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The Endocannabinoid System

The Endocannabinoid System (ECS), known as “the body’s own cannabinoid system”,(*)(pb) is located in the mammalian brain and throughout the central (brain and spinal cord) and peripheral (ganglia and nerves outside brain and spinal cord) nervous systems. The ECS is involved in a variety of physiological processes including, but not limited to, appetite, pain sensation, nausea, mood, memory, anxiety and stress, and controlling the psychoactive effects of cannabis.(*) The way the ECS works is by producing specific molecular receptors, proteins released on the surface of cells, that bind with cannabinoids activating neurons and creating electrochemical signals. One useful analogy is the ECS functioning as a lock and key. The receptors represent the lock, and the cannabinoids that bind to them act as a key. When the lock is opened, it creates a neural response, which can lead to a number of physiological responses. Much of how cannabinoids affect us depends on where endocannabinoid receptors are located throughout the brain and body and the concentration of receptors in those areas. The neurotransmission of the endocannabinoid system differs from other neuro-communication in that the signals travel backwards along the synapse, classifying them as “retrograde messengers.” (*)(pb) As a result, cannabinoids and their receptors act as neoromodulatory regulators. They can slow down excitatory electrical signals between neurons (a cause of over stimulation of the brain), or increase signals in other cells; thus, aiding with neuroprotection.

There are two primary receptors and two primary cannabinoids that work together within the ECS. The primary receptors are CB1 and CB2, and their main molecular targets are endocannabinoids Anandamide and 2-Agryclinblahblah (2-AG), which are found mainly in the brain and nervous system, as well as in organs and tissues. (*)(pb)

CB1 Receptors bind with Anandamide and its mimetic phytocannabinoid, Tetrahydrocannibinol (THC). In other words, our bodies naturally produce a compound that is very similar in structure to the cannabis plant’s THC, which both bind to CB1 receptors in similar ways. However, one major difference between Anandamide and THC is their formation. Anandamide is fragile; therefore, it breaks down quickly when it binds to a receptor (a reason why we do not naturally walk around continuously high).(*) THC, on the other hand, has a stronger bond and takes enzymes longer to break it down.(*) As a result, the cell is prohibited from firing signals, which leads to physiological responses including the duration of feeling “high”. The more THC introduced to the ECS, the more receptors are activated, resulting in a number of physiological responses.

CB2 receptors are found primarily outside the brain throughout the body in organs and tissues. They bind with the endocannibinoid sn-2 arachidonylglycerol (2-AG), and its mimetic phytocannibinoid, Cannibidiol (CBD), which are also active with CB1 receptors. (*)(pb/) Just as THC and Anandamide are similar in chemical makeup, so too are 2-AG and CBD. These cannabinoids are known to be involved with the regulation of appetite, immune system functions, and pain management. Introducing higher levels of CBD to our ECS may help strengthen our immune systems and help fight against a number of illnesses.

Further research with cannabis and the endocannabinoid system will undoubtedly lead to the discovery of new endocannibinoids and help define existing compounds and the roles they play within the ECS. As a result, our understanding of how these cannabinoids help regulate physiological responses will continue to advance cannabis in medicine.


-Ryan O'Malley, General Manager at Tahoe Wellness Center - 'Notes on Cannabis'



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