How Caffeine Affects Neurotransmitters and Profoundly Changes Your Brain

By on July 23, 2014

caffeineOn this blog I have written a fair bit already about nootropics: substances you can use to potentially sharpen your mind. It’s a fascinating topic, although I’ve yet to find anything that I’d recommend using on a regular basis. My research continues…

But there is one nootropic I’m already using a lot and the same probably goes for you. It’s a highly potent neuroactive compound that most of us consume in great quantities everyday – and in most cases we don’t give much thought as to how it works.

Okay so the suspense is ruined a little by the title of this post… I’m talking about caffeine – a substance that many of us use to wake up in the morning and/or to get through heavy workloads. We also tend to drink it socially and in general a lot of people are addicted to it.

But is it good for us? And could we be getting more from it if we knew a little more about how it worked? Below I’m going to examine precisely how caffeine affects the various neurotransmitters in the brain in order to cause the effects it does. From there you can draw your own conclusions, but you might be surprised at just how profound the change is. For a grounding in what neurotransmitters are, try reading this guide to the brain first.

Neurotransmitters Affected by Caffeine

Adenosine: Adenosine is the main neurotransmitter affected by caffeine and this is the mechanism through which all the other effects occur.

Adenosine is a substance (a ‘purine nucleoside) that is produced in the brain as our neurons fire. Over time more and more accumulates and has the effect of suppressing arousal and reducing the amount of firing. In other words, it accumulates throughout the day and slows us down to the point where we feel ready for bed.

What caffeine does is to block the adenosine receptors (specifically the A1 receptors making it an A1 antagonist) by mimicking adenosine, thus preventing them from detecting the real stuff. In other words, caffeine renders the adenosine inert, making us feel more awake and alert as a result. So adenosine is the break that slows down our brain’s horsepower, and caffeine dampens those breaks. This is how it helps to combat tiredness and brain fog.

Glutamate: When you block the A1 receptors, this results in the neurons throughout the brain firing much more regularly and rapidly. To the brain this suggests something important is going on, so it responds by releasing more neurotransmitters – specifically stimulants that are involved in attention and learning.

Glutamate is one such ‘excitatory’ neurotransmitter which has an important role in ‘long-term potentiation’. What this means, is that glutamate increases the strength of the connection between neurons that fire at the same time. This then means that if one of those neurons fires independenty, it is more likely to trigger the other one. This way glutamate, and so caffeine, can aid learning and at the same time even increase brain plasticity.

Dopamine: Dopamine we often know as the ‘reward chemical’ in the brain, but it’s important to understand that this isn’t a straightforwardly accurate description. Dopamine is released when we do something ‘good’ yes, and this way our actions are reinforced such that we are likely to repeat them again. However dopamine is not what creates the feeling of enjoyment for that stimulus, it just helps to cement the connection. At the same time, dopamine can also be released during a ‘near miss’ such that it also reinforces ‘nearly useful’ behaviours and is also involved in the ‘anticipation’ of reward. So it’s complex. This all takes place in the ‘mesolimbic pathway’ also known as the ‘reward pathway’ where dopamine acts on the D2 receptors.

Having fewer D2 receptors in the thalamus meanwhile is associated with an increased chance of being a ‘creative genius’ as well as an increased chance of being schizophrenic. The thalamus, among other things, is responsible for ‘filtering’ thoughts and ideas that make it to the cortex for higher reasoning. With fewer D2 receptors, there may be less signal ‘filtering’ occurring resulting in more unusual connections being formed and more ‘out the box thinking’. Unfortunately a lack of D2 receptors in the thalamus is also correlated with an increased chance of someone being schizophrenic… Here’s an interesting study if you want to learn more. Whether this means that caffeine could blunt creativity is uncertain, but there are those who think it’s possible. Check out this article on the New Yorker which makes that conclusion.

At the same time dopamine also regulates motor control, attention and even the production of breast milk!

Epinephrine (Adrenaline): Now your brain is lighting up like a Christmas tree which tells your body that something really important must be going on. Normally you wouldn’t be this alert and focused unless you were being chased by a lion, and thus the adrenal glands kick in in order to release adrenaline. Adrenaline is the hormone that creates the ‘fight or flight’ response. It speeds up our metabolism and our heartrate, it directs blood flow away from ‘unnecessary’ processes like digestion and it actually increases physical strength. It’s also what can lead to caffeine making us jittery and anxious and it makes it very hard for us to get to sleep.

Cortisol: Cortisol is the ‘stress hormone’ and this can increase alongside adrenaline when you take in caffeine. Cortisol can make you feel anxious, but it can also stimulate the release of insulin, thus resulting in your blood sugar getting used up and stored as fat while also making you hungry for snacks. If you’re dieting then, caffeine might actually contribute to snacking and lipogenesis. Many people start their day with caffeine, which is possibly a mistake as this is when we have the most cortisol in our system already.

Serotonin: Serotonin is often called the ‘feel good hormone’ and is used to regulate the mood (as well as to aid in memory, sleep and various other functions). When caffeine increases the amount of cortisol, serotonin levels increase too to try and counterbalance this. This is important to consider when thinking about brain chemistry – nothing occurs in a vacuum and altering any one neutransmitter is almost bound to affect countless others.

Caffeine Tolerance and Withdrawal

When you elevate levels of anything in the brain artificially, the brain tends to react by changing its composition permanently in order to account for that. This way we can build up a ‘tolerance’ for caffeine meaning we need more in order to achieve the same effect we previously experienced, and we might suffer with withdrawal symptoms when attempting to cut back.

How this tolerance comes about is a topic that’s debated. It may be that the brain creates more adenosine receptors, or that they become a little less susceptible to caffeine.

Meanwhile though, living with elevated levels of the various neurotransmitters described above could also lead to other changes in the brain.  Studies show that drinking caffeine over a long time can decrease your norepinephrine and epinephrine receptors, as well as your serotonin and dopamine receptors. All this could suggest that the brain would be less ‘on’ without the presence of caffeine to give it that boost – unless you go cold turkey for a while (causing headaches, nausea and possible depression for a week or two).

And the reason that first cup of coffee feels so good in the morning may even be to do with the fact that you were experiencing withdrawal. Cutting back on caffeine might just be the better long term solution for brain fog.

The average ‘half-life’ of caffeine is six hours meaning it wears off after that time. If you’re on the pill or if you’re menstruating, then this can take up to twice as long. And if you’re a smoker then the nicotine will cut it in half so it will wear off after three hours (why many smokers are also caffeine addicts among other reasons). As you can imagine, it’s common to experience something of a ‘crash’ at this point once the A1 receptors open up again and that adenosine comes rushing in just when your body is exhausted from being in a state of hyper-arousal.

What to do With This Information

So that’s how caffeine works on the brain. It can aid learning and brain plasticity, but in the long term it might actually make you sluggish. It can also lead to several ‘peaks and troughs’ and may encourage weight gain – even though it increases your metabolism.

I don’t like it either – I love coffee and tea. So what’s the answer?

That’s up to you, I’m just providing the information. I can though tell you what I’m going to do which is to a) cut back a little and b) avoid having caffeine in the latter half of the day so that my brain can actually recover properly during the night.

I’m only going that far because I really like caffeine and to be honest, I feel pretty fine as I am. I did try cutting back on caffeine once before, and I might do that experiment again sometime now I’m older and wiser, but I have other things on my mind at the moment.

And if I were to use caffeine strictly as a nootropic, I’d probably go about it by quitting for a bit to get rid of my tolerance, then drinking a large amount only when trying to learn new things in order to take advantage of the effects it has on learning, attention and association. If you try that, let me know how it works out for you!

In the interests of full-disclosure, I am literally drinking a massive latte right now…

About Adam Sinicki

Adam Sinicki, AKA The Bioneer, is a writer, personal trainer, author, entrepreneur, and web developer. I've been writing about health, psychology, and fitness for the past 10+ years and have a fascination with the limits of human performance. When I'm not running my online businesses or training, I love sandwiches, computer games, comics, and hanging out with my family.


  1. Jake Hayes says:

    Well I’m fucked I drank a Mountain Dew at 6:30 PM. Wish me luck.

  2. Maria says:

    Caffeine nearly killed me. It’s a very strong drug. They put me on beta blockers for tachycardia and were about to do an ablation thinking I had a second pacemaker. My husband said “no way! Try getting off the caffeine first, see what happens”…what??? I have been drinking caffeine my entire life! I’m Latina, it’s my birthright!!! Well, it turns out he was right. Went through a massive headache ???? for a few days but emerged feeling cleaned and calm and happy. It’s been 8 years and I’ve never looked back. ADIÓS café con leche ????!!! #caffeineholics anonymous #

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