2023-07-25 07:42:43
The reason drugs work in humans at all is because the body already produces countless of these substances that are structurally closely related to the substances that we colloquially refer to as drugs. In the case of cannabis, this is the substance group of cannabinoids. THC, probably the most well-known psychoactive representative of this group, only triggers an intoxication in humans because it docks on the same receptors on which endogenous cannabinoids also act.
The body produces several cannabinoids in order to be able to get high, so to speak, when it is needed, for example when pain relief is required or the emotion happiness is to be generated. A variety of immunological processes are also controlled by cannabinoids. This happens primarily via the CB2 receptor, which is found on immune cells and many other parts of the body. Probably the most well-known endogenous cannabinoid is anandamide. There are also numerous much more exotic ones than N-arachidonoyl dopamine, also called NADA for short.
Chemically related to dopamine
From a chemical point of view, NADA is a special form of cannabinoids. In the body, NADA is synthesized from the well-known hormone dopamine. According to the current state of science, there are 2 synthetic routes by which NADA is produced in the body. Most of it is made by a reaction of dopamine with arachidonic acid. In addition, a small amount is also produced via a chain of reactions starting from the non-essential amino acid tyrosine, in which mainly dopamine itself is produced, but NADA is also produced as an intermediate product.
The effect of NADA unfolds mainly on the CB1 receptors. There it acts as an agonist. It exhibits an inhibition constant Ki of around 0.25, which is several times the potency of THC. In the body, NADA is primarily found in the cerebellum, hippocampus and striatum. Since it also has a dopamine structure in addition to its typical chemical structure, which is known from more well-known cannabinoids, it also has an effect on TRPV1 receptors, which are responsible for the transmission of pain. This receptor is colloquially referred to as the capsaicin receptor because it is the receptor that allows the spiciness of chilies to be perceived as hot and painfully hot.
Important role in pain perception
NADA is mainly responsible for the so-called nociception in the central nervous system. Nociception is the cascade of biochemical reactions by which a pain stimulus is transmitted from its point of origin to the brain. Among other things, activities on the cannabinoid receptors and on the TRPV1 receptors are involved in this signaling pathway. NADA acts there as a neurotransmitter, which docks onto the above-mentioned receptors via an agonistic effect and, depending on its concentration there, is involved in the intensity of the perceived pain.
A research project from 2017, which was carried out at the medical university in Halle (an der Saale), dealt with exactly this role of NADA in the process chain of pain transmission. It was concluded that NADA might play an important role in the search for new painkillers in the future. All painkillers available on the market to date do not regulate the process of pain transmission in the same way as NADA.
Key function in numerous other endogenous processes
NADA acts as an endogenous anti-inflammatory agent. Its anti-inflammatory effect results primarily from the fact that it inhibits PEG2 synthesis. PEG2 is a protein that plays a central role in the development of inflammation. Typical side effects such as redness or fever are primarily controlled by this protein. Consequently, the containment of PEG2 by the endogenous cannabinoid NADA alleviates exactly these inflammatory reactions.
Furthermore, NADA is involved in the regulation of vascular tone. Vessels can either contract or expand and relax due to various influencing factors. Exactly this process is also controlled by CB1 receptors on the vessel walls. NADA is responsible for the relaxing effect via an agonistic effect on the CB1 receptor. It is known from both mouse models and cell cultures that NADA also has a neuroprotective effect.
Especially in the hippocampus, it can reduce the damage of oxidative stress on nerve cells through its agonistic effect on the CB1 receptor. In immune cells, NADA plays a key role in coordinating the immune factor TNF, a cytokine that is also involved in immune responses. All of these examples show that cannabinoids can do much more than just get you high. Rather, they play a central role in a variety of immunological and chemical processes without which our body would not be able to survive.
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#Narachidonoyl #dopamine #endogenous #cannabinoid
