"The effects of caffeine consumption do not decay with a ~5 hour half-life" by kman
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What is the main topic discussed in this episode?
The effects of caffeine consumption do not decay with a roughly five-hour half-life. By Kman. Published on April 8, 2026. Epistemic status.
Confident in the overall picture, substantial quantitative uncertainty about the relative potency of caffeine and paroxanthine. TLDR. The effects of caffeine consumption last longer than many assume. Paroxanthine is sort of like caffeine that behaves the way many mistakenly believe caffeine behaves. You've probably heard that caffeine exerts its psychostimulatory effects by blocking adenosine receptors. That matches my understanding, having dug into this. I'd also guess that, insofar as you've thought about the duration of caffeine's effects, you've thought of them as decaying with a roughly five-hour half-life. I used to think this, and every effect duration calculator I've seen assumes it, even this fancy one based on a complicated model that includes circadian effects.
But this part is probably wrong. very little circulating caffeine is directly excreted. Instead, it's converted, metabolized, into other similar molecules, primary metabolites, which themselves undergo further steps of metabolism, into secondary, tertiary, etc. metabolites, before reaching a form where they're efficiently excreted. Importantly, the primary metabolites also block adenosine receptors. In particular, more than 80% of circulating caffeine is metabolized into paroxanthine, which has a comparable binding affinity at adenosine receptors to caffeine itself. Paroxanthine then has its own 3-5 hour half-life as it's metabolized into a handful of other things. Since paroxanthine is by far the dominant primary metabolite, and its further metabolites are mostly either very short-lived or have poor affinity for adenosine receptors, we can fruitfully use a simplified model of caffeine-paroxanthine elimination.
The upshot is an effective concentration curve with a broader peak and slower decline about twice as long to reach half of peak effective concentration, assuming paroxanthine and caffeine are equipotent than that given by the simple elimination model. When I say effective concentration, I mean the concentration of caffeine that would be needed to produce the same effect. Below is a simulator that models caffeine and paroxanthine metabolism following ingestion of 100 mg caffeine or paroxanthine, linked to full version. Note that the relative potency of paroxanthine can be adjusted. I am uncertain about how it compares to caffeine within that fourfold window, see the section on relative potency.
There's an interactive widget here in the post. Heading. Paroxanthine supplements.
If the above model is correct, paroxanthine itself is sort of like caffeine that behaves the way I mistakenly used to believe caffeine behaves. Directly using paroxanthine as a stimulant would have two major differences advantages compared to caffeine. 1. Effects wear off a lot faster, which means you can take it later in the day without affecting sleep as much, or in the morning without affecting a siesta as much. 2. For a given peak level of stimulation you probably develop less tolerance, since active molecules don't hang around as long, really just another implication of point 1. It might also have some other differences, like a somewhat different profile of effects. In the US you can buy paroxanthine itself as a supplement, I believe it only became available recently, in 2022.
I've been using 100mg capsules intermittently in the last few weeks. Some early impressions There's a list of bullet points here. Taking one or two capsules in the morning has a similar wakefulness-promoting effect to drinking a cup or two of coffee in the morning. I've taken one capsule around 4 to 5 p.m. a handful of times, which did not interfere with going to sleep at 10 to 11 p.m. Taking a capsule at 7 p.m. gave me enough energy to do some work in the evening and did not interfere with going to sleep at 11.30 p.m.
How does caffeine's metabolism affect its effects?
Subjectively, the peak effects of 100 mg paroxanthine feel similar or weaker than those of 100 mg caffeine, while 200 mg paroxanthine feels stronger than 100 mg caffeine.
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