The Endocannabinoid System (ECS)
It is only since the 1990’s that the Endocannabinoid system was discovered within the human body. It exists just like an immune system or central nervous system exists in our body.
The endocannabinoid system can be described as an intercellular (between surrounding cells) communication system. The primary function of endocannabinoids is to help regulate our body’s homeostasis (equilibrium). It is a control system that plays a role in processes like modulation of diverse cellular functions through cell signaling, neurotransmitter regulation and pain perception, and the scavenging of free radicals (anti-oxidation) which are natural byproducts of the body’s chemical processes, such as metabolism and associated with cancer and other human diseases.
The endocannabinoid system (ECS) has at least two types of cannabinoid receptors called CB1 and CB2 which are also called G protein-coupled receptors (GPCRs).
These Endocannabinoid receptors can be found throughout the body. CB1 receptors are mainly expressed in the brain. They are enriched in the cerebellum (cognition, coordination), hippocampus (learning and memory), cortex (cognitive function, executive function and control, integration of sensory input), basal ganglia (motor control, planning) ventral striatum (prediction and feeling of reward), amygdala (anxiety, emotion, fear), hypothalamus (appetite, hormone levels, sexual behavior), brain stem and spinal cord (vomiting, pain). They are also found in the central nervous system, immune system and sensory peripheral nerves. CB2’S distribution in the body is almost completely different than CB1 and is most commonly found in cells of the immune system. It is also expressed in keratinocytes (cells that produce keratin), bone cells (osteoblasts, osteocytes & osteoclasts), liver cells, pancreatic cells, and glial cells (cells that protect and insulate neurons).
In the brain and nervous system, endocannabinoids act as neuromodulators. Our body produces a type of signaling molecules known as endogenous ligands (like Anandamide and 2-AG) which binds to these two primary cannabinoid receptors (CB1 and CB2). The primary job of these signaling molecules or neurotransmitter is to fit or "lock" into its own particular receptor, and then to initiate specific physiological responses within the body.
How Does Cannabis Interact With Our Body? The Cannabis Molecules and The Endocannabinoid System (ECS)
Out of the 700+ known compounds in a cannabis plant, Δ9-THC (Delta 9 Tetrahydrocannabinol) and cannabidiol (CBD) are perhaps the best known. These compounds are known as cannabinoids. Δ9-THC is thought to be the main psychoactive cannabinoid responsible for mood alterations, feelings of euphoria, and cognitive impairments that are hallmarks of its effects in humans.
Research now indicates that cannabis molecules like THC, CBD and numerous synthetic cannabinoids (also known as exogenous ligands because they are produced outside of the body) are able to produce the majority of their biological effects by activating the two receptors, CB1 and CB2 by binding or attaching themselves to these receptors in the body, thus either mimicking or blocking the normal function of the neurotransmitter produced by our own bodies and destined for those receptors.
Agonist and Antagonist
Sometimes these cannabis molecules act as agonists that activate or "turn on" the CB1/CB2 receptors and produce a certain biological action, while some act as antagonists that block the receptor function. Sometimes many of these CB1 and CB2 receptors are linked to each other so that activation of one receptor may block the function of another. Therefore, these receptor activations control the proper balancing or functioning of our brain or nervous system, regardless of the receptor being activated by an external drug (like cannabis) mimicking or blocking a neurotransmitter or by the specific neurotransmitter itself. Only in recent decades, has research further demonstrated that THC molecules can be a full or partial agonist at the CB1 and CB2 receptors while CBD, on the other hand, is an antagonist or “turn off” of these receptors. Since THC is an agonist, it activates the cannabinoid receptors and stimulates further downstream activity in the body. And since CBD is an antagonist, it will bind to the receptor but leave it inactive, meaning that no further downstream activity is generated. While THC and CBD each have numerous medicinal benefits when used in isolation, the agonist and antagonist nature of these molecules are providing mounting evidence that for some conditions, using THC and CBD together in specific ratios can have an enhanced physiological effect such as reducing nausea after chemotherapy, reducing cancer pain or increasing appetite for cancer patients.
More research is required to understand what type of cell signals are being generated by these CB1 and CB2 receptors when activated by cannabis molecules, which in effect, kill cancer cells.
Upregulation and Downregulation
Receptors are created (or expressed), by the DNA of the cell which increases (or upregulates) the number of receptors when there are reduced amounts of endogenous or exogenous ligands in the body or decreases (or downregulates) them when the body is exposed to an excessive amount of ligands.
Scientific evidence shows this fascinating phenomenon. When you smoke cannabis, the amount of exogenous cannabinoids in the blood increases and your body will sense that too many CB1 receptors on the cell surface are being bound by the increased levels of cannabinoids. So, the body will self-balance itself and subsequently decrease the amount of CB1 receptors available (downregulate), effectively putting a ceiling on how much the body can be influenced by cannabis.
In a similar way, when our body detects DNA damage which results in increased mutational errors (unprogrammed cell growth – usually a sign of cancer or an aggressive tumor), it makes more receptors available for binding, thus allowing more endogenous and exogenous cannabinoids like THC and CBD to bind to the receptors and exert a physiological action on the body and brain. This is where anti tumoral effects of cannabinoids come into play. A relatively large body of data accumulated during the last decade shows that the levels of receptors in the ECS system and the endogenous ligands (e.g. Anandamide and 2-AG) are increased (over-expressed) in several types of cancerous tumors like Glioblastoma (GBM), Meningioma, Pituitary Adenoma, prostate and colon carcinoma and sarcoma. CB1 receptors were also found to be upregulated in Hodgkin lymphoma cells and in chemically induced cellular Hepatocarcinoma.