Cannabinoids are a large and diverse group of substances that can be classified in several ways. Still, it is most beneficial to understand the diversity of cannabinoids as follows: endocannabinoids, phytocannabinoids, and synthetic cannabinoids. Clinical endocannabinoid deficiency (CECD) is a medical theory that proposes that a deficiency of endocannabinoids is the underlying pathophysiology of migraines, fibromyalgia, and irritable bowel syndrome. The deficiency may sometimes start in the womb due to maternal obesity. In our latest article we talked about CBD, now find out more about Types of Cannabinoids and Endocannabinoid Deficiency below.
Clinical endocannabinoid deficiency (CECD) is a medical theory that proposes that a deficiency of endocannabinoids is the underlying pathophysiology of migraines, fibromyalgia, and irritable bowel syndrome.
The endocannabinoid system (ECS) is a complex cell-signaling system identified in the early 1990s by researchers exploring THC, a well-known cannabinoid. Cannabinoids are compounds found in cannabis.
Endocannabinoids, Phytocannabinoids and Synthetic cannabinoids.
The main difference between phytocannabinoids, endocannabinoids, and synthetic cannabinoids is that synthetic cannabinoids are entirely artificial and developed in the laboratory.
So what is ECS – endocannabinoid system? The prefix “endo-” means the inside or inner part of something. Internal cannabinoids were discovered by studying the properties of tetrahydrocannabinol (THC – the most well-known abbreviation for the English word “tetrahydrocannabinol”). Compounds have been observed in humans and mammals chemically similar to THC, a phyto-(plant) cannabinoid. THC is the principal psychoactive constituent of the Cannabis sativa plant, more commonly known as marijuana.
Professor Di Marzo, in 1998 summarised the main functions of the ECS as “to relax, eat, sleep, forget and store.”
ECS consists of endocannabinoids (compounds that bind to cannabinoid receptors), receptors (proteins that receive chemical signals from outside the cell), and enzymes (proteins that speed up biochemical reactions). The two main endocannabinoids are arachidonoylethanolamide, nicknamed anandamide from the Sanskrit word for ‘bliss,’ and 2-arachidonoylglycerol (2-AG).
Cannabinoids, naturally occurring chemical compounds in cannabis, can be found in the plant. To help maintain stability and health, these compounds can act directly on or indirectly on cannabinoid receptors. Cannabinoids are absorbed into the body through cannabinoid receptors. These receptors are most often found in the brain and immune system. These are the most prevalent cannabinoids found within cannabis.
Endocannabinoids are a type of natural ligands that bind to cannabinoid receptors. Ligands are molecules that bind to other molecules. In the body, ligands bind to cell receptors and cause changes in the cell. This can be a change in the cell’s behavior or a chemical reaction within the cell.
Endocannabinoids are produced by most organisms in the animal kingdom, as noted in Robert J. Silver’s article “The animal endocannabinoid system”. Both endocannabinoids and cannabinoid receptors form the endocannabinoid system, which regulates various physiological processes such as neurotransmitter release, pain perception, and digestive, cardiovascular, and hepatic functions. That is called Endocannabinoid Deficiency.
The two most common endocannabinoids are anandamide and 2-arachidonoylglycerol. Endocannabinoids act as a key that acts on the primary cannabinoid receptors CB1 and CB2 (which should be thought of as a lock). Causing their activation and subsequent action. CB1 receptors are mainly found in the central nervous system and are responsible for the effects produced by neurological processes and psychoactive ‘secondary’ effects.
CB2 receptors are found primarily in the immune system and regulate immunomodulatory effects (ensuring that cells can fight infectious agents). In addition, CB2 receptors have recently been detected in the central nervous system and microglia cells and are also present in specific neurons. There are also other receptors with which internal cannabinoids interact to regulate the body system.
Phytocannabinoids, the plant (phyto)cannabinoids, are a class of compounds characterized by 21 carbon atoms. Found in nature only in the plant Cannabis Sativa L. More than 113 phytocannabinoids have been discovered, including their acid and neutral forms and transformation products. So only non-psychoactive phytocannabinoids can be synthesized directly by the plant. Therefore, the main phytocannabinoids present in fresh plant material are Δ9-THCA, CBDA, CBGA, and CBCA.
However, the carboxyl group is unstable and easily lost (CO2 evolution) when exposed to heat or light, leading to the conversion into active neutral forms. The acidic phytocannabinoids undergo partial decarboxylation during the biomass drying process. Subsequently, the acidic phytocannabinoids and some of their dynamic neutral conditions (Δ9-THC, CBD, CBG, and CBC) are mainly found in the dry plant material. Once in the animal or human body, they interact similarly to endocannabinoids.
The main difference between phytocannabinoids, endocannabinoids, and synthetic cannabinoids is that synthetic cannabinoids are entirely artificial and developed in the laboratory. An example of a synthetic cannabinoid is dronabinol, the active ingredient in MARINOL®. A medicine supplied in capsules and used in the USA since 1985 to prevent nausea, vomiting, loss of appetite, and weight loss. Another example of a synthetic cannabinoid is nabilone, the active ingredient in CESAMET®. So a drug approved to control nausea and vomiting caused by cancer chemotherapy. Both drugs are approved for these purposes in the USA, UK, Switzerland, Canada, and Spain.
Some CB1 receptor-selective cannabinoids, such as JWH-018 and JWH-073, have been used as psychoactive ingredients in so-called smart drugs that mimic the effects of cannabis. So these drugs are called Spice. There is not much information on the results of synthetic cannabinoids on humans. Although some have already been shown to cause more anxiety and panic attacks than phytocannabinoids. Synthetic cannabinoids have been developed as research tools for cannabinoid research, but they have never been shown to be reliable for human use in clinical trials. In theory, they should never have left the laboratories where they were developed and synthesized.
In the 2018 article “Synthetic cannabinoids dramatically increase aminotransferase levels. Natural cannabinoids do not” (Synthetic cannabinoids severely elevate aminotransferase levels. Natural cannabidiol does not” by Donish Cushing et al. states that synthetic compounds are dangerous. Dangerous because “the human body does not have the tools needed to catabolize synthetic cannabinoids”. Finnaly, this is because the new cannabinoid molecules synthesized are chemically very different from their naturally occurring counterparts. So this means the human body does not have the proper enzymes to break them down, which can be very dangerous.