Coffee is the second most traded resource in the world, mainly because a large share of the population is addicted to caffeine. In the Western world, over 75% of adults drink caffeine-containing beverages daily.
When caffeine was introduced to the Western world, a lot of people started consuming it widely. Some historians argue that caffeine contributed significantly to the speed and extent of the scientific revolution, in part because people switched from drinking beer/ale in the morning (yes, they really did that in Europe) to drinking coffee, with significant societal impacts.
Caffeine has been in widespread use for over 200 years, and it was the only stimulant widely available until the 20th century. This makes caffeine also one of the most widely researched exogenous molecules overall. Consequently, we have truckloads of data showing that caffeine is quite safe for life-long consumption.
When it comes to mind-altering substances, caffeine is an outlier. Its use is socially acceptable almost everywhere in the world (except for Mormons). Most people do not consider caffeine a “drug” in the same way that ethanol is socially acceptable and not considered a “drug” – though mammalian physiology could not care less about our arbitrary social acceptance.
Personal experience
As James Beshara puts it in his book Beyond Coffee: “80 percent of the world consumes caffeine each day to wake them up and give them a boost for their daily tasks. Whether it’s black tea or coffee, most of us consume the same ingredients we consumed 200 years ago without realizing coffee beans and tea leaves are not the only sources of energy that nature provides us.” That was me a couple of years ago.
In my early twenties, I used to be a caffeine addict consuming about 300-500mg of caffeine daily. As I went to Uganda to work in a refugee camp, I was forcibly put through a horrific withdrawal. While the first few days were harsh (headache, apathy, “meh”-ness), it soon occurred to me that my baseline energy levels increased.
Also, for the first time in years, I “slept like a baby” and woke up refreshed and ready to go. I realized that I had not gotten much of a benefit from caffeine but that I had mainly needed it to feel normal.
Once my sleep improved and my adrenal glands had readjusted to their natural rhythm, namely producing cortisol without caffeine as a gas pedal, I no longer required caffeine to wake up, and I also had considerably more energy throughout the day.
Since there is no difference in principle between (ab)using caffeine as a stimulant compared to other less socially accepted molecules that do not benefit from the familiarity principle, I decided that I am better off rotating caffeine with other stimulants, at the time ephedrine and modafinil.
I now use caffeine and other stimulants only very strategically, about once per week or less. For me, the short video “Nuggets” sums up my experience with caffeine pretty well.
In sum, caffeine is an excellent stimulant & focus compound without preexisting tolerance. However, for me, tolerance and counterregulation set in super fast and I soon need caffeine to feel “normal”. I think that I may be uniquely sensitive to it, more so than many other people.
Some of my friends swear by combining caffeine + L-theanine, both of which cancel out some of the negative effects of the other. I discuss my experience with L-theanine in more detail here.
How it works
Caffeine is an alkaloid produced by some plant species, such as the plants we use for coffee, cocoa, or tea production. These plants synthesize caffeine to poison invertebrate herbivores, mainly insects. Purely coincidentally, caffeine has stimulant effects on the vertebrate central nervous system.
Caffeine is an antagonist of various adenosine receptors. Adenosine is a chemical used for a variety of bodily processes, such as paracrine cell signaling and intracellular energy homeostasis.
In the hypothalamus, more specifically the ventrolateral preoptic area (VLPO), adenosine accumulates with prolonged wakefulness exerting sleep pressure. Among other things, this has an inhibitory effect on a variety of neurotransmitter systems.
Furthermore, and independent of its effects in the hypothalamus, adenosine also is a neuromodulator, inhibiting the release of dopamine in the mesolimbic dopamine system, among others.
If caffeine is consumed, these actions of adenosine are inhibited. Sleep pressure is antagonized, and a variety of neurotransmitters increase, among them histamine, dopamine, serotonin, noradrenaline, acetylcholine, and glutamate. The disinhibition of dopamine specifically causes a slight pleasure reaction (“liking”) as well as an increase in motivation, focus, and cognition.
Similar to other stimulants, caffeine reduces fatigue and sleepiness. Furthermore, caffeine improves memory, learning, reaction time, and athletic power output. Used sporadically, caffeine is also a powerful euphoriant and a large cup of coffee is enough to get caffeine virgins “wired”.
When I was interning in psychiatry, almost everyone was drinking a lot of caffeinated beverages. This may be a mostly subconscious effort to elevate brain dopamine levels, which are usually neglected by psychiatric regimens. More on the brutal neglect of dopamine here.
Overall thoughts on caffeine
Few people seem to use caffeine strategically, such as only a few times per week in low doses. As with any other stimulant, there is not just tolerance but counterregulation (the concept of counterregulation is explained here).
Most of the people who drink coffee habitually can attest to the unfortunate fact that the counterregulation to caffeine is quite strong. This means that most, but not all, chronic caffeine consumers get little benefits, but mainly need it to feel “normal”.
The neuroscientist Andrew Huberman recommends “delaying caffeine consumption for 90 minutes after waking up”. In my opinion, this is bad advice as many chronic caffeine drinkers have a blunted morning cortisol release anyway.
One of the upsides of caffeine is that we know for certain that even extensive life-long consumption is mostly safe, and perhaps even associated with beneficial effects – which cannot be said with such certainty for most of the other molecules discussed on this website.
However, many of its beneficial health-promoting effects, such as a reduction of liver cancer, stem from the many polyphenols (antioxidants) found in black coffee, tea, or dark chocolate. In fact, for many people with a shitty diet, coffee is the major dietary source of antioxidants.
Should I use caffeine?
Tim Ferris reportedly skyrocketed his productivity after cutting down caffeine consumption to only one cup of green tea per day.
In my opinion, many people use caffeine at far too high doses and far too often. Unfortunately, many people claim that they need caffeine to be functional human beings. However, they may underestimate the negative effects of habitual high caffeine intake on general alertness.
Regular daily caffeine intake is not just associated with disturbed sleep but also with increased daytime sleepiness, in part due to the combined effects of reduced morning cortisol secretion, impaired sleep, and the brain’s counterregulation to the effects of caffeine.
Given this is something that might affect how people feel and perform for years, I believe that most people would be well served to self-experiment whether they feel better with or without caffeine after an uncomfortable 2–3-week wash-out period.
Fortunately, tolerance and counter-regulation to caffeine go away as fast as they build up. Switching to decaf may help.
I have a couple of friends who went without consuming caffeine for extended periods of time. Some of them reportedly feel and function better by regularly drinking 1-2 cups of coffee per day compared to not consuming caffeine at all. We are all different.
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Pharmacology 101
Normally, signaling systems are mainly activated locally. However, when a molecule makes its way into the bloodstream, for example by oral administration, it comes in touch with all cells. It then acts on all of the cells that express receptors for which the molecule has an affinity. These receptors are then activated, partially activated, or inactivated – depending on the effect of the molecule on a certain receptor.
For example, if caffeine makes it into the bloodstream it is distributed via the circulatory system to every cell of the body. Caffeine then acts on all of the trillions of adenosine receptors, more technically the A1, A2A, A2B, and A3 receptors, throughout the body.
Caffeine does not just act where I want it to act – namely, in the ventrolateral preoptic area in the hypothalamus and the dopamine neurons in the ventral tegmentum. Caffeine also acts on blood vessels, kidneys, the heart, and many other tissues.
As an adenosine receptor antagonist, caffeine also acts on blood vessels as a general vasodilator, on cerebral blood vessels as a vasoconstrictor (hence the headache upon withdrawal), on the kidney as a diuretic, and on the heart as a cardiostimulant, among others.
Under physiological conditions, adenosine receptors in these organs are activated independently of each other since adenosine is a paracrine mediator in many bodily tissues. However, if caffeine is put into the bloodstream all of the adenosine receptors are acted on in one go.
However, as is the case with its effects on the central nervous system, there is strong tolerance and counterregulation to these effects if caffeine is consumed daily.
Other experience reports
Other stimulants:
- Modafinil
- Caffeine
- Nicotine
- Hydrocortisone
- Selegiline
- Methylphenidate
- Amphetamine
- Lisdexamphetamine
- Ephedrine
- Reboxetine
For a discussion of the molecular correlates of well-being, and links to accounts of various related molecules I have experimented with, read here.
For a full list of experience reports click here.
Sources & further information
- Scientific review: Caffeine: Cognitive and Physical Performance Enhancer or Psychoactive Drug?
- Website: Wikipedia – Caffeine
- Anecdote: Why I Quit Caffeine And How It Changed My Life
Disclaimer
The content available on this website is based on the author’s individual research, opinions, and personal experiences. It is intended solely for informational and entertainment purposes and does not constitute medical advice. The author does not endorse the use of supplements, pharmaceutical drugs, or hormones without the direct oversight of a qualified physician. People should never disregard professional medical advice or delay in seeking it because of something they have read on the internet.