APR 05, 2018 01:31 PM PDT

How the Endocannabinoid System was Discovered

WRITTEN BY: Melissa Moore

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.

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.

 

Sources: 

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.

 

About the Author
  • Currently working with Pharmacannis, a dispensary in Buffalo, NY. Resided in Northern California for the past 15 years working in the cannabis industry as a farmer, breeder, and chemical analyst. Received a bachelor's degree in biology at Keuka College in NY. Studied nursing at Mendocino College in CA, and currently attending University at Buffalo for a Master's of Education in Science and the Public. I have a passion for research with a focus in the field of endocannabinology.
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