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Effect of CBD oils on anandamide metabolism.

2022-03-01
Effect of CBD oils on anandamide metabolism.

The hemp industry is the fastest growing industry in the world today. This is due in part to the endocannabinoid system (ECD), discovered in the 1990s, and the effect that the phytocannabinoids[1] contained in hemp have on it. In today's supplement market, we have access to many types of hemp extracts, commonly referred to as CBD oils. They differ in their composition and production method, e.g. there are isolates, where CBD occurs solo, distillates with a broader profile of cannabinoids or full spectrum products containing all phytocannabinoids including their acid precursors such as CBDA, CBGA, CBCA, CBDVA, etc. As we all know, full-spectrum oils have the most beneficial effect on our body, according to the research which gave rise to the term "entourage effect"[2] or the achievements of experience-based medicine. This begs the question, does it make sense to administer CBD solo, since the so-called full spectrum is better? The answer to this question is not clear-cut; it depends on what effect we expect and for whom the preparation is intended. Nevertheless, the aim of this paper is not to prove which oil is better, but to draw attention to the therapeutic potential we can obtain by inhibiting anandamide metabolism through the phytocannabinoids contained in hemp oils.

As for anandamide itself, whose chemical name is N-arachidonoyl ethanolamide (AEA), it is the best-known endocannabinoid[3]. The highest concentration of this substance is found in the brain and it is synthesised from phospholipids (phosphatidylethanolamine, phosphatidylcholine) located in the inner layer of the cell membrane. However, as far as the origin of the word Anandamide is concerned, the word comes from the Sanskrit phrase ananda meaning delight, bliss. Scientists probably named it this because it is a psychoactive compound, which is why it is secreted during sleep.

The cell has developed as many as four pathways for the synthesis of anandamide, which means that AEA is of great importance to our body. In the cell, anandamide acts as an agonist for cannabinoid receptors, mainly the CB1 receptor[4] and to a lesser extent the CB2 and TRPV1 receptors. By activating the CB1 receptor, anandamide has been shown to have an antiproliferative effect, to enhance apoptosis of various tumour cells, e.g. colon, and to influence repair, metabolic or modulatory processes. Activation of the CB2 receptor also contributes to apoptosis. By activating the TRPV1 receptor, anandamide contributes to increased oxidative stress and calpain activation[5], which also leads to apoptosis of, for example, glioma cells.

 

Endocannabinoids that are not bound to receptors and those that have already fulfilled their role in the cell are degraded. The main enzyme responsible for the metabolism of endogenous AEA is FAAH (fatty acid amide hydrolase). As anandamide has a structural similarity to polyunsaturated fatty acids, in addition to hydrolytic degradation, it can also undergo oxidation with cyclooxygenase-2. Anandamide is metabolised quite rapidly, although endocannabinoid metabolites have also been shown to play an important biological role, in many disease entities or prophylactically, it would be worthwhile to ensure higher levels. So how do we increase intracellular anandamide levels? Research shows that FAAH regulates the intracellular concentration of anandamide, so inhibiting its activity increases the concentration of AEA. To inhibit FAAH activity, an inhibitor must be used, and this is where CBD oils come to our aid. Cannabidiol (CBD) itself is not an agonist or antagonist of CB1 and CB2 receptors but blocks anandamide metabolism by inhibiting FAAH[6] which contributes significantly to its intracellular levels. The second pathway of anandamide metabolism is cyclooxygenase 2 (COX-2), which is also one of the most common factors in the induction of inflammation, when we are sick and take aspirin it is then that we block COX-2. Returning to hemp extracts, scientific research suggests that the compound responsible for inhibiting cyclooxygenase 2 will be the naturally occurring cannabidilic acid (CBDA) in hemp[7].

In addition to endocannabinoid metabolism, the cell has developed another solution for getting rid of excess AEA, which is to dump anadamide into the extracellular space via endocannabinoid transporters (EMTs), where it is further degraded. Nature has also endowed cannabis with such phytocannabinoids, which have an inhibitory effect on these transporters and these are cannabidivarin (CBDV), tetrahydrocannabivarin (THCV) as well as cannabigerol (CBG). If we inhibit the EMTs, the cell will not dump too much anandamide unnecessarily.

Conclusion: by knowing the role of anandamide and following its metabolic pathways, we can conclude that cannabis oils can make a significant contribution to increasing intracellular anandamide concentrations, which can improve health and help many disease entities.

SOURCES / FOOTNOTES

[1] Plant-derived cannabinoids

[2]Entourage effect is a term first used to study the interaction between different compounds present in cannabis, published in the July 1998 issue of the European Journal of Pharmacology. this text was written by scientists including Professor Raphael Mechoulam and Shimon Ben-Shabat and demonstrates the increase in activity of a given cannabinoid due to the presence of another compound, in this case fatty acid esters.

[3] Endocannabinoids are natural compounds that are produced by human and animal organisms.

[4] The CB1 receptor is one of the receptors of the endocannabinoid system others are CB2 , TRPV1 and the G protein-coupled receptors GPR18, GPR55, GPR119. Expression of CB1 receptors occurs primarily in the central nervous system, mainly in centres controlling motor (basal nuclei, cerebellum), memory and learning (cortex and hippocampus), emotions (amygdala), sensory perception (thalamus) and autonomic and endocrine functions (hypothalamus, pons and medulla oblongata). CB1 receptors are also found in peripheral nerve endings and on the surface of fat cells (adipocytes), in the liver, pancreas or skeletal muscle

[5] is a protein belonging to the calcium-dependent, non-lysosomal cysteine protease family. Degradation of the resulting unfavourable substrates under the influence of cytoplasmic calpains contributes to cellular homeostasis.

[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573017/#bib53

[7] https://pubmed.ncbi.nlm.nih.gov/18556441/

Rafał Błażejewski

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