Brain
Expert Pharmacologist
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Why does a person fall asleep?
Humanity has been dealing with sleep issues for a very long time, but this topic (just like any other) has not been studied to the end, although there are a number of good concepts. Pioneers in the study of sleep suggested that there is a sleep factor - a substance that accumulates during the day and causes drowsiness.
The Japanese physiologist Kuniomi Ishimori is believed to have been the first to try to isolate the sleep factor. Also among the first were René Legendre) and Henri Piéron, who induced sleep in dogs by injecting them with a substance derived from the brains of other sleep-deprived dogs.
Current scientific evidence suggests that adenosine is well suited for the role of a sleep factor. Adenosine, a ribonucleoside composed of adenine and ribose, plays a huge role in our body. It is a component of the genetic material of cells, and it is also part of the "energy" compounds of our body, such as adenosine triphosphate (ATP). It performs a number of other functions, but in the context of this article, its role as a signaling molecule with a broad physiological effect will be of interest: both in the brain and outside it. Adenosine has even been nicknamed "the signal of life" for its functions and "the body's natural defense".
Where does adenosine come from in the brain?
There are several sources of ATP:
- ATP hydrolysis
- The result of the activity of glia cells
- Others
The main supplier is ATP. The human brain consumes up to 25% of the body's energy. It gets it mainly from adenosine triphosphate. From the abbreviation you can understand the structure of the molecule: adenosine and three phosphate molecules. Energy is released in the process of ATP hydrolysis.
Some scientists compare ATP hydrolysis to gun shots. There are only three shots (three opportunities to detach phosphate molecules), and each shot releases energy, which the cells of the body use for various processes. And after three shots, as you might guess, only the adenosine molecule remains. During the day, adenosine accumulates, both intracellularly and extracellularly. Intracellular adenosine leaves the cell with the help of special transport systems.
Some scientists compare ATP hydrolysis to gun shots. There are only three shots (three opportunities to detach phosphate molecules), and each shot releases energy, which the cells of the body use for various processes. And after three shots, as you might guess, only the adenosine molecule remains. During the day, adenosine accumulates, both intracellularly and extracellularly. Intracellular adenosine leaves the cell with the help of special transport systems.
Then adenosine begins to interact with adenosine receptors. There are four types of receptors: A1, A2A, A2B, A3. They are located on neurons, as well as on the cells of other organs (heart, kidneys, etc.). All four types are grouped into the G-protein coupled receptor (GPCR) superfamily. Each of these receptors has its own ligands (substances that bind to the receptor) - agonists and antagonists.
"So, what else are these?" - you ask. Actually, it's nothing complicated. Agonists are substances that can bind to a receptor and lead to a certain effect (positive or negative). Antagonists, on the other hand, can only bind to the receptor, but they have no effect. That is, they essentially block the receptor from binding to the agonist.
So what are agonists and antagonists for adenosine receptors? Actually many substances, but we are going to look at two of them: adenosine and caffeine. The first is an agonist and the second is an adenosine receptor antagonist.
So, what effect does adenosine have by binding to the receptors? The role of adenosine in sleep induction is well studied. In fact, it induces sleepiness, albeit with some reservations, and it is a very interesting mechanism. Brain cells work long hours, a lot of adenosine accumulates, it binds to adenosine receptors, and the cells get the signal that it is time to "rest". These processes allow neurons not to overexert themselves.
"So, what else are these?" - you ask. Actually, it's nothing complicated. Agonists are substances that can bind to a receptor and lead to a certain effect (positive or negative). Antagonists, on the other hand, can only bind to the receptor, but they have no effect. That is, they essentially block the receptor from binding to the agonist.
So what are agonists and antagonists for adenosine receptors? Actually many substances, but we are going to look at two of them: adenosine and caffeine. The first is an agonist and the second is an adenosine receptor antagonist.
So, what effect does adenosine have by binding to the receptors? The role of adenosine in sleep induction is well studied. In fact, it induces sleepiness, albeit with some reservations, and it is a very interesting mechanism. Brain cells work long hours, a lot of adenosine accumulates, it binds to adenosine receptors, and the cells get the signal that it is time to "rest". These processes allow neurons not to overexert themselves.
However, if we go deeper, things are more complicated. Not all mechanisms are still understood. Interacting with different receptors, adenosine leads to different effects. Moreover, there is evidence that by interacting with the same receptor (e.g., A1A) in one region of the brain, adenosine can induce sleep, and by binding in another - wakefulness.
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What do you think coffee, tea, chocolate, energy drinks, and cocoa have in common? They all contain caffeine. Yes! After a little backstory, I'll get to it.
Caffeine is a chemical compound in the class of alkaloids. It is the most widely used psychostimulant and has a number of physiological and biochemical effects. Caffeine affects the nervous, cardiovascular, respiratory, excretory systems, and gastrointestinal tract components.
Caffeine is found in the seeds, beans and leaves of many plants (coffee, tea, cocoa, etc.). It is consumed mainly in the form of drinks (coffee, tea, energy drinks), chocolate and gum, but is also contained in toothpaste. The caffeine content of various foods has now been calculated.
Up to 99% of caffeine ingested is absorbed into the blood within 45 minutes. Plasma concentrations peak between 15 and 120 minutes after oral (mouth-to-mouth) ingestion.
How does caffeine affect the human body? Its effects depend on concentration. In moderate doses it causes such positive subjective effects as a burst of energy, increased activity, sociability and general well-being. In high doses, it can lead to a strong increase in blood pressure and other bad phenomena. What are the recommendations for caffeine intake? Up to 400 mg/day for adults, up to 300 mg/day for pregnant women, up to 2.5 mg/kg/day for children and adolescents.
Read more
What do you think coffee, tea, chocolate, energy drinks, and cocoa have in common? They all contain caffeine. Yes! After a little backstory, I'll get to it.
Caffeine is a chemical compound in the class of alkaloids. It is the most widely used psychostimulant and has a number of physiological and biochemical effects. Caffeine affects the nervous, cardiovascular, respiratory, excretory systems, and gastrointestinal tract components.
Caffeine is found in the seeds, beans and leaves of many plants (coffee, tea, cocoa, etc.). It is consumed mainly in the form of drinks (coffee, tea, energy drinks), chocolate and gum, but is also contained in toothpaste. The caffeine content of various foods has now been calculated.
Up to 99% of caffeine ingested is absorbed into the blood within 45 minutes. Plasma concentrations peak between 15 and 120 minutes after oral (mouth-to-mouth) ingestion.
How does caffeine affect the human body? Its effects depend on concentration. In moderate doses it causes such positive subjective effects as a burst of energy, increased activity, sociability and general well-being. In high doses, it can lead to a strong increase in blood pressure and other bad phenomena. What are the recommendations for caffeine intake? Up to 400 mg/day for adults, up to 300 mg/day for pregnant women, up to 2.5 mg/kg/day for children and adolescents.
Almost all the effects of caffeine are related to its role as an adenosine receptor antagonist. The fact is that caffeine has a similar structure to adenosine, so it can bind to its receptors. But it has no stimulating or inhibitory effect on the cells.
Caffeine simply blocks receptors for adenosine. The latter does not exert its effects. This point is the key to understanding the physiological action of caffeine. It does not add any energy, it simply does not allow neurons to receive a signal that it is time to take a break and rest. A person feels an incredible burst of energy at this time... But, as you might have guessed, imaginary. The whole thing lasts about 2.5-4.5 hours.
Why exactly this long? This is the so-called half-life or half-elimination time - the period of elimination of half of the substance that has entered the body. When it expires, the effects of this "refreshing drink" quickly disappear. Adenosine binds to the receptors freed from caffeine, and the person is tired and sleepy again.
As I wrote above, adenosine receptors are not only found in the brain. They are also present in the heart and kidneys. The physiological effects of caffeine on the activity of these organs may also be explained by blocking adenosine receptors.
Caffeine simply blocks receptors for adenosine. The latter does not exert its effects. This point is the key to understanding the physiological action of caffeine. It does not add any energy, it simply does not allow neurons to receive a signal that it is time to take a break and rest. A person feels an incredible burst of energy at this time... But, as you might have guessed, imaginary. The whole thing lasts about 2.5-4.5 hours.
Why exactly this long? This is the so-called half-life or half-elimination time - the period of elimination of half of the substance that has entered the body. When it expires, the effects of this "refreshing drink" quickly disappear. Adenosine binds to the receptors freed from caffeine, and the person is tired and sleepy again.
As I wrote above, adenosine receptors are not only found in the brain. They are also present in the heart and kidneys. The physiological effects of caffeine on the activity of these organs may also be explained by blocking adenosine receptors.
If adenosine interacts with receptors in the heart and kidneys, it leads to inhibition of their activity. If caffeine blocks the receptors, however, it manifests as tachycardia (increased heart rate) and polyuria (rapid urination). These effects are probably familiar to you from personal experience.
Recently, the therapeutic potential of caffeine in neurodegenerative diseases such as Alzheimer's, Parkinson's, etc., has been widely discussed in the scientific community.
Is caffeine addictive?
Based on the ISD-11 (International classification of diseases, 11th revision), yes, caffeine addiction is a mental disorder. In the DSM-5 (Diagnostic and statistical manual of mental disorders, 5th edition), caffeine use disorders are listed as a subject for further research. Also, the DSM-5 describes diagnostic patterns with nine criteria for a diagnosis of caffeine use disorder.
The three main ones are suggested below:
Recently, the therapeutic potential of caffeine in neurodegenerative diseases such as Alzheimer's, Parkinson's, etc., has been widely discussed in the scientific community.
Is caffeine addictive?
Based on the ISD-11 (International classification of diseases, 11th revision), yes, caffeine addiction is a mental disorder. In the DSM-5 (Diagnostic and statistical manual of mental disorders, 5th edition), caffeine use disorders are listed as a subject for further research. Also, the DSM-5 describes diagnostic patterns with nine criteria for a diagnosis of caffeine use disorder.
The three main ones are suggested below:
- Constant and unsuccessful attempts to reduce and control caffeine intake.
- Continued use of caffeine despite knowledge of a physical or psychological problem.
- Withdrawal syndrome or use of caffeine to get rid of the syndrome.
It is important to note that caffeine addiction does not occur in all people. For its development certain conditions (high doses of caffeine, simultaneous consumption of different caffeine-containing products, etc.) are necessary.
What is withdrawal syndrome? The WHO gives the following definition: it is a group of symptoms of varying clustering and severity that occur when a psychoactive substance that has been taken repeatedly, usually over a long period and/or in high doses, is discontinued or reduced. That is, in essence, "withdrawal." So, when a person goes several hours (from 12 hours) without caffeine, he begins to experience these symptoms:
What is withdrawal syndrome? The WHO gives the following definition: it is a group of symptoms of varying clustering and severity that occur when a psychoactive substance that has been taken repeatedly, usually over a long period and/or in high doses, is discontinued or reduced. That is, in essence, "withdrawal." So, when a person goes several hours (from 12 hours) without caffeine, he begins to experience these symptoms:
- Headache;
- Fatigue;
- Decreased vigor;
- Decreased attentiveness;
- Sleepiness;
- Irritability;
- Concentration problems;
- Depressed mood.
Caffeine is often referred to as a drug on the Internet, but there is no scientific consensus on this issue. But it is safe to say that caffeine does not have the same effect on a person's social life as opiates and LSD.
Are tolerance and addiction the same thing?
It is necessary to distinguish between these two concepts. If dependence means the body's need for caffeine, then tolerance means the body's immunity to caffeine. What does this mean? It means that caffeine, for a number of reasons, does not exhibit its physiological effects.
So how is caffeine tolerance formed? There are a number of concepts of its formation. A striking example is the concept of increasing the number of adenosine receptors in response to prolonged ingestion of large doses of caffeine. How does all this happen? See the figure below.
I will take as a basis one of the main sources of caffeine - coffee. Caffeine tolerance is characteristic of individuals who consume coffee in large quantities and on a regular basis. This usually occurs in the morning or between work/study hours. People drink it for a variety of reasons: it helps them wake up, it smells good, it gives them energy, or they want to feel part of the megapolis crowd (in short, it's fashionable).
It is necessary to distinguish between these two concepts. If dependence means the body's need for caffeine, then tolerance means the body's immunity to caffeine. What does this mean? It means that caffeine, for a number of reasons, does not exhibit its physiological effects.
So how is caffeine tolerance formed? There are a number of concepts of its formation. A striking example is the concept of increasing the number of adenosine receptors in response to prolonged ingestion of large doses of caffeine. How does all this happen? See the figure below.
I will take as a basis one of the main sources of caffeine - coffee. Caffeine tolerance is characteristic of individuals who consume coffee in large quantities and on a regular basis. This usually occurs in the morning or between work/study hours. People drink it for a variety of reasons: it helps them wake up, it smells good, it gives them energy, or they want to feel part of the megapolis crowd (in short, it's fashionable).
Well, in general, after drinking coffee, a person feels just like a "king of the mountain". You don't want to sleep, your heart starts beating more often, you feel an incredible burst of energy, and sometimes you even want to go to the restroom. The mechanism here is the same: blocking adenosine receptors.
The fact is that with chronic caffeine use, adenosine can't attach to its receptors. The body sees that there is a lot of adenosine, which means it has nowhere to cling - not enough receptors! In response, new adenosine receptors are synthesized in the brain. Adenosine successfully interacts with them, and the person begins to feel drowsy, tired, although he continues to drink coffee in relatively large quantities.
So, one regular dose of caffeine is no longer enough. The person starts to drink more. And it goes the same way. At first it will help, but then it won't (new receptors are formed again). I hope you get the point.
Conclusion
Caffeine is the most widely used psychostimulant substance, which has both positive and negative effects on our bodies, so it is worth taking it rationally. So when you once again have a burning deadline, before drinking a couple of cups of coffee or energy drinks, think about whether it is better to sleep? If you drink several cups of coffee a day, I hope this article will be the impetus for you to create a new healthy habit (reduce your caffeine intake)!
To better understand and reinforce this information, I highly suggest rereading this article again, going to the literature cited, watching the YouTube videos (like THIS one ), or printing out my poster.
The fact is that with chronic caffeine use, adenosine can't attach to its receptors. The body sees that there is a lot of adenosine, which means it has nowhere to cling - not enough receptors! In response, new adenosine receptors are synthesized in the brain. Adenosine successfully interacts with them, and the person begins to feel drowsy, tired, although he continues to drink coffee in relatively large quantities.
So, one regular dose of caffeine is no longer enough. The person starts to drink more. And it goes the same way. At first it will help, but then it won't (new receptors are formed again). I hope you get the point.
Conclusion
Caffeine is the most widely used psychostimulant substance, which has both positive and negative effects on our bodies, so it is worth taking it rationally. So when you once again have a burning deadline, before drinking a couple of cups of coffee or energy drinks, think about whether it is better to sleep? If you drink several cups of coffee a day, I hope this article will be the impetus for you to create a new healthy habit (reduce your caffeine intake)!
To better understand and reinforce this information, I highly suggest rereading this article again, going to the literature cited, watching the YouTube videos (like THIS one ), or printing out my poster.