LeafScience March 17, 2017
Learn more about the endocannabinoid system and how it affects your health.
The endocannabinoid system is a biological system which plays many important roles in the human body. It is also responsible for the physical and psychological effects of cannabis.
Scientists first discovered the system while trying to understand the effects of cannabis, and named it the endocannabinoid system for this reason.
Endo stands for endogenous, which means originating within the body. Cannabinoidrefers to the group of compounds that activate this system.
The endocannabinoid system is a major target of medical research because of its widespread effects and therapeutic potential. While scientists have sorted out the basics of this fascinating system, much more remains to be uncovered.
What are Cannabinoids?
Cannabinoids are the chemical messengers for the endocannabinoid system. While many different cannabinoids exist, they all fall under two categories: endogenous orexogenous.
Endogenous means originating inside the body. Also known as endocannabinoids, these compounds are produced naturally by the human body. They interact with cannabinoid receptors to regulate basic functions including mood, appetite, pain, sleep, and many more.
Exogenous means originating outside the body. The cannabinoids found in marijuana, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), are considered exogenous. When consumed, they also interact with cannabinoid receptors to produce physical and psychological effects in the body.
What are Cannabinoid Receptors?
You may be wondering, what exactly are receptors? As their name suggests, receptors are message receivers. Messages come in the form of chemical messengers binding to the receptor. These messages produce a characteristic effect within the body.
The endocannabinoid system has two receptors: CB1 and CB2. Each receptor responds to different cannabinoids, but some cannabinoids can interact with both.
The distribution of CB1 and CB2 receptors within the body and brain explains why cannabinoids have certain effects.
CB1 receptors are found throughout the body, but are mostly present in the brain and spinal cord. They are concentrated in brain regions associated with the behaviors they influence.
For example, there are CB1 receptors in the hypothalamus, which is involved with appetite regulation, and the amygdala, which plays a role in memory and emotional processing. CB1 receptors are also found in nerve endings where they act to reduce sensations of pain.
CB2 receptors tend to be found in the peripheral nervous system. They are especially concentrated in immune cells. When CB2 receptors are activated, they work to reduce inflammation. Inflammation is an immune response which is believed to play a role in many diseases and conditions.
With respect to the cannabinoids found in cannabis, researchers have found that THC binds to both CB1 and CB2 receptors, activating them just like an endocannabinoid.
CBD does not bind directly to cannabinoid receptors. Instead, CBD works by inhibitingan enzyme called FAAH, which is responsible for the breakdown of anandamide — the most important endocannabinoid in the body. When FAAH is inhibited, it cannot break down anandamide at its normal rate. This leads to a buildup of anandamide in the brain.
What are Endocannabinoids?
Endocannabinoids are cannabinoids produced naturally within the human body. 2-AGand anandamide are the two major endocannabinoids that scientists know of.
Anandamide was the first endocannabinoid to be identified by scientists. Discovered in 1992, its name comes from the Sanskrit word ananda meaning bliss, referring to its unique effects on the mind and body. In 1995, scientists discovered a second endocannabinoid and named it 2-AG (2-arachidonoyl glycerol).
2-AG is found at higher concentrations in the brain, while anandamide is found at higher concentrations in other areas of the body. Both are capable of binding to CB1 and CB2 receptors, but differ in their affinities for these receptors (i.e. how likely they are to bind to and activate each receptor).
Endocannabinoids are “short-order” neurotransmitters, meaning they are synthesized on demand. In other words, endocannabinoids are only produced when the body signals that they are needed, and their presence is transient.
After being released, endocannabinoids are quickly broken down by enzymes, which include FAAH (fatty acid amide hydrolase) and MAGL (monoacylglycerol lipase).
By contrast, when you consume marijuana, large amounts of cannabinoids enter the body and stick around. This means that the endocannabinoid system is activated more strongly and for longer than it would usually be.
There are other endocannabinoids currently under study, including noladin ether, virodhamine, and N-arachidonyl dopamine (NADA). However, their role in the body is not fully understood.
Functions of the Endocannabinoid System
The endocannabinoid system is involved with regulating many basic functions of the human body, including:
- Memory and learning
- Immune function
- Neural development
- Cardiovascular function
Besides maintaining basic functions, the endocannabinoid system also acts in response to illness.
For example, tumor cells have been shown to express more cannabinoid receptors than healthy cells. Studies also show a rise in endocannabinoid levels in patients with various disorders, such as Parkinson’s disease, anxiety, chronic pain and arthritis.
As a result, some scientists believe the overall function of the endocannabinoid system is to regulate homeostasis.
Homeostasis is a key element in the biology of all living things. It is best described as the ability to maintain stable internal conditions that are necessary for survival.
Disease is largely a result of a failure in achieving homeostasis. Thus, the endocannabinoid system’s role in maintaining homeostasis makes it a unique and promising target in medicine.
The Endocannabinoid System in Medicine
Due to its widespread effects in the human body, the endocannabinoid system is believed to hold promise in treating many diseases and conditions. In recent years, scientists have been exploring various ways of targeting this system.
There are currently two major ways of targeting the endocannabinoid system:medical marijuana and synthetic cannabinoids.
Medical marijuana is the most common way of targeting the endocannabinoid system to treat various illnesses. Compounds in marijuana, including THC and CBD, are known to produce therapeutic effects by interacting with the endocannabinoid system.
Medical marijuana can be prescribed for a wide variety of conditions including chronic pain, nausea, multiple sclerosis, epilepsy, and palliative care.
Despite the success of medical marijuana, some users experience unpleasant side effects, such as feeling high. Some people do not enjoy the psychological effects of cannabis, and would prefer a treatment that avoids this.
Synthetic cannabinoids are molecules that are engineered to mimic the activity of existing cannabinoids. These compounds can target the endocannabinoid system in a more specific and efficient way.
For example, Dronabinol is a synthetic version of THC that can be prescribed to cancer and AIDS patients to combat nausea and appetite loss. Cesamet is another synthetic cannabinoid that is similar to THC. It is used to reduce vomiting in cancer patients and for pain management in several disorders including fibromyalgia, multiple sclerosis, Parkinson’s disease, and chronic pain.
Besides mimicking the effects of cannabinoids such as THC, synthetic cannabinoids can also be designed to target specific parts of the endocannabinoid system while avoiding others.
For example, researchers are currently examining whether the endocannabinoid system can be targeted peripherally using synthetic cannabinoids which cannot cross the blood-brain-barrier. This would avoid the negative side effects of cannabinoids entering the central nervous system and affecting the brain (i.e. the feeling of being high).
In sum, the endocannabinoid system is truly a treasure trove for scientists and medical professionals. It is extremely complex, plays important roles in many vital processes, and holds promise as a treatment target for many debilitating conditions.