Endocannabinoid System
Introduction
The endocannabinoid system (ECS) is a complex cell-signaling system first identified in 1989 by researchers exploring the receptor for THC, a well-known cannabinoid compound in marijuana. The discovery pathway to this point is quite interesting, starting with the isolation and identification of plant phytocannabinoids, the search for their receptors, and finally, understanding the role of endocannabinoids in this emerging body system.
Although initially studied in relation to cannabis, the ECS is involved in regulating a variety of physiological and cognitive processes in the body, and its existence predates the discovery of cannabis. The ECS plays a crucial role in maintaining physiological homeostasis. Increased research into the ECS and its interactions with various biological systems may lead to better therapeutic strategies for many diseases that currently lack effective treatments.
The ECS continues to demonstrate the plasticity of the brain. The brain's fluid-like nature contributes significantly to its adaptability, influenced by several key factors:
Grey Matter: This brain region primarily comprises neuronal cell bodies and is crucial for processing information and executing brain functions.
White Matter: Comprising mainly myelinated nerve fibers, white matter connects different brain regions and facilitates the rapid transmission of electrical signals across neurons.
Endocannabinoid Tone: This refers to the activity of endocannabinoids in the brain, which play a vital role in modulating neurotransmission, thus influencing various aspects of brain function and plasticity.\
Spasticity: Although often seen as a pathological condition, spasticity involves exaggerated stretch reflexes and can indicate the brain's adaptive responses to injuries or diseases.
History
The history of cannabinoid research has been marked by significant discoveries that have deepened the understanding of plant-derived and endogenous cannabinoids. This journey of discovery began in 1940 when Dr. Roger Adams and his team at the University of Illinois first isolated cannabidiol (CBD). However, the complete structure of CBD was not elucidated until 1963. Just a year later, in 1964, the psychoactive cannabinoid tetrahydrocannabinol (THC) was isolated and identified by Raphael Mechoulam, marking a pivotal moment in cannabinoid research.
The late 1980s brought about another groundbreaking discovery in the field, the identification of the first cannabinoid receptor, CB1, in a rat's brain in 1988. This finding resulted from work by Allyn Howlett and William Devane, who noted that these receptors were more abundant in the brain than any other neurotransmitter receptor, suggesting their significant role in brain functions. This discovery was the defining moment that led to the realization of the endocannabinoid system.
The early 1990s continued to yield critical insights, with the discovery of anandamide in 1992 by Raphael Mechoulam, William Devane, and Dr. Lumir Hanus. Anandamide was identified as the first endocannabinoid, a naturally occurring compound that binds to cannabinoid receptors. Following closely in 1993, a second cannabinoid receptor, CB2, was discovered. Unlike CB1, CB2 receptors are predominantly found in the immune and nervous systems. They are abundant in various organs, including the gut, spleen, liver, and more, indicating their wide role in bodily functions.
In 1995, the cannabinoid research community recognized another major advancement with the identification of a second major endocannabinoid, 2-arachidonoylglycerol (2-AG). Also discovered by Mechoulam's group, 2-AG is notable for its ability to attach to both CB1 and CB2 receptors, suggesting its broad role in modulating the central nervous and immune systems.
Evolution
It is hypothesized that the ECS evolved nearly 600 million years ago when complex life forms, such as sea sponges, evolved. The ECS receptors, CB1 and CB2, evolved as more complex nervous systems were required to develop other organ systems. In fact, the ECS is present in all vertebrate species.
Primitive life forms have been using endocannabinoids for much longer, but their functions were limited to an intracellular capacity. They mainly regulate cellular stress, such as oxidation and inflammation. This function is still present as endocannabinoids remain pivotal for neuronal protection and cell communication; however, other organ tissues express endocannabinoid receptors and use them to regulate function in addition to cell protection.
The ECS allows our bodies to respond to our environment and regulate bodily functions. However, even the ECS can become overwhelmed or overused during states of chronic illness, leading to dysfunction and the manifestation of symptoms and related conditions. Diet, exposure to toxins, exercise, and lifestyle can impact the ECS.
Physiology
The Endocannabinoid System comprises three primary components: Endocannabinoids, receptors, and enzymes. Put simply, the endocannabinoids are the body's natural chemical signal that interacts with its primary receptor to elicit a cellular response. The enzymes are the proteins responsible for making and metabolizing these chemical signals.
Endocannabinoids: These are naturally occurring lipids in the body, similar to cannabinoids found in cannabis, but produced by our bodies. The primary endocannabinoids are anandamide (AEA) and 2-arachidonoylglyerol (2-AG). These molecules help maintain internal homeostasis.
Receptors: These are sites to which endocannabinoids bind. The two main receptors are CB1, predominantly found in the central nervous system, and CB2, found in peripheral tissues, especially immune cells. An endocannabinoid or phytocannabinoid can interact with these receptors to elicit ECS to respond. Many CB-like receptors respond to cannabinoids.
Enzymes: Responsible for creating and breaking down endocannabinoids. Key enzymes include fatty acid amide hydrolase (FAAH), which breaks down AEA, and monoacylglycerol lipase (MAGL), which degrades 2-AG.
Functions
The endocannabinoid system (ECS) is a unique and pervasive biological system within the human body that plays a critical role in maintaining homeostasis by regulating various physiological and cognitive processes. Its influence extends across a range of body systems, including the nervous, immune, endocrine, gastrointestinal, cardiovascular, and musculoskeletal systems, among others. This article delves into the comprehensive functions of the ECS and its profound impact on health and disease.
The ECS primarily involves two types of cannabinoid receptors, CB1 and CB2, which are activated by endocannabinoids like anandamide (AEA) and 2-arachidonoylglycerol (2-AG). These receptors are distributed throughout the body and are involved in numerous functions:
Anti-inflammation: The ECS modulates immune responses, reducing inflammation across various tissues, especially in the CNS, cardiovascular, and digestive systems.
Neuroprotection: It offers protection against neurodegenerative conditions by supporting neuron survival and promoting repair mechanisms.
Anti-proliferation: The ECS can inhibit the proliferation of certain types of cells, thereby playing a role in cancer prevention.
The Entourage Effect
The entourage effect is a concept in cannabis science suggesting that the various compounds in cannabis (like cannabinoids, terpenes, and flavonoids) work together synergistically to produce a more effective and comprehensive range of effects and benefits than any single compound alone, including THC or CBD. This concept posits that the whole plant, with its full spectrum of chemical constituents, is more beneficial for medicinal purposes than isolated compounds.
Phytochemicals
Cannabis contains many phytochemicals, the most notable of which are cannabinoids and terpenes, which are often tested for on certificates of analysis. Flavonoids, newly researched compounds that promote general wellness through anti-inflammatory effects, are also present. Future research examines the role of volatile sulfur compounds, phenols, sterols, and triterpenoids. Phytochemicals are found in all plants, making fruits and vegetables a valuable dietary component for ECS support.
Cannabinoids: These are the most studied compounds in cannabis. While THC and CBD are the most well-known, many other cannabinoids like CBG, CBN, and THCV contribute to the entourage effect.
Terpenes: These are aromatic compounds found in many plants, including cannabis. Terpenes such as myrcene, limonene, and pinene not only influence the scent and flavor of cannabis but also affect its therapeutic properties. For example, linalool helps with relaxation, and caryophyllene offers extra anti-inflammatory effects.
Flavonoids: These are compounds found across the plant kingdom that contribute to pigment, flavor, and antioxidant effects. In cannabis, flavonoids like cannflavin A and cannflavin B are unique and contribute anti-inflammatory properties.