The Endocannabinoid System and the Human Body
Key Pieces of the Endocannabinoid System
Throughout the animal kingdom, the ECS plays a crucial role in maintaining homeostasis. Key components of the ECS evolved long ago, and they are found in almost all vertebrate species. A human endocannabinoid system consists of three major components:
Cannabinoid receptors. Found on each cell's surface
Endocannabinoids. An activating molecule that triggers the action of cannabinoid receptors
- Metabolic enzymes. They degrade endocannabinoids after use.
Cannabinoid receptors: what are they, and why are they present in humans? In cells, cannabinoid receptors receive information from outside the cell by listening to the surrounding environment. Transmitting information about changing conditions to the inside of the cell, they trigger the appropriate cellular response. CB1 and CB2 are the two major cannabinoid receptors. Even though these aren't the only cannabinoid receptors found in the body, they were discovered first and remain the best studied.
CB1 Receptors. CB1 receptors are among the most abundant types of receptors in the brain.
CB2 Receptors. There are more CB2 receptors outside the nervous system, such as in the immune system. Both receptors are found throughout the body.
The Endocannabinoid System
How do we manage to maintain homeostasis (i.e., a relatively stable equilibrium between interdependent elements, particularly as maintained by the physiological process) with all the complex signals in our cells, genetic mutations, and outside influences? This is due to the endocannabinoid system (ECS). It is found almost everywhere in the human body and maintains the body's homeostasis. The body achieves this by activating a negative feedback loop through which various cannabinoid receptors (CB) are targeted by endocannabinoids.
G-protein-coupled receptors enable them to directly influence the signals they receive. The function of this signal is to act as an "override", which is different from all other cells. While other cells can modify signals, from amplifying to diverging, a neuron "overrides" those cells. Cell death, for example, would result from a fracture in the toe. As a result, the lymphatic system responds by increasing blood flow and migrating white blood cells to the surrounding regions. In response to the excess lymphatic signals, the ECS recognizes that the inflammation is no longer needed, and the CB receptors in the surrounding immune cells and tissues begin to bind with cannabinoids and to slowly reduce the inflammatory response.
The ECS is made up of multiple endocannabinoids. These can all have anti-proliferative, anti-inflammatory, and anti-metastatic functions. Moreover, they appear to regulate neurotransmitters, the immune system, and mitochondrial function. Endocannabinoids include anandamide and 2-archidonyl glycerol (2-AG). The human body produces anandamide as an endocannabinoid. Known as the "bliss molecule," it can be released when one eats chocolate after cravings.
For controlling pain stimuli, anandamide may be an extremely useful cannabinoid. This is due to the fact that anandamide has an interesting property that determines the type and number of receptors it activates. In addition to its direct effects on memory, anandamide can also make or break short-term connections between nerve cells. The question has been raised whether anandamide also relieves psychological discomfort as well as physical pain. If this is the case, it could be utilized to help those suffering from post-traumatic stress disorder (PTSD). According to De Petrocellis et al. (1998), repression is a well-known coping mechanism. Additionally, anandamide provides anti-proliferative effects on breast cancer cells. There is also evidence for endocannabinoids bind strongly to CB1 receptors, and this could account for the analgesic properties.
The most prevalent endocannabinoid in the human body is 2-arachidonyl glycerol. Its chemical structure is remarkably similar to that of anandamide, only it contains a different R-group. The compound is considered a full agonist of both CB1 and CB2 receptors, which plays an important role in the ECS. The high expression of this gene in peripheral immune cells suggests that it may play an important role in anti-inflammatory processes by suppressing the immune system. Nevertheless, it also acts as an endocannabinoid when it binds to CB1 receptors in the brain.
The Endocannabinoid System and Food Intake Regulation.
Recent descriptions of the endocannabinoid system, both in the central nervous system and in peripheral tissues, indicate that it plays a role in the regulation of appetite, food intake, and energy metabolism.
Body Organs and The Endocannabinoid System
Macronutrient metabolism and energy expenditure are primarily controlled by the gastro-intestinal tract, muscle, liver, adipose tissue, and endocrine system. In addition to producing Endocannabinoids (EC), the digestive tract and its associated organs are affected by the ECS during digestion and absorption of macronutrients. The muscle and liver store glucose, while glycogen and adipose store fat. Additionally, the muscle, liver, and adipose work together to supply intermediates that keep energy balance and growth and maintenance in the fed and fasting states. ECS is clearly a major player in macronutrient metabolism between the organs responsible for food intake and energy balance in the body.
It is due to the endocannabinoid system (ECS) that plant cannabinoids produce certain effects within the body. For example, THC and anandamide are both CB1 activators.
Why aren't we affected all the time? In general, neurotransmitters and cannabinoids are rarely restricted to interaction with one type of receptor; they interact with many different types of receptors.
There are several reasons for this. To begin with, THC does not interact with CB1 receptors in the same way as the body's natural endocannabinoids do. Additionally, the metabolic enzymes that quickly break down endocannabinoids like anandamide do not break down THC, so THC remains active for much longer.
In other words, whereas plant cannabinoids work similar to endocannabinoids, they may interact with a variety of other receptor-based systems and therefore yield specific effects.
Activating the ECS with cannabis or any other substance isn't a catch-all. As with most things in biology, it's complicated. As we learn more about homeostasis, and how the ECS illustrates it at the cellular level, we can gain a deeper appreciation for why we have an ECS in the first place, and how different cannabinoid therapies might actually work. Due to the presence of the ECS across many systems of the body, including the nervous and immune systems, cannabinoid-based interventions appear to be an effective catalyst for the ECS and the promotion of homeostasis within the organism.
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