Visualization of the endocannabinoid signaling system (5:08) Published on May 7, 2012 A Masters Research Project submitted for Masters of Science, Faculty of Medicine, University of Toronto. Developed in collaboration with Biomedical Communications, Department of Biology, University of Toronto at Mississauga, The Canadian Consortium for the Investigation of Cannabinoids and with funding provided in part by the Quebec Pain Research Network. Copyright Leanne Chan 2011 youtube/watch?v=jznQfMj9RWM ----------------------------------------------------------------- What Is the Endocannabinoid System? via WiseGeek The endocannabinoid system (ECS) is a set of signaling molecules in the central and peripheral nervous system that helps regulate processes of the body such as appetite, pain, mood, and memory. A signaling molecule is a chemical that passes information from cell to cell. In the endocannabinoid system, these molecules are primarily signaling lipids called endocannabinoids, fatty molecules that bind to receptor proteins to trigger a response. The chemical make-up of endocannabinoids and the responses they elicit are mimicked closely by the drug cannabis, which is sometimes prescribed to trigger an increase in appetite, a lessening of pain, and a lifting of mood. An endocannabinoid is an example of a ligand, or a molecule that binds to proteins in order to generate a signal response. In the endocannabinoid system, these ligands exist within cells in the central and peripheral nervous system. The nervous system is a network of signaling tissues that gathers sensory input, processes this information, and then allows the body to make a coordinated response to the stimuli. The sensory input can be internal or external to the body, sensing factors such as outside temperature, body temperature, blood acidity, blood pressure, sounds, sights, smells, and pressure on the body. The central nervous system includes only the brain and spinal cord, while the peripheral nervous system encompasses all nerve cells outside of the brain and spinal cord. The endocannabinoid system involves two main ligands, anandamide (AEA) and 2-arachidonoylgycerol (2-AG), which are produced and released inside the body in response to an electrical impulse called a depolarization. It is thought that cells produce endocannabinoids as they are needed, rather than having a constant stock within the cell. The ligands are then released into the synapse, or the space between nerve cells, and taken into the next cell. The ligands then bind to two cannabinoid receptors, CB1 and CB2, in order to produce a response. Anandamide prefers to bind with the CB1 receptor, which is mostly located in the central nervous system, but also found in some of the body tissues. The 2-AG endocannibinoid binds equally to both the CB1 receptor and the CB2 receptor, which is located in the peripheral nervous system. There is evidence of a third ligand called noladin ether, which binds more strongly to CB2, though there is debate over whether the substance can actually be called an endocannabinoid. Two other endocannabinoids called N-arachidonoyl-dopamine (NADA) and Virodhamine (EOE) have been discovered recently and bind more strongly to CB1 and CB2, respectively. Both receptors are made of proteins, or chemical compounds composed of amino acid chains, that accept and respond to the release of ligands. These responses in the endocannabinoid system regulate several of the body’s processes, including the sensation of pain, appetite, mood, memory, learning movement skills, and the regulation of the nervous system. Because cannabis contains compounds called cannabinoids that are chemically similar to endocannabinoids, the introduction of cannabis into the body can produce some of the same responses. In the 1980s, it was discovered that chemical compounds within cannabis bind to cannabinoid receptors within the nervous system, much in the same way that endocannabinoids bind to the cannabinoid receptors. The three principle cannabinoids present in cannabis are tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN), but there are many such substances that interact with the endocannabinoid system. Those that bind to CB1 are thought to be responsible for the mood lifting and anti-convulsive qualities of the drug. The cannabinoids that bind to CB2 are thought to contribute to the anti-inflammatory, or anti-swelling, qualities of the drug that help to dull pain. wisegeek/what-is-the-endocannabinoid-system.… --------------------------------------------------------------------- The Endocannabinoid System: An Overview via TruthOnPot March 22, 2013 Marijuana has been used as a medicine for thousands of years with evidence dating back to 2000 BC, but only in the past few decades have scientists truly understood how it works. What led to this understanding was the discovery of the endocannabinoid system – a unique biological system that facilitates the activity of medical marijuana within the human body. What Is The Endocannabinoid System? The endocannabinoid system is a central regulatory system that affects a wide range of biological processes. It consists of a group of molecules known as cannabinoids as well as the cannabinoid receptors that they bind to. Although marijuana is a source of over 60 cannabinoids (including THC and CBD), the human body produces a number of cannabinoids as well. These endogenous cannabinoids include anandamide and 2-arachidonoylglycerol (2-AG) and are present in all human beings. Decades of scientific research on the endocannabinoid system has resulted in the discovery of two types of cannabinoid receptors, CB1 and CB2. These receptors are found in various parts of the body, but are most prominent in the brain and immune system. Cannabinoid receptors act as binding sites for endogenous cannabinoids as well as cannabinoids found in marijuana. When cannabinoids bind to CB1 or CB2 receptors, they act to change the way the body functions. While cannabinoid receptors are primarily expressed in the brain and immune system, researchers have identified cannabinoid receptors in a variety of other places as well, including the peripheral nervous system, cardiovascular system, reproductive system, and gastrointestinal and urinary tracts. Cannabinoid receptors continue to be identified in unique parts of the body as research on the endocannabinoid system progresses. What Does It Do? Interestingly, the endocannabinoid system is not unique to the human species. Rather, research has shown that this system is common to all humans and vertebrate animals – and even some invertebrate animals – suggesting its significance in the process of evolution. Experts believe that natural selection has conserved the endocannabinoid system in living organisms for 500 million years. Although the endocannabinoid system affects a wide variety of biological processes (such as appetite and sleep), experts believe that its overall function is to regulate homeostasis. Homeostasis is a key element in the biology of all living things and is best described as the ability to maintain stable internal conditions that are necessary for survival. Disease is simply a result of some aspect of failure in achieving homeostasis, making the endocannabinoid system a unique target for medical applications. Medical Applications A primary example of the endocannabinoid system’s role in homeostasis comes from research that has identified an overexpression of cannabinoid receptors in the tumor cells of various cancer diseases, including lung cancer, liver cancer, breast cancer and prostate cancer. Research has also shown that tumor growth can be inhibited and even reversed when cannabinoids such as THC are administered. Experts believe that the overexpression of cannabinoid receptors is an indicator of the endocannabinoid system’s role as a biological defence system, providing strong support for the use of medical marijuana. Interestingly, research suggests that this defence system is not only useful in treating cancer, but may also be beneficial in the treatment of a wide variety of conditions. Current evidence points to the endocannabinoid system as being a potential therapeutic target for the following list of disorders: -AIDS/HIV -Alzheimer’s Disease -Arthritis -Cancer -Chronic Pain -Epilepsy -Fibromyalgia -Glaucoma -Multiple Sclerosis -Sleep disorders -Post-traumatic Stress Disorder -And many more… NIH Review In recent years, researchers from all parts of the world have come to acknowledge the vast medical potential of the endocannabinoid system. Summarized in a 2006 review by the National Institutes of Health (NIH): “In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs… modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson’s and Huntington’s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few…” Excerpt from: Pharmacological Reviews (September 2006) The Endocannabinoid System as an Emerging Target of Pharmacotherapy pharmrev.aspetjournals.org/content/58/3/389.long truthonpot/…/the-endocannabinoid-system-an-…/ ---------------------------------------------------------------- Photo: Locations of the Cannabinoid Receptors (red and yellow are densest areas) Left photo: Cannabinoid Receptor 1 (CB1) Source: BBC series Horizons: Cannabis: The Evil Weed? (2009) youtube/watch?v=QGKpbqXwg84 Right photo: Cannabinoid Receptor 2 (CB2) Source: World Molecular Imaging Society Whole-body biodistribution and radiation dosimetry of the cannabinoid type 2 receptor ligand [11C]-NE40 in healthy subjects (September 2013) wmis.org/whole-body-biodistribution-and-radiati…/
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