Michael Dickens has read the research and performed two self-experiments on whether consuming caffeine builds up tolerance, and if yes, how quickly.
What if instead of taking caffeine every day, you only take it intermittently—say, once every 3 days? How often can most people take caffeine without developing a tolerance?
The scientific literature on this question is sparse. Here’s what I found:
Experiments on rats found that rats who took caffeine every other day did not develop a tolerance. There are no experiments on humans. There are no experiments that use other intermittent dosing frequencies (such as once every 3 days).
Internet forum users report that they can take caffeine on average once every 3 days without developing a tolerance. But there’s a lot of variation between individuals.
If you take caffeine every day, does it stop working? If it keeps working, how much of its effect does it retain?
There are many studies on this question, but most of them have severe methodological limitations. I read all the good studies (on humans) I could find. Here’s my interpretation of the literature:
Caffeine almost certainly loses some but not all of its effect when you take it every day.
In expectation, caffeine retains 1⁄2 of its benefit, but this figure has a wide credence interval.
The studies on cognitive benefits all have some methodological issues so they might not generalize.
There are two studies on exercise benefits with strong methodology, but they have small sample sizes.
First experiment:
I conducted an experiment on myself to see if I would develop a tolerance to caffeine from taking it three days a week. The results suggest that I didn’t. Caffeine had just as big an effect at the end of my four-week trial as it did at the beginning.
This outcome is statistically significant (p = 0.016), but the data show a weird pattern: caffeine’s effectiveness went up over time instead of staying flat. I don’t know how to explain that, which makes me suspicious of the experiment’s findings.
Second experiment:
This time I tested if I could have caffeine 4 days a week without getting habituated.
Last time, when I took caffeine 3 days a week, I didn’t get habituated but the results were weird. This time, with the more frequent dose, I still didn’t get habituated, and the results were weird again! […] But it looks like I didn’t get habituated when taking caffeine 4 days a week—or, at least, not to a detectable degree. So I’m going to keep taking caffeine 4 days a week.
When I take caffeine 3 days in a row, do I habituate by the 3rd day?
The evidence suggests that I don’t, but the evidence is weak.
I’m fascinated that caffeine is so well-established (the most popular drug?) and yet these kinds of self-experiments still seem to add value over the scientific literature.
Anyway, I have a suspicion that tolerance builds at different rates for different effects. For example, if you haven’t had any caffeine in a long time (like months), it seems to create a strong sense of euphoria. But this seems to fade very quickly. Similarly, with prescription stimulants, people claim that tolerance to physical effects happens gradually, but full tolerance never develops for the effect on executive function. (Though I don’t think there are any long-term experiments to prove this.)
These different tolerances are a bit hard to understand mechanistically: Doesn’t caffeine only affect adenosine receptors? Maybe the body also adapts at different places further down the causal chain.
I’ve been running a bunch of experiments on this myself and I think it’s true that if you don’t go above doing it every other day on average you don’t get addicted. You still get homeostasis effects of being more tired (more adenocine receptors) without coffee. I think it’s therefore a very good positive reinforcer for productive behaviour, especially if used strategically.
Thank you for this post! Regarding the effectiveness going up, I think this is right. I don’t have an exact resource to back up this claim (probably mentioned in this episode), but I am quite sure that Huberman mentioned that regular caffeine consumption increases the amount of dopamine receptors in one’s brain, which allows more dopamine to bind. I am not confident on my explanation here, but I just wanted to share an idea based on what I have heard.