The Endocannabinoid System

Read more about this significant biological system that has revolutionized our understanding of healing and brain chemistry.

The endocannabinoid system is an integral biochemical communicative system found within human biology as well as fish, reptiles, earthworms, leeches, amphibians, birds, and mammals. This intricate network of lipid-based retrograde neurotransmitters regulates numerous functions among our physiology. The discovery of the endocannabinoid system was actually the byproduct of cannabis research completed by an Israeli scientist, Raphael Mechoulam. This recent biological breakthrough has created exciting developments in brain chemistry and revolutionized our understanding of healing.

The Stepping Stones in Discovering the Endocannabinoid System

“By using a plant that has been around for thousands of years, we discovered a new physiological system of immense importance. We wouldn’t have been able to get there if we had not looked at the plant,” Mechoulam stated regarding the endocannabinoid system and his cannabis research. The two decades following Mechoulam’s identification and isolation of tetrahydrocannabinol, THC, in 1964 were filled with cannabis learning opportunities. Scientists found a wide array of medicinal and therapeutic effects from cannabis but were not aware of why these benefits were possible. In 1988, the first cannabinoid receptor was found in the brain of a rat by scientists Allyn Howlett and William Devane. These cannabinoid receptors were identified by the pharmacological response they had to marijuana resin. Scientists discovered that these cannabinoid receptors were actually more abundant and prevalent than any other neurotransmitter found in the brain.

The Discovery of Cannabinoid Receptors

In 1990, Lisa Matsuda announced the National Institute of Mental Health’s findings regarding the exact DNA sequence that encoded a THC-sensitive receptor within a rat’s brain. Humans have the same cannabinoid receptor– cannabinoid receptors work as subtle sensing devices that consistently pick up on biochemical cues that flow throughout the cell surroundings. The first identified cannabinoid receptor is named CB1. Scientists were able to map CB1 receptors throughout the brain, specifically, in the hippocampus (memory), cerebral cortex (higher cognition), cerebellum (coordination), basal ganglia (movement), amygdala (emotions), hypothalamus (appetite), and more.

Matsuda also successfully cloned this cannabinoid receptor leading to the discovery of molecules that worked as agonists and antagonists. This breakthrough led to the identification of a second cannabinoid receptor, named CB2, which is predominantly found throughout the immune system and peripheral nervous system. CB2 receptors are also found within the gut, spleen, heart, bones, liver, kidneys, blood vessels, endocrine glands, reproductive organs, and lymph cells. Scientists have concluded that the CB1 receptor regulates psychoactivity while the CB2 receptor mediates immune system response.

The Revelation of Endocannabinoids

In 1992, Mechoulam worked with Devane and Hanus in order to find a naturally-occurring endocannabinoid which attached to the brain cell receptors the same way THC did. They named this endocannabinoid anandamide, also known as the bliss molecule. Anandamide has a wide range of effects including anti-inflammatory and anti-cancerous properties in addition to regulating body temperature, motor function, feeding, and anxiety. In 1995, Mechoulam and his group of researchers discovered a second prevalent endocannabinoid in our biology called 2-arachidonoylglycerol, 2-AG, which attached to both CB1 and CB2 receptors. In addition to helping regulate the same functions as anandamide, 2-AG is believed to act as a messenger molecule that balances the transmission of signals throughout the brain as well as mediating inflammatory and immune responses.     

The Endocannabinoid System and its Interaction with Cannabinoids

By tracing the metabolic pathways of THC, scientists found an unknown molecular signaling system that regulated a wide range of biological functions. Scientists named this biochemical communicative system the endocannabinoid system after the plant that led to its discovery. Dr. John McPartland explained that the endocannabinoid system has been around for over 600 million years, serving a crucial purpose in animal physiology.  

The International Cannabinoid Research Society, ICRS, formed in 1992 to discuss and further research cannabinoids and the recently discovered endocannabinoid system. The research conducted by ICRS was backed by US government grants and has paved the way for current medical strategies for a wide array of pathological conditions. ICRS also discovered that the CB1 and CB2 receptors responded to three cannabinoid agonists– endogenous-fatty-acid cannabinoids, synthetic cannabinoids, and phytocannabinoids from cannabis plants. Utilizing genetically-engineered rodents that lacked CB receptors, researchers proved that cannabinoid compounds can actually alter disease progression.

The Function of the Endocannabinoid System

Numerous experiments resulted in the successful findings that CB-receptor signaling regulates pain, inflammation, analgesia, appetite, gastrointestinal motility, sleep cycles, immune cells, hormones, as well as mood-altering neurotransmitters. The endocannabinoid system regulates every physiological and cognitive process found within our biology, contributing and maintaining our everyday experience.

The endocannabinoid system also plays a crucial role in fertility and the reproductive process. A misfiring in the endocannabinoid system can actually cause numerous issues including miscarriage. High levels of endocannabinoids in breast milk are vital in postnatal development.

How the Endocannabinoid System Interacts with CBD

CBD is a phytocannabinoid found in both marijuana and hemp plants. When CBD is introduced to our systems, the cannabinoid receptors trigger a multitude of biochemical changes regulated by the endocannabinoid system which is found throughout our biology. When our cannabinoid receptors receive signaling from CBD, they promote homeostasis in addition to stopping any excessive physiological activity. This is significant because endocannabinoids are the only neurotransmitters in our body that function in retrograde signaling, a form of intracellular communication that inherently reduces inflammation, relaxes musculature, lowers blood pressure, inhibits immune response, normalizes overstimulated nerves, and dilates bronchial passages.

Biologist Robert Melamede stated, “Endocannabinoids are central players in life’s multidimensional biochemical balancing act known as homeostasis.” Regardless of the source– synthetic, endogenous, or plant-derived, cannabinoids act as a universal anti-inflammatory in the human immune system. There are numerous causes that can throw your body’s immune system off track leading to autoimmune disease or inflammatory disorders– introducing cannabinoids to your endocannabinoid system sparks retrograde signaling which is an inhibitory feedback mechanism that cools other neurotransmitters when they’re firing too fast.  

Endogenous Cannabinoid Deficiency– Why CBD Works

Endogenous cannabinoid deficiency can be a result of numerous things– lack of cannabinoid receptors, insufficient anandamide and/or 2-AG, etc. Each individual has different endocannabinoid levels and sensitivities. Endogenous cannabinoid deficiency can be caused from lack of exercise, poor diet, genetic predispositions, and environmental toxins– scientists conclude that this deficiency develops due to the inability or reduced ability to adapt to chronic stress. Prolonged exposure to chronic stress results in depleted endocannabinoids which adversely impacts physiological processes. Neurologist Ethan Russo and other scientists have hypothesized that “clinical endocannabinoid deficiency” is the underlying cause of migraines, irritable bowel disease, fibromyalgia, and other degenerative conditions.

When CBD is introduced to our bodies, it stimulates our CB1 and CB2 receptors. By mimicking our endocannabinoids and acting as the retrograde messenger crucial in promoting homeostasis, our biology reacts by achieving balance. Endogenous cannabinoid deficiency may be treated by replenishing with phytocannabinoids.

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