Cannabis and Endocannabinoid System

In 1964, Raphael Mechoulam and colleagues at Hebrew University in Jerusalem isolated Tetrahydrocannabinol (THC) and found it to be the main psychoactive compound in cannabis. In 1988, Allyn Howlett and co-workers at St. Louis University discovered the cannabinoid receptor. Anandamide (N-arachidonoylethanolamine, AEA) was the fi rst cannabislike compound was discovered in 1992. The second compound, 2-Arachidonolygylycerol (2-AG), was detected in 1995. These compounds were named “endogenous cannabinoids or endocannabinoids”. Endogenous cannabinoids are endogenous lipids that employ the cannabinoid receptors. An important feature of these endocannabinoids is that their precursors are presented in lipid membranes. Despite anandamide and 2-AG both containing arachidonic acid, their routes of synthesis and degradation are almost completely different and are facilitated by different enzymes [1]. These endocannabinoids are implicated in different physiological and pathological functions [2,3]. Cannabinoids produce their effects through the activation of distinct G protein-coupled receptors identifi ed as the Cannabinoid receptor type 1 (CB-1) [4,5] and Cannabinoid receptor type 2 (CB-2) [6]. Although AEA and 2-AG have significant differences in receptor selectivity, both endocannabinoids are generated on demand [7-9]. The human body has a cannabis chemical producing factory called the endocannabinoid system. All vertebrate species, including humans, have an endocannabinoid system. The endocannabinoid system is one of the great unknowns of the biology. Fundamentally, it is a neurotransmission system. This endocannabinoid system is contained of endogenous cannabinoids (endocannabinoids), cannabinoid receptors, and the enzymes responsible for the synthesis and degradation of endocannabinoid. It regulates the fl ow of signals that are being sent between cells for maintaining the balance. Endocannabinoids have a short life span. They are prepared and released on demand as a response to a trigger. The triggers include illness, injury, infl ammation and other imbalances. This system regulates several physiologic pathways in the human body such as cardiovascular activity, pain perception, gastrointestinal activity, hormonal regulation, immune function and infl ammation reactions.


Introduction
In 1964, Raphael Mechoulam and colleagues at Hebrew University in Jerusalem isolated Tetrahydrocannabinol (THC) and found it to be the main psychoactive compound in cannabis. In 1988, Allyn Howlett and co-workers at St. Louis University discovered the cannabinoid receptor. Anandamide (N-arachidonoylethanolamine, AEA) was the fi rst cannabislike compound was discovered in 1992. The second compound, 2-Arachidonolygylycerol (2-AG), was detected in 1995.
These compounds were named "endogenous cannabinoids or endocannabinoids". Endogenous cannabinoids are endogenous lipids that employ the cannabinoid receptors. An important feature of these endocannabinoids is that their precursors are presented in lipid membranes. Despite anandamide and 2-AG both containing arachidonic acid, their routes of synthesis and degradation are almost completely different and are facilitated by different enzymes [1]. These endocannabinoids are implicated in different physiological and pathological functions [2,3]. Cannabinoids produce their effects through the activation of distinct G protein-coupled receptors identifi ed as the Cannabinoid receptor type 1 (CB-1) [4,5] and Cannabinoid receptor type 2 (CB-2) [6]. Although AEA and 2-AG have significant differences in receptor selectivity, both endocannabinoids are generated on demand [7][8][9].
The human body has a cannabis chemical producing factory called the endocannabinoid system. All vertebrate species, including humans, have an endocannabinoid system.
The endocannabinoid system is one of the great unknowns of the biology. Fundamentally, it is a neurotransmission system.

Conclusion
An understanding of human cannabinoid pharmacokinetics is important for the enlargement and monitoring of new therapeutic medications. The extensive manifestation and multipurpose functions of endocannbinoid system not only support its promising potential as a drug target for various diseases, but also make the unwanted side effects almost unavoidable. The discovery of an endocannabinoid appetite, nausea and vomiting as well as pleasure and reward [11]. In addition, the CB2 receptors are usually located in the areas of body that are related to the immune system, peripheral nervous system and bone. However, some areas of the body such as heart, gastrointestinal system, liver, reproductive system and skin, express both type 1 and 2 receptors.
Endogenous cannabinoids occur naturally within the body.
In contrast, exogenous cannabinoids are produced externally and seem to be capable of initiating the endocannabinoid system to a greater extent. The exogenous cannabinoids that are commonly found in cannabis are called phytocannabinoids. The phytocannabinoids can be found in hundreds of different plant species, they are present in the highest concentration in the cannabis plant. The cannabis plant is a natural medicine that could assist the balance of endocannabinoid system. However, there are actually 85 cannabinoids in the cannabis plant, along with hundreds of other compounds. Many of the compounds together creates a synergistic effect when all are present.
The endocannabinoid system can become underactive or overactive, which causes the body to malfunction and come out of a homeostatic state. When our endocannabinoid system is not working properly, we might have an imbalance, which can produce chronic medical conditions including epilepsy, autoimmune disease, myofascial pain, migraine, irritable bowel syndrome, complex regional pain syndrome, anxiety and depression, multiple sclerosis and parkinson's disease. Importantly, overactivity or underactivity of the endocannabinoid system has been associated with some disease states. Overactivity of this system might be correlated with obesity and type II diabetes. Previous reports demonstrated that obese people and type II diabetic patients had abnormally increased blood levels of endocannabinoids. Moreover, underactivity of the endocannabinoid system would decrease the ability to maintain homeostasis. The three most clinical endocannabinoid defi ciency are migraines, fi bromyalgia, and irritable bowel syndrome. All of these are associated with a higher incidence of anxiety and/or depression [12]. The number of cannabinoid receptors could change in response. Intensifi cation in the number of cannabinoid receptors are associated with some disease states such as autistic children and depression persons who committed suicide. Diminution in the number of cannabinoid receptors are related to chronic heavy users of THC-rich cannabis.
Phytocannabinoids are cannabinoids found in plants that stimulate these same receptors. The most famous of these are THC (delta-9-tetrahydrocannabinol) and CBD (or cannabidiol). Cannabis is an herb which has a diverse range of cannabinoids and terpenes present. Cannabinoids in Cannabis are extremely alike to those present and naturally produced by the human body. The medical use of cannabis is now legal in several countries, including Canada and most of Europe and the United States. If the cannabinoids and their analogs become therapeutic agents, they are benefi cial for the treatment of chronic conditions. The possibility of accumulative toxicity must be considered. The long-term toxicity of cannabinoids in humans remains principally unknown. The regular use of