Field of Science

Half-awake, half-life

I had a moderate allergic reaction to peanuts last night. I took diphenhydramine (Benadryl) and the hives had subsided by this morning. Lecturing on perturbation theory was more challenging. I felt like I was walking in a fog. Which got me to wondering, just what was the half-life of Benadryl? Benadryl has a relatively long half-life, between 8 and 10 hours. A typical 50 mg dose leads to a peak blood level of around 80 nanograms/ml. Most people feel drowsy at blood levels around 30 nanograms/ml. Assuming first order kinetics apply to the breakdown/elimination of Benadryl, a 30 nanogram/ml is not unlikely 10 to 15 hours later. Which would certainly explain my fogged state this morning! But not so foggy as to be unable to work the kinetics....


  1. Interesting. This explains why summer passed me by in a haze of diphenhydramine!
    For some reason I thought the half life was relatively rapid and I was just responding strangely.

  2. I had to stop taking benadryl for allergies unless I was planning on staying home for a day -- it just makes it too hard to work!

  3. I'm one of the lucky people who do not get sleepy from antihistamines. Any idea why it doesn't affect me? I guess the real question should be why does it put you in a fog?

    By the way, the abbreviation for liter is upper case, i.e. L. Thus the abbreviation for milliliter is mL not ml. This became official back in the 1970s and published in the Federal Register which has the final say since liter is a uniquely American unit.

    1. That is false. There’s no difference in meaning between liter and litre nor, for that matter, between meter and metre.

  4. If you take it enough you should build up a tolerance. Take often in the evening and the fog will subside by the time you awake in the morning...

  5. Just a note on the mechanism of brain fog. Diphenhydramine is a non-selective histamine receptor antagonist - it blocks histamine receptors. Newer second-generation antihistamines, in contrast to diphenhydramine, do not easily pass the 'blood brain barrier' (BBB). The BBB is created by astrocyte (support cells in the brain that are not actually neurons, or brain cells that can fire in the same way that neurons can) foot processes that line the blood vessels of the brain, enabling selectivity of what actually enters the tissue of the brain. After crossing the BBB, diphenhydramine blocks histamine receptors, most importantly those in the cerebral cortex. Histamine is actually produced in the hypothalamus and released in the cortex as one of the many overlapping systems that maintains wakefulness. So, blockade of these receptors makes you feel sleepy.
    Another reason is that diphenhydramine also blocks some types of acetylcholine receptors, less powerfully than blocking histamine receptors. Nonetheless, in high doses, diphenhydramine blocks these receptors, again within the cortex, resulting in decreased 'cortical activation'. This will result in some cognitive impairment and, possibly, some reduction in memory formation. Several brain regions that maintain wakefulness depend on acetylcholine. The anticholinergic action of diphenhydramine is also responsible for some degree of inhibition of saliva release and a dry mouth.


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