In this article we will discuss what cannabinoids are. Cannabinoids are compounds related to cannabinoid receptors, which are present in the body of all mammals as part of the endocannabinoid system. Cannabinoids are also found in various plants and especially in hemp, where there are at least 120 different ones (Scherma, Masia, Deidda, Fratta, Tanda and Fadda. 2018.)

Internal cannabinoids are called endocannabinoids and external cannabinoids are called phytocannabinoids. Most of the effects of all cannabinoids are still unknown, but more cannabinoid research is being conducted year after year, and existing studies illustrate that cannabinoids have a lot of health and medical potential. The most researched cannabinoids in hemp are THC and CBD , but nowadays new studies are also being found all the time on CBG, CBN and other phytocannabinoids, as well as acid-form cannabinoids, such as CBD-A , i.e. cannabidiol acid.

Phytocannabinoids in hemp

Hemp cannabinoids are synthesized and stored especially in hairy trichomes, i.e. resin glands, found on the surface of hemp leaves and inflorescences. These trichomes occur in both female and male plants, but the highest concentration is found in the inflorescences of female plants. In addition, cannabinoids are also present in fruit plant pollen. (Atakan 2012) The presence of phytocannabinoids in plants is explained by their properties to control various biotic (insects, bacteria, fungi) and abiotic (drought and ultraviolet radiation) stressors.

Biosynthesis of cannabinoids

In cannabinoid synthesis, more complex compounds are produced from smaller molecules (Marks et al., 2009; de Meijer, 2014). The first step in cannabinoid biosynthesis is the biosynthesis of geranyl pyrophosphate, olivetolic acid, and divaric acid, the precursors of cannabinoid acids. Next, geranyl pyrophosphate and olivetolic acid form cannabigerolic acid (CBGA), and secondly, geranyl pyrophosphate and divaric acid form cannabigerovaric acid (CBGVA), from which all other cannabinoid acids are formed. For example, CBGA becomes THCA , CBDA , CBCA , and CBGAM . CBGVA, on the other hand, forms the cannabinoid acids like THCVA, CBDVA, CBCVA and CBGVAM. The number and ratio of different synthase enzymes determine the cannabinoid profile of different varieties (Marks et al., 2009; de Meijer, 2014). Cannabinoids are acidic in fresh plants and decarboxylated by heat, time and UV light to cannabinoids – From CBDA to CBD and so on. Henceforth, cannabinoids of the cannabidiol (CBD) and cannabichromene (CBC) types can be degraded to cannabielson (CBE) and cannabicyclol (CBL) by oxygen and UV light. (de Meijer, 2014). Cannabinoids of the tetrahydrocannabinol (THC) type also degrade at high temperatures and upon oxidation to cannabinol (CBN).

Classification of phytocannabinoids

Natural compounds combined from hemp with a typical C21 terpenophenol backbone are called cannabinoids. This class of compounds also includes derivatives and metabolites that are also considered cannabinoids. Through cannabinoid research, at least 120 different cannabinoids have been isolated, which can be divided into 11 different categories:

Tetrahydrocannabinol (Δ9-THC) ,
Δ8-trans-tetrahydrocannabinol (Δ8-THC),
cannabigerol ( CBG ),
cannabichromene ( CBC ),
cannabidiol ( CBD ),
cannabinodiol (CBND),
cannabielsoin (CBE),
cannabidiol (CBL),
cannabinol ( CBN ),
cannabitriol (CBT)
and other cannabinoids .

Production of endocannabinoids in the body

Precursors of endocannabinoids include polyunsaturated fatty acids such as arachidonic acid (Omega 6). They are synthesized in postsynaptic neurons as derivatives of arachidonic acid (omega 6), which are obtained mainly from food, but the body can also produce it from linoleic acid (omega 6). Studies show that adding essential fatty acids to the diet increases endocannabinoid levels and the number of receptors. (Osei-Hyiaman et al. 2005, Berger et al. 2001).

Unlike other mediators in the body, endocannabinoids are rapidly synthesized as needed and are not stored as needed. The formation of endocannabinoids occurs through several enzymatic pathways. For example anandamidine in the synthesis, first N-acetyltransferase (NAT) attaches the cell membrane phosphatiphylethanolamine to N-arachidonyl to form N-arachidonylphosphatidylethanolamine (NAPE), which is hydrolyzed by phospholipase D (PLD) to anandamide (Di Marzo et al. 1999). 2-AG, on the other hand, can be synthesized in the body in three different ways. Phospholipase C (PLC) and diacylglycerol lipase (DAGL) contribute to its formation. In addition to arachidonic acid, anandamide is composed of ethanolamine. In 2-AG, on the other hand, ethanolamine is replaced by glycerol, and in virodhamine, ethanolamine is attached by an ester bond instead of an amide bond. Thus, in various endocannabinoids, other compounds have been linked to arachidonic acid by various bonds. (MJ Savolainen, T. Huusko, A. Keränen, S. Lindeman, A. Reponen and H. Koponen. 2004.). Shortly after synthesis, ananadamide is degraded back to arachidonic acid and ethanolamine by fatty acid amide hydrolase (FAAH). In the rat brain, for example, this occurs within minutes (Cravatt et al. 2001). Other enzymes are also involved in this degradation of endocannabinoids, such as monoacylglycerol lipase (MAGL), which is responsible for most of the degradation of 2-AG, and its inhibition increases the amount of 2-AG (Long et al. 2008 and Jokipii 2010.). They also produce various endocannabinoid derivatives in addition to degradation. For example, COX-2 produces prostaglandin ethanolamide and prostaglandin glycerol esters, which are more stable as long-term signal transducers (Kozak et al. 2001 and Savolainen, Huusko, Keränen, Lindeman, Reponen and Koponen 2004).

A few of the more important findings in the metabolism of endocannabinoids are FAAH and MAGL, which, by influencing the amount of activity, can regulate endocannabinoid levels in the body, as they are responsible for the degradation of anandamide and 2-AG. These are affected by different foods, spices, herbs and the medicines targeted at them.

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