The endocannabinoid system

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התפתחות המערכת האנדוקנבינואידית

The cannabis plant works in the body thanks to a system of receptors responsible for regulating and controlling the various areas of the body and the brain. Our body is actually a “cannabis manufacturing facility” and produces materials similar to those in the plant.

The endocannabinoid system supports the immune system, regulates neural conductors, and affects the functioning of the body in a variety of ways.

The endocannabinoid system developed millions of years before cannabis was discovered in the world, but was discovered only in recent years.

In 1988, the endocannabinoid system, containing receptors, receptors, to which the cannabinoids in the cannabis plant were attached.

In 1990, the first receptor CB1, to which THC was associated with the cannabis plant and its counterpart in the human body, was discovered. Anandamide was discovered only in 1992. Anandamide is an endocannabinoid that acts very similar to the psychoactive component of the cannabis plant!

Anandamide was named this by Professor Raphael Meshulam because the word “ananda” in Sanskrit meant “happiness” and Prof. Meshulam saw experiments in mice because anandamide levels decreased during depression.

Anandemide is produced in the body as needed. In 1993 the second cannabinoid receptor CB2 was detected.

Experiments in mice that eliminated the CB2 receptor have been shown in studies to show that the presence of the receptor and endocannabinoids that bind and activate it are very important in treating and preventing a variety of diseases:

Allergies and autoimmune diseases, addictions, nervous system diseases, post-trauma, liver disease and metabolic diseases as well as weight gain. It is still not known enough to treat people in all these diseases, but it seems that the endocannabinoid system plays a very important role without which we are very ill.

Although they caused the mice to be without the receptors, they saw that endocannabinoids were still activated and concluded that there were other receptors activated by endocannabinoids.

In 1995, another 2K endocannabinoid was discovered in amino acid structure very similar to receptor CB1.

In 1997, the GPR18 receptor was discovered

1999, it was found that TRPV1 was activated by endocannabinoids and in the same year also discovered GPR55

In 2002 they discovered 5HT3 and in 2003 discovered GPR119.

In 2005, PPARs and GlyRs were found to be directly activated by endocannabinoids

2006 GPR119 and GPR18 were activated by endocannabinoids after years of “orphanage” and it was not known who operated them. Anandamide appears to be acting on GPR18, but it is actually an anandamide metabolite called N-arachidonyl glycine (NAGly).

GPR18 is very pronounced in the spinal cord, small intestine, immune system cells, spleen, bone marrow, thymus gland, lungs, testes and cerebellum.

GPR18 can lower blood pressure. It also has significant roles in the migration of immune cells.

GPR55 was activated by endocannabinoids anandamide and 2AG, but its main ligand was found to be lysophosphatidylinositol (LPI), which is expressed mainly in the central nervous system, adrenal glands, gastrointestinal tract, lungs, liver, uterus, bladder and kidneys. GPR55 regulates metabolism, which can affect diseases such as obesity and diabetes.It also has a role in bone cells with a possible role in osteoporosis.GPR55 is a neurotransmitter, -Protective and reduces nerve degeneration in MS models.

The expression of GPR119 is limited to a small number of tissues. Mainly found in the pancreas and digestive tract – suggests that its role is regulation of energy and metabolism. Endocannabinoid, which is most commonly activated, is OEA with very little activity of anandamide and 2AG. Activating this receptor reduces food intake, improves blood sugar, and reduces body weight. These effects are probably mediated by hormones such as GLP-1 insulin.

Transient receptor potential vanilloid 1 (TRPV1) is primarily found in the sensory nerves and in the brain, which responds mainly to heat and inflammation and sends a signal to the brain, the most common known receptor of this receptor is capsaicin, the component found in hot pepper that causes burning pain. A chronic pain problem Anandamide also activates this receptor with a different effect in the brain – as a pain reduction and in the sensory peripheral nervous system may be increasing the feeling, not yet clear.

Serotonin receptors – there are many but 5HT3 is unique because it is not a GPCR but an ion channel.

Very well known for his connection to nausea and vomiting in the base due to chemotherapy treatment. Anandamide binds well to this receptor and therefore Anandamide’s corresponding THC helps prevent nausea and vomiting.

GlyRs are also ionic receptors that suppress the transmission of pain from the spinal column to the brain.

(Peroxisome proliferator-activated receptors) PPARs differ from all the receptors I have described so far, since instead of being in the cell membrane it is inside the cell and can bind to DNA sequences and change transcription of the target gene.There are three forms of this receptor α, β,..

Anandamide and 2AG can activate a PPARα receptor but OEA and PEA are more effective in activating this receptor. Anandamide and 2AG can also activate the PPAR..

Some of the PPARα and PPAR רצ receptors are associated with protection of the nervous system, protection against ischemia, decreased nicotine addiction, anti-inflammatory drugs, weight loss, vasodilation and cancer.

There are already approved drugs for the treatment of diabetes in insulin resistance (PPAR)) and metabolic syndrome, for lipid lowering (PPARα).

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