About the Endocannabinoid System

Each and every one of us is born with an endocannabinoid system. When these systems become imbalanced, disease sets in. Read more about this process below….


Cannabis sativa L. is one of the oldest plants cultivated by man to treat a variety of ailments, but has remained a source of heated controversy throughout its history. Two of the main cannabinoids present in cannabis is tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabinoids are chemical compounds in cannabis that differentially affect the body and mind through their interaction with different receptors within the endocannabinoid system (ECS) in the body. The reason for the robust and wide-spread action of external cannabinoids, like CBD and THC, is because of the endocannabinoid system present within the body, which generates its own cannabinoids, but also recognizes external cannabinoids. This the ECS is responsible for a variety of biochemical and physiological processes.
Of most interest in the realm of exogenous cannabinoids, cannabidiol has been gaining traction in medicine and science due to its unparalleled pharmacological and therapeutic diversity, and minimal adverse effects on the body. CBD has been touted as a panacea for a variety of ailments, with myriad research studies supporting its observed effects through the discovery of its many biochemical targets and effect on the ECS where many of its components operate (Russo, 2007). Although CBD has been utilized in ancient medicine for centuries, it’s only gained notoriety for its pharmacological-level potential in the last decade. Over 1600 scientific articles have been published (Figure 1) on its mechanism of action, and interest in researching this phytocannabinoid is likely to continue to grow exponentially as we learn more.

Pharmacological actions of non-psychotropic cannabinoids:

Cannabidiol (CBD)

CBD is the second most prevalent cannabinoid in marijuana. It is a 21-carbon terpenophenolic compound exclusive to cannabis after its decarboxylation from a cannabidiolic acid precursor (CBDa). Its effects include analgesic, anti-inflammatory, antioxidant, antiemetic, antianxiety, antipsychotic, anticonvulsant, and cytotoxic effects (confined to cancerous cell lines), which are mediated by a wide variety of molecular signaling pathways throughout the body.

The Endocannabinoid system

The endocannabinoid system (ECS) consists of cannabinoid receptors distributed throughout both the central nervous system (CNS) and peripheral tissues of the human body. It is mainly responsible for maintaining homeostasis among bodily systems including but not limited to the: immune, metabolic, cardiovascular / circulatory, musculoskeletal, and central nervous system; the endocannabinoid system is being studied for its potential to be manipulated in order to either inhibit or facilitate certain outcomes related to disease.

Studies suggest that the endocannabinoid system plays a role in neuroprotection and the regulation of the immune system. Regulating immune cells through, “proliferation and apoptosis” (Endocannabinoids and immune regulation), harmful, non-functional cells (such as malignant cancer cells) are reduced while functioning cells are increased. Similarly, receptors of the endocannabinoid system have been shown to play a role in the regulation of inflammation in both the CNS and peripheral systems. In terms of metabolism, receptors in the gastrointestinal tract as well as the hypothalamic nuclei have shown a direct relationship to hunger and satiety signals. Additionally, receptors found in liver and adipose tissue correlate to the formation and reduction of fat. Potential manipulation of such receptors may open up the possibility of treatments for dietary conditions such as eating disorders or obesity. Cannabinoid receptors found in the cardiovascular system have been found to play a role in vasorelaxation and vasoconstriction leading to potential targets to confront issues such as hypertension. With relation to the central nervous system, the area of most concentrated cannabinoid receptors, the endocannabinoid system has a hand in many foundational human activities such as, “pain reduction, motor regulation, learning/memory, and reward”.

Endocannabinoid Deficiency

Given the widespread distribution of receptors in the ECS, it’s not improbably that many different disorders can result from an imbalance in this system. These imbalances may be congenital or acquired. If it’s a deficit originating from birth, it’s possible that genetically-susceptible individuals might produce inadequate endocannabinoids, or that their degradation happens too quickly. The same deficits might be acquired through injury or infection, or potentially nutritional imbalances.

Dr. Ethan Russo, a prominent and well-published cannabinoid researcher, has written a detailed description of the endocannabinoid system, results of a and its efficacy for human health:
“The analgesic and palliative effects of the cannabis and cannabinoid preparation have been amply reported over the past generation. In essence, the effects result from a combination of receptor and non-receptor mediated mechanisms. THC and other cannabinoids exert many actions through cannabinoid receptors, G-protein coupled membrane receptors that are extremely densely represented in central, spinal, and peripheral nociceptive pathways.”

“Endogenous cannabinoids (endocannabinoids) even regulate integrative pain structures such as the periaqueductal gray matter. The endocannabinoid system also interacts in numerous ways with the endogenous opioid and vanillio systems that can modulate analgesia and with a myriad of other neurotransmitter systems such as the serotonergic, dopaminergic, glutamatergic, etc, pertinent to pain. [Russo] has suggested that a clinical endocannabinoid deficiency may underlie the pathogenesis of migraine, fibromyalgia, idiopathic bowel syndrome, and numerous other painful conditions that defy modern pathophysiological explanation or adequate treatment.”

“Furthermore, researchers Steele Clarke Smith and Mark S. Wagner referenced Dr. Russo’s thoughts on why CBD has such a widespread mechanism of action across the body in their 2014 paper (Russo 2004):
“Dr. Russo understood that each neurotransmitter system can have pathological conditions caused by a deficiency: Alzheimer’s dementia attributed to loss of acetylcholine activity, parkinsonism due to dopamine deficiency, depression associated with lowered levels of serotonin, etc.

Thus, he reasoned, should this be any different in the endocannabinoid system, where the endocannabinoid receptors are especially dense? Could an endocannabinoid deficiency – either congenital or acquired – explain the pathophysioloogy of these elusive conditions?”
This seems to be the general tenet underlying the unparalleled therapeutic diversity of CBD and other cannabinoids, and why supplementation with exogenous cannabinoids may help correct imbalances resulting from an endocannabinoid deficiency.