Thc receptors brain

How THC Binds to Cannabinoid Receptors in the Brain

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Seconds after marijuana is consumed it begins to affect your brain. The main cannabinoid produced by the cannabis plant is called THC (tetrahydrocannabinol), this cannabinoid binds to cannabinoid receptors within three main places in the brain. The cerebellum, basal ganglia, and hippocampus are responsible for short-term memory, learning, problem-solving, and coordination. Cannabinoid receptors are activated by anandamide, which is a neurotransmitter and natural cannabinoid that the body produces. THC mimics anandamide and binds to the cannabinoid receptors that activate neurons in the brain affecting the mind and body. For more brain health research, visit Brain Reference.

To understand the steps that THC take to bind and active neurons, it's best to know the parts of the brain that are involved, "Neurons are the cells that process information in the brain. Chemicals called neurotransmitters allow neurons to communicate with each other. Neurotransmitters fill the gap, or synapse, between two neurons and bind to protein receptors, which allow various functions in the brain and body to be turned on and off. Some neurons have thousands of receptors that are specific to particular neurotransmitters. Foreign chemicals, like THC, can mimic or block actions of neurotransmitters and interfere with normal functions." Consuming THC may also harm one's teeth and gums but individuals have been using supplements such as Steel Bite Pro to help.

Cannabinoids work slightly different from other neurotransmitters; in fact, they work backwards. Neurons work by communicating with each other and the rest of the body by sending chemical messages. These messages are responsible for regulating our motor and cognitive functions. "Typically, the chemicals (called neurotransmitters) are released from a neuron (a presynaptic cell), travel across a small gap (the synapse), and then attach to specific receptors located on a nearby neuron (postsynaptic cell). " When this occurs, it sends the receiving neuron into action, allowing the message to travel further throughout the body. However, with the endocannabinoid (EC) system, the message is communicated differently. "When the postsynaptic neuron is activated, cannabinoids (chemical messengers of the EC system) are made on demand from lipid precursors (fat cells) already present in the neuron." Once they are released from that cell, they travel backwards to the presynaptic neuron, allowing them to attach to cannabinoid receptors. They can control what happens next when the cells are activated, allowing it to control how messages are sent, received, and processed but the cell.

Scientists have identified the two primary cannabinoid receptors which are CB1 and CB2. The CB1 receptor is found in the brain and nervous system and is the main receptor for THC and anandamide. The receptor found in the immune system and surrounding structures is CB2, which is responsible for modulating antiinflammatory effects. When "THC gets into the brain rapidly it attaches to cannabinoid receptors. The natural EC system is finely tuned to react appropriately to incoming information. But THC overwhelms the EC system. It prevents the natural chemicals from doing their job properly and throws the whole system off balance." This is why scientists have found THC to affect so many systems throughout the body from motor skills to cognitive function. As such strangely some even think THC is a great way to manage some pest control issue too.

The following video does a great job of explaining how the brain normally functions without any interference from THC and how it changes once THC in consumed.

Sources: HowStuffWorks, Scholastic, Leafly, Ministry of Hemp

About the Author

Amanda Kahl

Amanda has a Bachelor's in Biological Sciences from the University of Cincinnati. She has a passion for animals, conservation, and environmental sciences. Through her career in science and research, she is able to develop her passion and hopes to pass on to others the joy of learning about science.

Cannabinoid receptors: where they are and what they do

Review

. 2008 May;20 Suppl 1:10-4.

doi: 10.1111/j.1365-2826.2008.01671.x.

K Mackie¹

Affiliations

Affiliation

¹ Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47401, USA. [email protected]

PMID: 18426493
DOI: 10.1111/j.1365-2826.2008.01671.x

Review

K Mackie. J Neuroendocrinol. 2008 May.

. 2008 May;20 Suppl 1:10-4.

doi: 10. 1111/j.1365-2826.2008.01671.x.

Author

K Mackie¹

Affiliation

¹ Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47401, USA. [email protected]

PMID: 18426493
DOI: 10.1111/j.1365-2826.2008.01671.x

Abstract

The endocannabinoid system consists of the endogenous cannabinoids (endocannabinoids), cannabinoid receptors and the enzymes that synthesise and degrade endocannabinoids. Many of the effects of cannabinoids and endocannabinoids are mediated by two G protein-coupled receptors (GPCRs), CB(1) and CB(2), although additional receptors may be involved. CB(1) receptors are present in very high levels in several brain regions and in lower amounts in a more widespread fashion. These receptors mediate many of the psychoactive effects of cannabinoids. CB(2) receptors have a more restricted distribution, being found in a number of immune cells and in a few neurones. Both CB(1) and CB(2) couple primarily to inhibitory G proteins and are subject to the same pharmacological influences as other GPCRs. Thus, partial agonism, functional selectivity and inverse agonism all play important roles in determining the cellular response to specific cannabinoid receptor ligands.

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What Science Knows About the Effects of Marijuana on the Brain - Neuroscientist Explains

Health

Is it true that regular use of marijuana worsens memory and how cannabinoids fight cancer cells? Angelina Lesnikova, a neuroscientist and PhD student at the University of Helsinki, answered these questions during the lecture "Drug Talks" organized by the St. Petersburg educational project "Grass".

1. There are a lot of cannabinoid receptors in our body

Paradoxically, cannabinoid receptors are the most numerous in the central nervous system. What is it and why are they called that? When a receptor is studied in science, one of the key ways to describe it is to designate what molecule causes its activation. For example, there are nicotinic receptors. This does not mean that they are specifically designed for the perception of nicotine. But due to the fact that they were first described as receptors that are activated with the help of this substance, they began to be called nicotinic. The same is true for cannabinoids. They are present in our brain, lungs, gastrointestinal tract, muscles and respond to cannabinoids.

2. The human brain itself produces endocannabinoids

The human body contains endocannabinoids. These substances are naturally produced by the brain and are used as neurotransmitters. Endocannabinoids are structurally similar to phytocannabinoids (which are found in marijuana), have similar effects, and activate the same receptors. They are involved in the suppression of pain sensations, the occurrence of a feeling of euphoria, and also participate in the regulation of appetite, affect memory and learning.

3. Regular use of marijuana reduces the number of cannabinoid receptors in the brain

Regular use of marijuana reduces the number of cannabinoid receptors in the brain, scientists found during the study. It was attended by people who regularly smoked marijuana. And as a control group, those who did not use it were involved. And when measuring the number of receptors in the cerebral cortex, the first group turned out to have more of them than the second. The fact is that when there are too many cannabinoids in the body, it understands that something is wrong here. The receptors have too much load, they are too active, and this causes unnatural physiological processes in the body. And in order to reduce this effect, in order to protect itself from over-activation of these receptors, the body itself reduces their activity. Therefore, when a person smokes a lot and regularly, the number of these receptors decreases. This is due to the emergence of tolerance in smokers.

4. Smoking marijuana clearly has an effect on memory, but scientists have not yet realized how bad it is

Evidence for the long-term effects of cannabis use on memory differs. It is believed that irregular use does not cause long-term memory impairment. With regular use, according to some sources, the normal functioning of the memory returns after 48 hours - 1 month after quitting, according to others, the normal functioning of the memory is not restored even after 1 year of smoking cessation. Why can this happen at all? Scientists believe that memory impairment is associated with the suppression of the work of mitochondria - the energy centers of cells, on the membrane of which also contains cannabinoid receptors.

5. Regular use of cannabinoids can reduce the production of dopamine

Dopamine is a hormone of pleasure, which also has one of the most important functions - motivating. That is, when you have the motivation to do something, it means that your brain cells have released this neurotransmitter. A study published in the journal Molecular Psychiatry showed that with regular use of cannabis, the human brain begins to produce less of it. Accordingly, with a decrease in the amount of dopamine, a number of physiological and psychological disorders can occur.

6. Marijuana may help treat Alzheimer's disease

THC (tetrahydrocannabinol, one of the main cannabinoids) may be a potential cure for Alzheimer's disease. It develops in older people. The main marker of the disease is a decrease in the amount of gray matter in the brain, a large number of neurons die off.

If you look at the brain of a patient with this disease, you can see accumulations of protein. This protein changes its shape and rolls into balls. The tangles join together and plaques form. Neurons because of this "suffocate". This is called neurofibrillary tangles and amyloid plaques.
So THC is able to attach to amyloid proteins and prevent the formation of plaques. It prevents the protein from taking on an irregular shape. The mechanism has been studied in animals, and the study is published on the US National Center for Biotechnology Information website.

7. Cannabinoids can inhibit the development of cancer cells

Cannabinoids were originally used to relieve the side effects of chemotherapy in cancer patients. A person who undergoes chemotherapy has a large number of physiological disorders. For example, he is constantly nauseous. Cannabinoids facilitated the human condition and had an analgesic effect. But in the end, scientists found that cannabinoids can reduce tumors and destroy cancer cells, while not causing the destruction of healthy cells.

We remind you that Russia has a law “On Narcotic Drugs and Psychotropic Substances”. The use of narcotic substances based on marijuana is an administrative offense punishable by a fine.

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Author:

Katerina Reznikova, April 25, 2018

Cannabinoids in medicine: a dead end or a promising direction?

Cannabis is surrounded by a "drug" halo, and the discussion of this plant from the standpoint of medicine is often perceived only as an excuse to talk about the legalization of marijuana. The text you are reading is not related to the discussion on this topic. We will talk about what this plant can give to medicine.

This text "grew" from the author's speech at the lecture hall "Psychiatry and Evidence-Based Medicine" of the Medach community. The recording of the lecture stream, which was performed by Future Biotech, is available on YouTube.

Plants for ropes

The natural source of cannabinoids is hemp ( Cannabis sativa ) (Fig. 1) — a dioecious plant, which has separate individuals with male and female flowers. Hemp is unpretentious enough to be grown on an industrial scale.

Picture 1. Hemp seed.

medieval botanical atlas

Hemp has long been a source of material for fabrics and ropes: the famous hemp ropes were made from hemp fibers. Also, different parts of cannabis were used as cosmetics and fed to livestock. The psychotropic effect of cannabis was also known to people, but in this capacity it was used relatively rarely.

The industrial use of cannabis was seriously restricted in 1961 due to the entry into force of the "Single Convention on Narcotic Drugs". Despite this fact and the fact that laws have been passed in many countries prohibiting the use of cannabis derivatives, today between 130 and 230 million people worldwide use it as a drug as a drug [1].

The psychological effects of cannabis are caused by cannabinoids, a group of plant-derived terpenephenolic compounds. In total, several dozen cannabinoids are known, but Δ 9 has the strongest psychotropic effect.0074 9 -tetrahydrocannabinol (THC) (Fig. 2). Other members of this family have it to a lesser extent. In plants, cannabinoids are formed in two ways (Fig. 3). The polyketide pathway allows the synthesis of cannabinoids from olivetolic acid. The second mechanism is more complex: it is based on the production of geranyl diphosphate and the subsequent synthesis of monoterpenes [2].

Figure 2. Tetrahydrocannabinol molecule.

Wikipedia

Figure 3. Cannabinoid biosynthesis pathways in cannabis sativa. To see the picture in full size, click on it.

I wonder why hemp needs this group of substances at all? Most likely, as in the case of nicotine, cannabinoids protect the plant from insect pests. It is not entirely clear whether they have a direct effect on the central nervous system of insects or act in some other way, but their effectiveness in this role is not disputed.

In search of a receptor

The possibility of a chemical substance affecting the human body implies the presence of an application point (in other words, action targets ). It could be a specific receptor, as is the case with digitalis digoxin. Another option is the global effect of the drug on a variety of processes and binding to multiple receptors. Alcohol has a similar effect (but this is not accurate) [3].

Scientists have long tried to find the target of cannabinoids in the human body. This was done in 1988, when cannabinoid type 1 receptors (CB ₁ receptors) were described [4]. At 19In 1993, the second class of cannabinoid receptors (CB ₂ receptors) was also discovered [5]. CB ₁ receptors are located in the central nervous system. Activation and blocking of CB ₁ affect memory processes, neuroprotection, and nociception. In addition to the brain, they can be found in the liver, myocardium, kidneys, gastrointestinal tract, lungs, as well as in the endothelial lining and muscular wall of blood vessels. CB ₂ are widely represented on immune and endothelial cells (Fig. 4) [6]. Synthetic cannabinoids found in smoking mixtures mainly stimulate CB ₁ receptors - that is why these drugs so seriously change the mental state of a person [7].

Figure 4. Expression of cannabinoid receptors in human organs.

CB ₁ - and CB ₂ receptors coincide by 44% in their amino acid sequence [8]. Both types of receptors belong to the class of G-protein-coupled receptors (on our website you can read a selection of articles about this type of cell structures). Now scientists know with high accuracy the crystal structure of the cannabinoid receptor [9]. In addition, in recent years, it has been possible to understand how receptors change when interacting with THC and another cannabinoid, hexahydrocannabinol [10]. Interestingly, with the help of pharmacological methods, it is possible to separately block CB ₁ - and CB ₂ receptors, but it is not yet possible to stimulate them separately.

The question arises: why do we need cannabis receptors in our body? A year before the description of the second type of receptor, the journal Science published a paper describing anandamide, a representative of the endocannabinoid system of our body [11]. In other words, it is a molecule produced in the human body that acts on the same receptors as cannabinoids. In addition to it, 2-arachidonoylglycerol belongs to endogenous cannabinoids. CB₁ - receptors are located in the neurons of the cerebral cortex, basal ganglia, cerebellum and hippocampus. The function of these receptors is to reduce the release of neurotransmitters — GABA or glutamate (Fig. 5) [12–14].

Figure 5. The role of CB receptors ₁ in the nervous system. Stimulation of postsynaptic receptors leads to the production of 2-arachnoidylglycerol (2-AG), which, by binding to the presynaptic receptor, reduces the production of neurotransmitters by a feedback mechanism. In addition, 2-arachidonoylglycerol reduces the production of ATP in astrocyte mitochondria, reducing the intensity of metabolic processes. Legend: mGluR5 — type 5 metabotropic glutamate receptor; M1 - muscarinic receptor; CB1 - CB ₁ - receptor; MAGL - monoacylglycerol lipase; NAPE-PLD - N-arachnoidylphosphatidylethanolamine phospholipase D; ATP - ATP; 2-AG - 2-arachnoidylglycerol; AA - anandamide; ABHD6 — protein 6 containing α/β-hydrolase domain; PIP ₂ - phosphatidylinositol bisphosphate; DAGLα - diacylglycerol lipase α; PLCβ — phospholipase C β; COX-2 - cyclooxygenase-2; FAAH - fatty acid amide hydrolase; PGE2-GE - glycerol ester of prostaglandin E2. To see the picture in full size, click on it.

Cannabis in a white coat

Despite the limitations in use, marijuana itself and isolated active substances of cannabis began to be used in medicine. The cultivation of cannabis for medical purposes and the subsequent production of medicines from it are strictly regulated by the state. It is unlikely that such activities of scientists can be considered as an argument in favor of the legalization of marijuana or its safety for humans. When it comes to cannabis and its medical uses, another example of a "natural" drug that comes to mind is penicillin. The invention of penicillin was due to the fact that a certain type of mold inhibited the growth of bacteria in the laboratory. Nobel laureate Alexander Fleming, who made this discovery, later planned to isolate the active substance, synthesize it on an industrial scale and use it as a medicine [15].

With cannabis and cannabinoids, the situation is similar: why force people to smoke marijuana when you can simply identify the active substance, synthesize or isolate it from plants and use it in the treatment of diseases? The medical use of cannabinoids is reminiscent of how artemisinin from the annual mugwort was first used to treat malaria. Chinese researcher Yuyu Tu received the Nobel Prize in Physiology and Medicine in 2015 for this discovery [16].

Thanks to the song "In the Supermarket" by the group "Casta", we know that under the influence of cannabinoids, a person's appetite increases. Why and how this happens is discussed in detail in the article “ has hit " [17], and we won't dwell on that here. Now it is important to understand under what conditions this effect of cannabinoids can be used. As a rule, we are talking about the depletion of the body, which is observed in the advanced stages of HIV infection. In a 2013 meta-analysis, it was found that the use of THC and the use of marijuana itself can increase the appetite of patients in this group and contribute to weight gain [18]. An earlier study compared dronabinol (a synthetic analogue of THC) with megestrol acetate in terms of weight gain in cancer-wasting patients [19]. It turned out that megestrol acetate copes with this task better than its competitor.

Another use of cannabinoids is the treatment of nausea and vomiting in cancer chemotherapy [20]. The area of the brain responsible for the occurrence of vomiting ( area postrema ) is rich in type 1 cannabinoid receptors. The same receptors are present in large numbers in the nucleus of the solitary tract and nuclei of the vagus nerve, which are also involved in the processes of nausea and vomiting. Stimulation of cannabinoid receptors on these nerve structures leads to a decrease in the feeling of nausea and the cessation of vomiting. Studies have shown that cannabinoids cope better with chemotherapy-induced nausea and vomiting than antipsychotics, but lose in this regard to ondansetron. Typically, cannabinoids are not first-line drugs and are used when other treatments have failed.

Interestingly, cannabinoids also have potential as anti-cancer drugs [21]. A large amount of laboratory data has been accumulated that the stimulation of cannabinoid receptors can lead to the death of cancer cells. Similar studies have been conducted on breast, prostate, lung, and pancreatic cancers. These types of tumors are widespread in the population and give high mortality rates, and existing treatments often do not give a satisfactory result. If we can find a way to stimulate the cannabinoid receptors of cancer cells and not activate the receptors in the CNS, then we will have a good cancer treatment in our hands.

The problem is similar to the one that confronted researchers when they were looking for the "ideal" opioid, a substance with powerful analgesic effects, but without the side effects of addiction and respiratory depression. Apparently, after a long search, this problem was solved [22]. It is now possible to use technology to digitally design new molecules to find the "ideal" cannabinoid that will only work on cancer cells.

Another approach is related to the characteristics of cannabinoid receptors - they cannot be stimulated individually, but they can be blocked. In this case, the drug will be a mixture of a non-selective cannabinoid receptor stimulant and their selective blocker. A similar principle is used in the treatment of Parkinson's disease with a combination of levodopa and carbidopa. Levodopa as a precursor of dopamine enters the central nervous system and improves the patient's motor function. Carbidopa "works" on the periphery, preventing the side effects of levodopa from manifesting itself.

In addition to being used in oncopathology and AIDS, cannabinoids can be used in the treatment of multiple sclerosis [23]. They are better than placebo in managing spasticity in this disease (but the difference is not very large). In addition to this, cannabinoids help in the fight against neuropathic pain of various origins, which adds points to them (Fig. 6) [24].

Figure 6. Sativex is a cannabinoid-based drug that helps fight spasms and pain in multiple sclerosis.

volteface.me

Source of noise

Now let's talk about how cannabinoids and schizophrenia are related. Schizophrenia is a chronic mental disorder characterized by three groups of symptoms. The first group (productive symptoms) includes delusions and hallucinations. The second group included negative symptoms: volitional decline, smoothness of emotional reactions. The third group (cognitive symptoms) are specific distortions in the processing of information by the patient's brain. You can read more about schizophrenia in the article " The Disease of Lost Connections " on our website [25].

The feeling of being watched, the constant internal tension and suspicion that a person experiences is a phenomenon often found in schizophrenia. For simplicity, it can be called paranoia. As the aforementioned Casta group informs us, when using marijuana, there can be a feeling of being watched. Under the influence of cannabinoids, a person may feel that people around him are looking at him, discussing him, or laughing at him. Experiencing such sensations, a person begins to be afraid and avoid crowded places, tries to behave secretly.

This similarity suggests that cannabinoids can change the brain of a healthy person so that it becomes similar to the brain of a patient with schizophrenia. Our neurons are constantly exchanging electrical signals, and in a healthy person this process is stable and without significant failures. In the case of schizophrenia, the signals become less stable, the amount of neural noise in them increases. The more noise, the higher the random component in the signal, the less stable the connection between neurons. This phenomenon is observed in schizophrenia, and it explains part of the symptoms of the disease. At the same time, an increased level of neuronal noise is observed in the period without pronounced productive symptoms [26]. The level of neuronal noise becomes significantly higher during the period of exacerbation of the disease [27].

Read the article " Chaos in the brain " about how stochastic processes in the brain are arranged in general [28].

When using cannabinoids, healthy participants in the experiment showed an increase in the level of neuronal noise, and at the same time they experienced a number of symptoms characteristic of schizophrenia [29]. It is possible that the increase in the level of neuronal noise is caused by a malfunction of GABAergic interneurons, which stabilize the signal under normal conditions. Stimulation of this population of nerve cells with cannabinoids disrupts their function, and the signal becomes more chaotic. However, if we can find a cannabinoid that can do the opposite (that is, improve the functioning of interneurons), then we can get another cure for schizophrenia.

Cannabinoids, despite their "narcotic" tail, are just one of many classes of chemical compounds. They can be used for medical purposes, and this is already happening. The range of their application today is not very wide, but it can be increased through further research. Will we get a new cannabis medicine? The question remains open. Open and interesting.

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Spice smoking blends - not without "chemistry";
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Multiple sclerosis: immune system versus brain;
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Thc receptors brain

How THC Binds to Cannabinoid Receptors in the Brain

Cannabinoid receptors: where they are and what they do

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Author

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Abstract

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What Science Knows About the Effects of Marijuana on the Brain - Neuroscientist Explains

1. There are a lot of cannabinoid receptors in our body

2. The human brain itself produces endocannabinoids

3. Regular use of marijuana reduces the number of cannabinoid receptors in the brain

4. Smoking marijuana clearly has an effect on memory, but scientists have not yet realized how bad it is

5. Regular use of cannabinoids can reduce the production of dopamine

6. Marijuana may help treat Alzheimer's disease

7. Cannabinoids can inhibit the development of cancer cells

Cannabinoids in medicine: a dead end or a promising direction?

Plants for ropes

In search of a receptor

Cannabis in a white coat

Source of noise