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How does marijuana affect and act on the brain and nervous system?

How “Cannabis” Works in the Human Body

It should be known that there are 11 major organ systems in the human body, including the circulatory system, respiratory system, urinary system, reproductive system, integumentary system, skeletal system, muscular system, nervous system, endocrine system, lymphatic system, and digestive system. Work under the synergy of the system and maintain the continuation of human life. When it comes to the topic of how “cannabis” works on the human body, it is important to briefly introduce a little-known but crucial system in the human body-the endocannabinoid system, which to some exis arguably the most important physiological system involved in the establishment and maintenance of human health.

Each of us has an Endocannabinoid System (ECS) in our body. The so-called “endogenous” is endocrine, that is to say, the human body can secrete and produce cannabinoids by itself, and use them to participate in the establishment and maintenance of human health and various functions. So how does the body use the cannabinoids produced by this system? There is a special protein called cannabinoid receptor in the human body, which can bind to specific signal molecules outside the cell, and then activate a series of biochemical reactions in the cell so that the cell has a corresponding effect on external stimuli.

Cannabinoid Receptors

CB1 receptors are mainly located in the brain, spinal cord, and peripheral nervous system, also known as central cannabinoid receptors. Its activation can reduce the release of neurotransmitters, such as dopamine and GABA, which are involved in the regulation of memory, cognition, and motor control.

CB2 receptors are mainly distributed in the periphery, such as the marginal zone of the spleen, immune cells, tonsils, thymus, etc., also known as peripheral cannabinoid receptors. Studies have shown that CB2 receptors are also distributed in the hair epidermis and hair follicle tissue of rats, and may be involved in some physiological and pathological processes of the skin. 

It consists of 360 amino acids, although much shorter than CB1, but still a typical G protein-coupled receptor. Its roles mainly include the regulation of cytokine release and immune cell migration in and out of the central nervous system. The study found that CB2 cannabinoid receptors also have a protective effect on the nociception of thermal stimulation.

It can be seen that the common role of CB1 receptors and CB2 receptors is to regulate the release of chemical transmitters, but CB1 receptors are mainly derived from nerve cells, and CB2 receptors are mainly derived from immune cells. In addition to CB1 and CB2 receptors, some other types of cannabinoid receptors have been observed, but they have not been cloned and their active roles are not well understood.

From the above content, we learned that the endocannabinoid system (ECS) is a signaling system in the human body, mainly composed of cannabinoid receptors CB1 and CB2, and those paired with these two receptors are called endogenous Cannabinoids, such as N-arachidonoylethanolamide (Anandamide, AEA) and 2-arachidonoylglycerol (2AG), and associated enzymatic mechanisms, including transporters, biosynthetic enzymes, and degradative enzymes. ECS was not discovered until 1992, and scientists have only studied it in detail in the last dozen years.

The cannabinoid receptors CB1 and CB2 are both G protein-coupled receptors. CB1 receptors are mainly found in the central nervous system, with low or moderate expression in the peripheral nervous system. CB2 receptors are mainly found in the immune system, with lower levels in the central nervous system. Scientists discovered endocannabinoids soon after learning about the properties of cannabinoid receptors. The two main known endocannabinoids are N-arachidonoylethanolamide and 2-arachidonoylglycerol. Both are derived from arachidonic acid. 

Many other endocannabinoids were later discovered, such as N-arachidonate, N-arachidonic glyceryl ether, and O-arachidanolamine. Studies have found that the ECS is altered in many diseases, such as multiple sclerosis and spinal cord injury, neuropathic pain, cancer, atherosclerosis, stroke, myocardial infarction, hypertension, glaucoma, obesity-metabolic syndrome, and osteoarthritis Osteoporosis, etc., so new treatments can be developed to restore the normal function of the ECS.

Currently, “cannabinoids” refer to the more than 100 natural compounds from “cannabis,” as well as other synthetic compounds that interact directly or indirectly with cannabinoid receptors. Cannabinoids can be divided into phytocannabinoids.

Sources and Cascades of Phytocannabinoids

The flowers and leaves of “cannabis” contain more than 130 cannabinoids and are also the main source of cannabinoids. Most m cannabinoids have high medical and medicinal value, of which only tetrahydrocannabinol (THC) is hallucinogenic and addictive. To understand these cannabinoids, we first need to understand the “transformation relationship” between them.

CBGA is the chemical precursor to THCA, CBDA, CBCA, and “enzymes” in the cannabis plant convert CBGA into THCA, CBDA, and CBCA. These components are then “decarboxylated (activated) ” by “light or heat” to produce THC, CBD, or CBC, which in turn are converted into other cannabinoids.

Several common cannabinoids

After understanding the source, cascade reaction, and decarboxylation process of various cannabinoids, I believe that everyone must have a basic concept of how CBGA derives many cannabinoids. So, next, Zarro will take you to know some of the most widely used cannabinoids.

Tetrahydrocannabinol (THC for short)

Tetrahydrocannabinol (THC), also known as Δ9-tetrahydrocannabinol (Δ9-THC), Δ1-THC (according to the old nomenclature), is one of the cannabinoids, the main psychoactive substance in cannabis and is known A type of cannabinoid found in the resin glands of dried cannabis flowers in females. In the raw state of cannabis, tetrahydrocannabinol (THC) exists in the form of an acid called tetrahydrocannabinol carboxylic acid (THCA). Male cannabis plants also produce small amounts of THC, but in very small amounts.

Pure THC is a glassy solid at low temperatures, and its viscosity gradually increases as the temperature increases. THC is an aromatic terpenoid, so it is hardly soluble in water, but easily soluble in most organic solvents, especially lipids and alcohols. In the 1760s, Israeli chemist Rafael Meshuran obtained five kilograms of marijuana for biochemical research with the help of Israeli police, and then successfully isolated Δ-9THC (tetrahydrocannabinol). There are more than 130 cannabinoids in the cannabis plant, and THC is the only one that can have powerful, intoxicating psychoactive effects.

THC in cannabis plants is mainly in the form of tetrahydrocannabinol carboxylic acid (THCA), which is produced by the enzymatic condensation of geranyl pyrophosphate with 2,4-dihydroxy-6-pentylbenzoic acid Cannabidiolic acid is obtained by cyclization under the catalysis of THC acid synthase. After some time, or when heated, the THC carboxylic acid is decarboxylated to give THC. Similar to most other pharmacologically active secondary metabolites in plants, THC is a lipid found in cannabis, and the presence of THC is thought to be the plant’s (for herbivores) self-defense mechanism. Moreover, the strong absorption of THC in the UV-B segment (280-315 nanometers) may have a protective effect on plants from UV damage.

Tetrahydrocannabinol is a classic cannabinoid receptor agonist, acting through the central receptor cannabinoid receptor type 1 (Cannabinoid Receptor Type 1) CB1 and the peripheral receptor CB2. THC and its double bond isomer and its stereoisomer are one of three cannabinoids (the other two being Dimethylheptylpyran and Parahexyl) regulated by the United Nations Convention on Psychotropic Substances. It was listed in Schedule I in 1971 but was reclassified to Schedule II in 1991 following the recommendation of the World Health Organization (WHO). Based on subsequent research, the World Health Organization recommended that this reclassification be included in the less stringent Schedule III.

Once scientists managed to figure out how THC works through the endocannabinoid system, it took five years to isolate the THC-like substances we produce ourselves. This compound can be described as the human version of THC, endogenous THC, and scientists are still trying to figure out what role endogenous THC plays in the human body. Endogenous THC is like a natural correction fluid that helps you forget all the chores and let you remember the important things. Understanding some of the basic functions of endogenous THC is very helpful to explore the role of THC on the body, such as it has revealed some about the role of THC in the treatment of certain psychological diseases, such as traumatic stress disorder. The key difference between THC and endogenous THC is that THC acts longer than the endogenous THC our body produces naturally.

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