Cannabinoids

Cannabinoids are a class of chemical compound naturally present in the flowering plant cannabis, also known as marijuana. The human body also naturally produces a type of cannabinoid called endocannabinoids. Cannabinoids bind to cannabinoid receptors within the body and produce varying effects. This network of cannabinoid receptors is called the endocannabinoid system, which affects the way neurotransmitters are released throughout the brain. Different types of cannabinoids interact with endocannabinoids in different ways.

Hundreds of types of cannabinoids exist, each producing varied effects on the body. The best-known types of cannabinoids include tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main psychoactive compound found in cannabis. CBD is not as psychoactive as THC and studies show it may help alleviate problems such as anxiety, pain, sleep irregularities, and movement disorders. Cannabinoids can also be produced synthetically. Researchers have studied the effects of synthetic cannabinoids in lab setting to better understand how cannabinoids interact in human biological systems. Although some synthetic cannabinoids are used in medications, recreational usage of these compounds is dangerous and can lead to poisoning.

Background

Cannabis plants contain many chemical compounds that serve different roles within the plant. For example, cannabis contains compounds known as terpenes, which create the flavors and aromas of the plants. Chlorophyll is a chemical compound that makes cannabis leaves green. Cannabinoids give the cannabis plant its medical and recreational properties. Cannabis was used as medicine and for recreation by many cultures around the world throughout history. It was especially popular among far eastern cultures and was a major part of the region's folk medicine for many millennia. Cannabis later became a staple medicinal product throughout Europe, being used to treat depression and mental-health problems. The plant eventually made its way west and was used by American settlers and natives as early as 1600. There, it was used to treat headaches, insomnia, pain, and inflammation.

Cannabis's medicinal uses were not studied scientifically until the nineteenth century. Irish physician Sir William B. O’Shaughnessy was one of the first scientists to delve into the effects of cannabis on a person's health. He conducted a number of human clinical trials in the 1830s, during which he cautiously dosed a number of volunteers suffering from various ailments. His studies found that cannabis positively affected individuals suffering from maladies such as cholera, rheumatic disease, convulsions, and alcohol withdrawal. By the late 1800s, cannabis extracts were being sold across Europe and the United States to treat an array of medical problems. One common use of cannabis was to treat stomach pain.

The role cannabinoids played in cannabis's medical properties were not fully understood until many years later. First, scientists had to chemically characterize the many compounds found within the plant. This would require chemical isolation of each active compound. Gradually, chemists came to discover multiple types of chemical compounds within cannabis. One of the first cannabinoids to be isolated by chemists was cannabinol (CBN), which was later revealed to be an oxidation product of other cannabinoids and only available in trace amounts. CBN's discovery paved the way for further chemical isolation of cannabinoids, and soon cannabis's most important cannabinoids had been isolated, characterized, and fully synthesized by researchers. THC became one of the most studied cannabinoids in the years to follow given its psychoactive properties. CBD also became an important cannabinoid that stimulated continued research due to its apparent therapeutic properties.

It took several decades of scientific development to understand how cannabinoids reacted inside the body. By the 1990s, scientists were beginning to understand that cannabinoids acted on specific receptors existing on cell membranes. These receptors became known as cannabinoid receptors. The first THC-binding site, the cannabinoid CB1 receptor, was discovered in 1990. Alongside its psychoactive effects, scientists realized THC was interacting with areas of the brain that controlled sensations of hunger and nausea. Scientists were not always able to identify exact binding sites of the various cannabinoids, however, and it took several more decades to better understand the mechanisms of cannabinoids once they entered the body. By the dawn of the twenty-first century, scientists were still uncertain about the way many cannabinoids acted on the body's interior.

Overview

Cannabinoids are distinguished by their origins. Endogenous cannabinoids are those naturally present in the body. Exogenous cannabinoids are those created outside the body. Exogenous cannabinoids are also referred to as phytocannabinoids when they come from the cannabis plant. The cannabis plant produces 113 known cannabinoids. Among these, the cannabinoids THC and CBD are the best understood, primarily because they are the most prevalent in the plant. Other major exogenous cannabinoids include CBC, CBN, and CBG. Many types of endocannabinoids exist naturally within the body, but the most studied include 2-AG and anandamide

Cannabinoids function within a biological network known as the endocannabinoid system. This system consists of cannabinoids and cannabinoid receptors. Specific cannabinoids bind to specific receptors, much like a lock-and-key system. Once a cannabinoid binds to its receptor site, it causes changes in the cell's function. This in turn leads to varying effects on the body. Two different types of cannabinoid receptors exist, CB1 and CB2. CB1 receptors are manly found in the brain. These receptors create the psychotropic effects of cannabis. CB2 receptors are found in other parts of the body and can affect a number of biological functions. The endocannabinoid system affects a wide range of biological functions and regulates processes related to appetite, pain, mood, memory, sleep, and more.

Exogenous cannabinoids found in cannabis are stored within crystal-like structures of the cannabis plant called trichomes. Trichomes are what give the plant its shine and silk-like appearance. Many strains of cannabis exist and distinct strains contain different amounts of cannabinoids. Most strains contain high levels of THC, which is the psychoactive component of cannabis responsible for the "high" feeling people experience after ingestion. Cannabinoids are ingested in many ways such as smoking, vaporizing, oral ingestion, and topical application. Ingesting cannabinoids causes a range of effects on the body depending on the exact cannabinoid levels present and what cannabinoid is in action. While THC and CBD are the most studied cannabinoids due to their potential health benefits, researchers have found other cannabinoids that also offer health benefits.

THC is the compound most commonly associated with cannabis. It is often the most abundant of cannabinoids present within cannabis and can reach concentrations of up to 30 percent. THC binds to CB1 receptors in the brain. The high caused by THC ingestion creates several effects on the brain, such as feelings of relaxation and euphoria, an increase of certain sensations, distortion of time, increased appetite, and greater sociability. THC also has several affects unrelated to psychoactiveness, such as reducing nausea, vomiting, and pain. THC can cause adverse effects in those who ingest it, and too much THC can cause severe effects such as panic attacks, hallucinations, and vomiting. Other side effects may include dry mouth, dizziness, memory loss, increased heart rate, and bloodshot eyes.

CBD is another major cannabinoid with varying effects, and it has received a great deal of attention for its ability to alleviate certain medical symptoms without producing psychoactive effects. CBD does not usually bind to CB1 receptors and has the ability to reduce the intensity of the psychoactive effects of THC. Studies have shown that CBD may benefit patients experiencing depression, anxiety, and even schizophrenia. It has also been shown to help people suffering from epilepsy and has pain- and inflammation-reducing properties.

Another prevalent cannabinoid found in cannabis is CBC. CBC produces no psychoactive effects and is considered an effective painkiller with antibacterial and antifungal properties. It is also possibly effective as an antidepressant and has shown to be useful in treating acne and diarrhea.

CBG and CBN are not hugely prevalent throughout cannabis but hold great potential in terms of therapeutic use. CBG is actually a building-block cannabinoid for other cannabinoids, producing cannabinoids such as THC and CBD through enzymatic processes. CBG has shown multiple therapeutic effects such as pain relief, reduced inflammation, neuroprotective properties, and antibacterial effects. CBN is unique in that it is not produced by any biological plant processes but is instead a byproduct of THC degradation. Research has shown that CBN has a number of beneficial properties such as anticonvulsant effects, antibacterial effects, and appetite-increasing effects. It also serves as a pain reliever and sedative.

The body naturally produces cannabinoids called endocannabinoids. These cannabinoids are considered endogenous cannabinoids and are distinct from those produced within cannabis. Endocannabinoids share many of the same properties and create similar effects as cannabis cannabinoids. Researchers believe most endocannabinoids function primarily to promote homeostasis within the body, which is the body's balance of its internal conditions. Endocannabinoids have a wide array of functions throughout the body, however.

Scientists have not identified the exact number of endocannabinoids naturally present inside the body, but have isolated several important ones. The most studied endocannabinoids include 2-AG and anandamide. Scientists think that 2-AG plays a role in neurodegenerative diseases and brain injury. Increased levels of this endocannabinoid have been found in patients with Alzheimer's disease and those who have had a stroke. Anandamide is thought to play a role in the feelings of exhilaration experienced after exercise, often referred to as "runner's high." Other effects include improved cognition, mood, and metabolism as well as and reduced pain and inflammation.

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