The Endocannabinoid System & How It Works

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Not only has cannabis been around for centuries, it’s also been used by humans for centuries. In order to appreciate the endocannabinoid system, we need to first learn and understand exactly how this fascinating body system works. Within the last 50 years or so has there been any kind of scientific understanding as to how exactly cannabis works in the human body. The first plant cannabinoids were discovered in the 1940’s and it wasn’t until 1964 that THC was officially identified and incorporated. 

Once THC was discovered in 1964, that opened up the door for the search of a receptor within the human body in which THC might interact with. It wasn’t until the 1980’s that the first cannabinoid receptors in the human body were characterized. The discovery of these receptors uncovered a whole new string of regulatory mechanisms within the human body, called the endocannabinoid system. The interaction of cannabinoids with the endocannabinoid receptor molecules results in the many psychological effects of cannabis that occur. 

Think of the endocannabinoid system in terms of a spider web. It consists of a network of endocannabinoid receptors organized through the human body-it’s no wonder that it’s a very complex regulatory system. This system has a broad functionality and is found in all complex animals. The endocannabinoid system supports functions such as digestion, immune response, memory, motor response, appetite, blood pressure, pain, protection of neural tissue, and bone growth. With already such an array of functions already discovered, it’s no wonder researchers predict even more psychological processes with which the endocannabinoid system is involved with will eventually be discovered. 

Cannabinoid Receptors 

There are two primary subtypes of cannabinoid receptors in the endocannabinoid system, which are CB1 and CB2. The receptors are found throughout the immune and central nervous systems, as well as within many other tissues such as the circulatory system, brain, endocrine system, gastrointestinal system, urinary tracts, reproductive system, spleen, and heart. Exciting research has discovered new evidence that leads to at least three other cannabinoid receptors within the human body, in addition to CB1 and CB2

Once cannabinoid receptors were found, the next step was to find the substances produced in the human body that were binding to these receptors. The result of this search led to the discovery of the first endocannabinoids, 2-AG and anandamide, which occurred in the early 1990’s. To date, there are five endocannabinoids that have been discovered and isolated. Byproducts of polyunsaturated fatty acids, they are closely related to omega-3 fatty acids. endocannabinoids are not water-soluble because they’re fats, which means they have a hard time moving easily through the human body, therefore making it easy to understand why they are designed to work regionally. 

One such regional activity occurs when endocannabinoids deliver messages across the synapses (gaps between nerve cells). This works by signaling neurons to communicate with each other through the release of neurotransmitters. It’s easy to see that the role of endocannabinoids involved in this synaptic function is very important because they balance the flow of neurotransmitters, which help keep our nervous system running smoothly and efficiently. 

Produced on demand, endocannabinoids are released back across the synapse, brought up into the cells, and then quickly metabolized

Homeostasis 

endocannabinoids appear to go hand in hand with homeostasis (which means maintaining physiological stability) helping to restore imbalances produced by disease or even injury. One interesting theory in regards to the endocannabinoids’ role in pain signaling is that endocannabinoid levels may be responsible for the standard level of pain throughout the human body. Which may explain why cannabinoid-based medicines may help with treating conditions such as fibromyalgia. It may also prove that the constant release of the human body’s own endocannabinoids could have a restorative effect on muscle tightness which occurs in neuropathic pain, inflammation, multiple sclerosis, and even appetite. The value of proper “endocannabinoid tone” throughout the body may prove to be extremely important to our overall well-being

CB1 Receptors 

The CB1 receptor is found throughout the brain and is where endocannabinoids and CB1 receptors combine to form a “circuit breaker”, which then fine-tunes the release of neurotransmitters. The colossal list of brain functions affected by the endocannabinoid system includes: learning, emotions, cognition, memory, and decision-making, as well as anxiety, regulating body movement, anxiety, fear, stress, pain, appetite, body temperature, motor control, sense of reward, and so much more. 

There is one part of the brain that does not have very many CB1 receptors, which is the brain stem. The brain stem is responsible for respiration (breathing) and circulation and is the main reason why cannabis overdoses are not fatal. Psychoactive effects are the direct result of the CB1 receptor activation

The psychological and physical effects that come from CB1 activation is most commonly associated with the ingestion of cannabis

CB2 Receptors 

CB2 receptors are found mainly in blood cells, spleen, and the tonsils. From these regions, the CB2 receptors control the release of cytokines (immunoregulatory proteins) which are linked to inflammation and general immune function throughout the body.  

It’s important to understand that cannabinoid-based medicines can either interfere with or enhance the endocannabinoid system’s stability. Creating drugs that interact safely and effectively with the endocannabinoid system has proven difficult, and drugs that interfere with the functionality of cannabinoid receptors has had mixed success as well. 

Since cannabinoid receptors are scattered so broadly throughout the body, attempting to activate or suppress them for even a single medical purpose can release an assortment of unfavorable activity elsewhere. 

So, it’s only logical that the next step in research was to focus on developing drugs that can interact with cannabinoid receptors and do not cross the blood/brain barrier, in order to prevent some of the serious side effects. It’s thought that these types of side effects may be reduced by limiting the ability of these new drugs to interact with or block these receptors. Other drug possibilities aim to slow down how quickly anandamides (one of the key endocannabinoids) is metabolized. These prospective drugs show hope as treatments for conditions ranging from colitis to cancer. 

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