Our Endo-Cannabinoid System Explained

Certain compounds in our bodies resemble the active ingredients in Cannabis flowers and help us to operate and interact with the world.

Modern science has made many new discoveries about how the human body operates and interacts with the world we live in. As humans, we tend to rely on our senses for correct information about our surroundings, but everything that we know and feel is mediated by chemicals. The information from our senses is chemically-mediated perception, not fact. In addition, most of our life-sustaining activity during the day takes place below the level of consciousness, performed by the subconscious parasympathetic nervous system. We could not survive without these unconscious activities, which are mediated by chemical reactions that would take a chemical factory to produce.

The story begins in the early 1970s. Candace Pert, a brilliant pharmacologist who passed away in September of 2012, was working at Johns Hopkins University. She was investigating why opiate molecules accumulated in brain tissue. Her work led to the discovery of the first receptor site in our nervous system. Receptor sites are places on a cell membrane where a chemical compound can bind and stimulate a series of chemical events in that cell.

The receptor site has a specific shape and molecular composition where chemical compounds with a matching shape and composition can bind. These matching compounds are known as ligands and function as a chemical 'key' switch. The first receptor site accepted a molecule with a chemical structure similar to that of opiate molecules found in the poppy plant. These sites were therefore given the name 'opiate receptors'. When an opiate molecule binds to this receptor site, it stimulates the cell to become a chemical factory that releases specific chemical compounds into circulation. These compounds precipitate relief from painful stimuli and result in feelings of well-being.

Similar receptor sites were located throughout the brain and body that accept opiate-like molecules but release a variety of chemical compounds, or messengers, resulting in a variety of systemic functions. Some of these chemicals function inside the cell. Others are released outside of the cell to travel throughout the body, carrying messages to other cells, nerves and organs. It was soon discovered that the body made its own chemical 'key' or ligand for these 'locks' or receptor sites. This self-made 'key' was an opiate called a neurotransmitter ligand, known as an endorphin. Other endogenous opioid ligands were found and categorized as dynorphins, enkephalins, endomorphins and nociceptin.

This discovery revolutionized and changed neuroscience. No longer did scientists believe and accept that neural activity was due to the anatomical structure of our brain and nervous system. Now it was known that chemical messengers - neurotransmitter ligands - carried messages between cells and organs in the body. These chemical messengers stimulate receptor sites on cell membranes that cause the cell to become a chemical factory, producing compounds that create specific effects altering activity, perception and other body processes.

Receptor sites became a topic of interest in neuroscience, and discoveries were made of new sites with further activities. In 1988, a receptor site for tetrahydrocannabinol, the psychoactive molecule in Cannabis, was discovered in the brain. This receptor site was named CB₁. The existence of this receptor site implied the existence of a naturally-occurring neurotransmitter ligand - an endogenous cannabinoid. This ligand was discovered in 1992 and given the name anandamide (N-arachidonoylethanolamine or AEA) from the Sanskrit ananda, which means 'bliss' or 'delight'. A second cannabinoid receptor site was discovered in our body's nervous system and given the name CB₂.

An additional neurotransmitter ligand was discovered and called 2-AG (2-arachidonoyl glycerol). The receptor sites, cannabinoid ligands made by our bodies that fit into them, and the chemical compounds these ligands stimulate the release of, are all known as our endo-cannabinoid system. Our bodies use dietary omega-3 and omega-6 fatty acids to manufacture the cannabinoids made by our bodies. Hemp seeds are rich in these fatty acids. Because of this structural similarity to THC and other phytocannabinoids (herbal cannabinoids), phytocannabinoids can also fit into the receptor sites in our nervous system. When the receptor site is occupied by a neurotransmitter ligand, a series of chemical processes take place that result in changes in feelings, moods and perceptions, as well as changes in internal body activities and processes.

CB₁ receptor sites are located mainly in the brain and central nervous system, with some also situated in the liver, lungs, kidneys and skeletal system. Stimulation of CB₁ sites is known to produce analgesia and relaxation. CB₁ stimulation triggers appetite, calms nausea and suppresses vomiting. Stimulation at CB₁ sites also has anti-inflammatory properties. Many of these CB₁ effects require some simultaneous stimulation at CB₂ sites. Simultaneous stimulation at CB₂ must be low; otherwise, CB₂ stimulation at too-high levels will block the stimulation at CB₁ sites.

CB₂ sites are located in the immune system on T-cells, macrophages and B-cells. CB₂ sites are found on cells that manufacture blood cells and on embryonic cells before the embryos are implanted in the womb, thus cannabinoids are associated with fertility. CB₂ receptor sites are also found on peripheral nerves. These peripheral receptors are thought to mediate our nervous system's response to pain. Most of the activity mediated through CB₂ receptors is thought to relate to the immune system. The immune system coordinates our body's protective and defensive activities. Research continues.

It is known that stimulation of CB₂ receptors produces changes in endothelial tissue and smooth muscle. Cardiomyocytes and fibroblasts have also shown activity following stimulation of CB₂ sites. Scientists suspect that other cannabinoid receptor sites in the body have yet to be located because of endo-cannabinoid related activities when the CB₁ and CB₂ sites are not targeted.

However, it is still uncertain whether or not cannabidiol binds to CB₂ receptors. CB₁ and CB₂ receptors are also classified as G-protein-coupled receptors. G-protein-coupled receptor sites are the most common type in the brain and nervous system. 'Spice', synthetic smoking material sold as synthetic marijuana, often contains synthetic cannabinoids that produce unknown effects when bound to CB₁ and CB₂ receptor sites.