Caffeine & Neurotransmitters

Within minutes after you drink your coffee or tea, caffeine is carried by your bloodstream to all your organs and virtually every cell in your body.  Because caffeine is fat soluble, it passes easily through all cell membranes: It is quickly and completely absorbed from the stomach and intestines into the blood stream, which carries it to all the organs.  Caffeine permeates organs more rapidly than most other drugs, but not more rapidly than alcohol.  And because there are no significant physiological barriers that hinder its passage through tissue throughout the human body, the concentrations attained by caffeine are virtually the same throughout the body and in blood, saliva, and even breast milk and semen. 

Many of caffeine’s powers depend on its power to pass into the central nervous system (CNS).  To enter the CNS, caffeine must cross the blood-brain barrier, a defensive mechanism that protects the CNS from biological or chemical exposure by preventing viruses and other large (and most small) molecules from entering the brain or its surrounding fluid.  Even when injected into the bloodstream, many drugs fail to penetrate this barrier, and others enter it much less rapidly than they enter other tissues.  However, caffeine passes through the blood-brain barrier as if it did not exist.

Neurotransmitter Transmission

All psychoactive drugs, including caffeine, achieve their effects by imitating or altering the release or uptake of neurotransmitters, the chemical messengers that direct how the neurons of the CNS interact with each other.  Neurotransmitters are altered by drugs in a variety of ways, including increasing or decreasing their synthesis, inhibiting or enhancing their transport, modifying their storage, release, or the way they are degraded, or simply by directly mimicking their activity or, alternatively, by blocking their action at the receptor site.  

Neurotransmitters - Venn Diagram

Caffeine achieves many of its effects by blocking the activity of adenosine, a neurotransmitter that affects almost every bodily system.  Because one of the primary actions of adenosine is to make us tired or sleepy, caffeine, by blocking the uptake of adenosine, keeps us from feeling the effects of fatigue.  But scientists have learned that, largely as a consequence of its blockade of adenosine receptors, caffeine also has profound effects on most of the other major neurotransmitters, including dopamine, acetylcholine, serotonin, and, in high doses, on norepinephrine.  By affecting these other neurotransmitters, it is able to deliver a major boost to our capacities even when we are well-rested, something that could not be explained by the inhibition of adenosine alone.   By increasing the transmission of dopamine, caffeine improves our mood and may protect brain cells from age and disease related degeneration.  By increasing the activity of acetylcholine, caffeine increases muscular activity and may also improve long-term memory.  By raising and adjusting serotonin levels, caffeine relieves depression, makes us more relaxed, alert, and energetic, and relieves migraine headaches.

Neurotransmitters - Venn Diagram 2




The full story of caffeine’s intricate mechanism of action is still only partially understood by pharmacologists and physicians.   And though caffeine is probably the most widely studied drug in history, the effort to penetrate its mysteries continues today.  Animal studies are problematic, because rats, mice, cats, dogs, and monkeys process caffeine very differently from each other and very differently from human beings.  Human studies are sometimes bedeviled by the individual differences in the quality of responses to caffeine and differences in the rate at which it is metabolized by different people and at different times.  Finally, there is the unique problem that, because almost everyone already uses caffeine, it is difficult to determine what they would be like without it. 

            However, even if we don’t know all the answers about how caffeine works, we can classify the two major effects caffeine has on our neurotransmitters by which it achieves its magic: 

  • Caffeine alters the production or uptake of many neurotransmitters so as to increase mental and physical energy and enhance performance; and 
  • Caffeine regulates the balance of many neurotransmitters, in ways that enhance our moods, kill pain, suppress our appetite, and even protect our brain cells from damage and disease. 
Transporting Neurotransmitters


Caffeine’s Neurotransmitter Mediated Benefits

Caffeine, by acting to modifying and regulate a host of the body’s neurotransmitters, enables us to tap into our hidden potential in four major areas:


Sharpens reasoning, memory, verbal fluency, concentration, and decision-making and heightens sensuous perception. 


Enhances moods, increases relaxation, relieves boredom, boosts self-confidence.


Improves speed, endurance, energy output, strength, and reaction time, and increases thermogenesis, that is,  fat burning and metabolic rate.


Protects body cells and especially brain cells from some kinds of long-term damage and delivers many other specific therapeutic benefits including pain relief and protection from the pulmonary complications of smoking and the damage from strokes. 


12 Responses to Caffeine & Neurotransmitters

  1. dwechsler says:

    Thanks for the explanations… What I’m curious about is when I normally drink 5-7 cups of coffee a day, I go through cycles of being awake and crashing.

    Yet when I drink “bulletproof” coffee,, made with butter and coconut oil, 1-2 cups 1st thing in the morning keeps me going all day long with a high degree of alertness – I feel incredibly charged-up!

    Any idea of why? Could there be a relation between drinking oil/fat based coffee vs water-based only?

  2. romigillGill says:

    Great article. I am a bodybuilder and have been using caffeine for over 10 years (not daily) to get physical boost. I am more alert and heart rate and body tempei goes up, I have a heightened sense of smell and also more sharp.

    I am able to use 600-800mg at a time goto 3 times a day, I usually stick to 600mg before a workout or when I have to eat lots of junk food. It boosts metabolism as well.

    We build tolerance to caffeine over time. If I take 400 mg it doesn’t really help me much. After its half-life caffiene causes dehydration and I feel it in back on my neck and it causes pain until I take a nap. Also taking even 600mg caffeine causes sleepiness after eating oily food such as fries.

    I am currently experimenting on increasing Serotonin, Dopamine and endorphins to take my mind to Next Level so that I can control these with my mind rather than drugs. I am also going to use meditation to use brain capacity to help me.

    I never thought of caffeine to help with brain capacity but now I seem to have more possibilities.

    Acetylcholine-L-Carnitine, L-dopa, Omega-3, GAbA precursor, melatonin are the supplements I am using to help, with caffeine in the mix.

    Any other tips are welcome.

  3. Mark Gates says:

    I was a pot+ a day guy for 25 years. Developed A-fib due to decades of endurance training at very intense levels. I stopped drinking coffee on June 10 of 2013 and over the next few months had two heart ablations to put my heart back in sinus rhythm. The antiarrythymic drugs did not work for me. The second ablation worked, but left me with multiple PAC’S a day. I would have 200-400 daily. Had my final follow up with my cardiologist and he released me to do whatever I wanted. I had been exercising, but nothing like before and I was still on zero caffeine or almost zero.

    Last week I began drinking 2 cups of coffee a day and my PAC’s virtually stopped within 90 minutes of the first cup of coffee. Now I am having 10-20 PAC’s daily instead of hundreds. This is what led me to searching for caffeine and it’s possible effects on the heart.

    Would love to hear your thoughts on why caffeine appears to work better than the antiarrhythmic drugs for me?
    Thank you! Enjoyed the article.

    • Mark Gates says:

      If you don’t know PAC’s are premature atrial contractions. It feels like your heart is skipping.

    • It is hard for me to say specifically why caffeine has delivered the benefit of virtually stopping PAC’s. What I can say is that, although caffeine has many, many favorable effects on health and definitely extends life, the most important contribution of caffeine to health and its greatest contribution to extending life is its ability to reduce cardiovascular pathologies of all kinds. If you discover more particulars about this, please write to us again! And thank you for your contribution!

  4. Noah says:

    Thank you guys so much! I really love this website, it’s helped me so much for my schools Small Molecule Project, and I’ve learned so much trusted information. Keep the amazing work up!

  5. cacao says:

    LD50- 1000 mg according to wiki.. uncited however. (LD50= lethal dose in half of population)

  6. Alan says:

    Very good article, however as caffeine user I would love to know what is the maximum daily amount recommended. Over usage of anything has some negative issues that can develop what are they?

    • Very good question! However, there is no “maximum daily amount recommended.”

      First, people respond to different doses of caffeine differently. To give just one example, some people can drink a strong cup of coffee, containing 150mg of caffeine or more, at 11 PM and sleep well at midnight. Other people who consume even 50mg of caffeine in the morning can’t sleep at night. Who is right? Neither one is right! The fact is that, to use caffeine strategically, each person must determine, by trial and error, what caffeine does to him and use caffeine accordingly.

      Second, the amount you want to take depends on what you are trying to achieve:
      1 cup of filter drip coffee or 150mg each day ….Reduces the change of having a stroke by 25%;
      2 cups of filter drip coffee or 300mg each day….Reduces the occurrence of heart attacks by 20%;
      1 cup of filter drip coffee or 150mg each day…Reduces the occurrence of and can even partially reverse Alzheimer’s and senile dementia;
      400mg may be the best dose for most people to improve sports and exercise performance;
      100mg in the morning is enough to improve your mood for the whole day.

      Finally, the Yerkes-Dobson Effect demonstrates that using more caffeine than the dose that benefits you the most actually starts to erode the benefits, for example, in sports performance. So, you are right that using too much can be counter-productive.