and 2-arachidonoylglycerol (2-AG). Endocannabinoids are cannabinoids made within the body by the brain. When endocannabinoids bind to cannabinoid receptors, they trigger a cellular response which is diminished or amplified. These cellular responses range from euphoria to anti-inflammatory.



Endocannabinoids are bioactive lipids that have the potential to signal through cannabinoid receptors to modulate the functional activities of a variety of cells. Through proper diet and exercise the body synthesizes these endocannabinoids which have analogous Phyto-cannabinoids like those in Cannabis.

  • Endocannabinoids are endogenous lipid-based signaling molecules that are synthesized or made from dietary fatty acids and bind to specific G protein-coupled cannabinoid receptors CB1 and CB2.
  • The two best illustrated endogenous ligands are anandamide (AEA) and 2-arachindonoylglycerol (2-AG).
    • The others include: noladin ether, dihomo-γ-linolenoylethanolamide, virodhamine, oleamide, docosahexaenoylethanolamide, eicosapentaenoylethanolamide, sphingosine, docosatetraenoylethanolamide, N-arachidonoyldopamine, N-oleoyldopamine and haemopressin.
  • Anandamide AEA is also refered to as Arachidonoylethanolamine.
    • AEA is an endogenous cannabinoid that has a stronger affinity and binds tightly to the cannabinoids CB1 and CB2 receptors.
    • AEA is analogous to the phytocannabinoid THC. THC helps stimulate AEA production.
    • Regulation of sleep pattern and pain maybe partially influenced by Anandamide. In different pain research studies, Anandamide was shown to promote analgesic actions by binding strictly to peripheral CB1 receptors.
    • AEA also plays a role in regulation of metabolism, pleasure and reward.
  • 2-AG is an endogenous agonist of the CB1 receptor. 


Endocannabinoid’s and their chemical structure







Cannabinoid Receptors

  • Phytocannabinoids such as CBD and THC, and the body’s own natural endocannabinoids, anandamide (AEA) and 2-AG, generate effects by binding to and activating the G protein coupled CB1 receptor and the CB2 receptor.
  • CB1 receptors are expressed more widely throughout the body than CB2.
    • The Central Nervous System is abundant with CB1, particularly in the brain where it mediates the infamous effects of the typical Cannabis high (memory blocking, pain control and increased appetite).
    • CB1 receptors are located on either of the two nerve terminals: excitatory, which excite or increase the activity of target neurons, and inhibitory, which inhibit or reduce activity.
    • The ability for CB1 to excite or inhibit the synaptic signal, demonstrates its homeostatic ability, by increasing or decreasing message flow between cells.
    • Stimulating central CB1 receptors induces increase food intake and thereby weight gain. However, this is only seen in acute cases
  • CB2 receptors are more commonly seen in the immune system and are implicated to be involved in pain as well as inflammatory responses.
    • CB2 receptors are also located in the central nervous system and have been shown functioning during certain kinds of inflammatory responses.
    • CB2 expression is most abundant in immune cells, where it is implicated to have innumerable immunosuppressive effects, including inhibition of proinflammatory cytokine production and signaling apoptosis and autophagia in breast cancer.
    • Evidence shows that the CB1/CB2 receptors increase in density during diseased states.
    • The body’s mechanism is to increase the receptor sites during disease states. This allows for more cannabinoids to bind the receptor.
    • The increase in cannabinoids bind to receptors. We then begin to see a decrease in disease symptoms and or inhibition of the progression of disease.




Cannabinoid Degraders

  • Cannabinoids are fatty acids and are therefore broken down broken down by enzymes in the body such as hydrolase or lipase. Once degraded they no longer function.
  • FAAH is Fatty Acid Amide Hydrolase.FAAH degrades AEA near the synapses it activates.
    • Blocking the enzyme FAAH has similar results as increasing the amount of AEA.
  • 2-AG is degraded by MonoAcylGlycerol Lipase (MAGL); it is the main enzyme responsible for inactivating 2-AG.
  • Current studies are working on inhibiting the above enzymes to increase the levels of AEA and 2-AG.




Source: Drug Discovery Today, Vol 22, Issue 1, January 2017





Dr. AdamsScience of the ECS