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How the Endocannabinoid System was Discovered

 Currently, in the United States, forty-six states and three territories  have some form of a medical cannabis program. This has been a long  struggle for advocates, however.  Ever since the inception of the  Marijuana Tax Act of 1937 that effectively banned its use and sale,  which was later replaced with The Controlled Substances Act in 1970, it  has been a slow process in the discovery of how cannabis interacts with  mammalian bodies. Scientists discovered the brain's opiate receptor in  1973, but it was not until 1988 in a government-funded study at the St.  Louis University School of Medicine that Allyn Howlett and William  Devane determined that the mammalian brain has receptor sites that  respond to compounds found in cannabis.  These receptors, named  cannabinoid receptors turned out to be the most abundant type of  neurotransmitter receptor in the brain. 

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Although the legal stature of cannabis as a schedule 1 narcotic  slowed research, it did not prevent it.  The U.S. government put forth  funding toward cannabis research in hopes that it might produce evidence  to support the claims of its deleterious effects, and throughout the  decade of the nineties, many discoveries occurred, within the states,  and across the seas.  In 1990, it was announced that a team lead by Lisa  Matsuda at the National Institute of Mental health had mapped the DNA  sequence that encodes a cannabinoid receptor in the brain. Matsuda was  also able to clone this receptor. This opened doors and lead to the  development in knockout mice that lacked the G-coupled protein receptor.  When THC was administered to the knockout mice it was shown that THC  had no effect, proving THC works by activating cannabinoid receptors in  the brain.

A second cannabinoid named CB2 was also identified at this time,  which takes presence throughout the immune system and the peripheral  nervous system. The discovery of these receptors resulted in the  uncovering of naturally occurring neurotransmitters called  endocannabinoids. In 1992, at the Hebrew University in Jerusalem, Dr.  Lumir Hanus along with American researcher Dr. William Devane discovered  the endocannabinoid anandamide.  The same team later discovered a  second-major endocannabinoid 2-arachidonoylglycerol (2-AG) and went on  to uncover the less known endocannabinoids; homo-gamma-lineleoul  ethanolamide, docosatetraenoul ethanolamide (DEA), and noladin ether  (2-AGE).  Including N-arachidonoyldopamin (NADA), there are over a  handful of endocannabinoids that have been identified, along with  another handful of G- coupled protein receptors that interact with these  endocannabinoids. 

In the pursuit of unearthing the metabolic pathways of  phytocannabinoids and endocannabinoids, scientists came across an  unknown molecular signaling system within the body that is involved in  regulating a broad range of biological functions. This system was named  the endocannabinoid system (ECS). The ECS performs multiple tasks, but  the goal is always to maintain a stable environment despite fluctuations  in the external environment. It is the system that creates homeostasis  within the body. When an imbalance is detected within our internal  environment, the body synthesizes endocannabinoids that interact with  the cannabinoid receptors. This stimulates a chemical response that  works to return the physiological process back to homeostasis. However,  in some cases, there is a deficiency in ECS signaling. This condition is  known as Clinical Endocannabinoid Deficiency. Reasons to as why this  condition occurs ranges from our body not synthesizing enough  endocannabinoids, our bodies not producing enough cannabinoid receptors,  an abundance of enzymes that break down cannabinoids, or outside  sources such as foods and medications that decrease ECS signaling. The  phytocannabinoids contained in cannabis can be used to supplement this  deficiency. By stimulating and supporting your endocannabinoid system  one can find relief from a multitude of illnesses and conditions.



Hanus. Lumir. O. (2007). Discovery and Isolation of Anandamide and Other Endocannabinoids. Chemisty and Biochemistry. Vol. 4. Pages 1828-1841.

Lee, Martin. A. (2012). Smoke Signals - A Social History of Marijuana Medical, Recreational and Scientific. New York, New York: Scribner.

Pertwee. Roger. G. (2006). Cannabinoid Phamacology: the first 66 years. British Journal of Pharmacology. Vol. 147. Pages 163-171.


WRITTEN BY:                Melissa Moore

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