At 25 mg, one trial could not tell the drug from a dummy pill
37 volunteers aged 21 to 76 took one 25 mg dose or a dummy and were tracked for 24 hours. Sedation, mood, performance and memory looked the same either way.
What the study found
One 25 mg dose was indistinguishable from placebo in 37 people
Half a sleep-aid dose behaved like nothing at all. Thirty-seven volunteers aged 21 to 76 took a single 25 mg dose of diphenhydramine or a dummy and were tracked for 24 hours on sedation, mood, performance and memory. Young and old alike, drug and dummy could not be told apart.
The caveat · Too few people to rule out an effect
This is an absence of detected difference, not a measured absence of effect. Thirty-seven people in a crossover design has limited power and the abstract states no power calculation. A single dose in volunteers with no sleep complaint, so nothing here speaks to taking it every night.
What we don't know
What would settle this is one study testing 25 mg and 50 mg of diphenhydramine side by side, and nobody has run it. Until then, where between the two doses impairment begins is unknown.