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Diphenhydramine (Benadryl)

Antihistamineoral · inferred

First-generation antihistamine that crosses the blood-brain barrier, causing sedation. Used for allergies, insomnia, and motion sickness.

Projected serum levels — 25 mg, as needed (shown daily)

Diphenhydramine (Benadryl)
Diphenhydramine (Benadryl) modeled serum levels, 25 mg as needed (shown daily) over 15 days Population-based pharmacokinetic estimate. Steady state reached after approximately 1 days. 0 5 10 15 20 Day 0 Day 4 Day 8 Day 11 Day 15 Time on a regular schedule ≈ steady state · day 1
Diphenhydramine (Benadryl) modeled serum levels with a loading dose of 30.0 mg, then 25 mg as needed (shown daily) The first dose is larger so levels approach steady state faster. 0 5 10 15 20 Day 0 Day 4 Day 8 Day 11 Day 15 Time on a regular schedule

Maintenance schedule: 25 mg as needed (shown daily) (oral).

Loading schedule: 30.0 mg on day 1, then 25 mg as needed (shown daily) — reaching therapeutic levels sooner.

Modeled steady state after ~1 days: peak ≈ 18.1 mg, trough ≈ 3.6 mg body load. Population-based estimate over 15 days for a 25 mg dose at a 70 kg reference body mass — the interactive app scales curves to your doses, timing, and body mass.

Key facts

Category
Antihistamine
Route modeled
Oral
Model confidence
inferred
Half-life
9 h
Common dose
25 mg
Suggested maximum
300 mg/day
Reference dose range
12.5–300 mg (single dose)
Suggested cadence
as needed (shown daily)
Validated against
50 mg oral — Cmax 0.083 mg/L at 2.3 h

Documented interactions

  • danger
    1P-LSD (1-Propionyl-LSD) + Diphenhydramine (Benadryl) Serotonin risk

    1P-LSD (1-Propionyl-LSD) and Diphenhydramine (Benadryl) both have serotonergic activity. Risk of serotonin syndrome (hyperthermia, rigidity, autonomic instability, altered mental status).

  • danger
    25I-NBOMe + Diphenhydramine (Benadryl) Serotonin risk

    25I-NBOMe and Diphenhydramine (Benadryl) both have serotonergic activity. Risk of serotonin syndrome (hyperthermia, rigidity, autonomic instability, altered mental status).

  • danger
    2C-I (2,5-Dimethoxy-4-iodophenethylamine) + Diphenhydramine (Benadryl) Serotonin risk

    2C-I (2,5-Dimethoxy-4-iodophenethylamine) and Diphenhydramine (Benadryl) both have serotonergic activity. Risk of serotonin syndrome (hyperthermia, rigidity, autonomic instability, altered mental…

  • danger
    2C-B (4-Bromo-2,5-dimethoxyphenethylamine) + Diphenhydramine (Benadryl) Serotonin risk

    2C-B (4-Bromo-2,5-dimethoxyphenethylamine) and Diphenhydramine (Benadryl) both have serotonergic activity. Risk of serotonin syndrome (hyperthermia, rigidity, autonomic instability, altered mental…

  • danger
    4-AcO-DMT (Psilacetin) + Diphenhydramine (Benadryl) Serotonin risk

    4-AcO-DMT (Psilacetin) and Diphenhydramine (Benadryl) both have serotonergic activity. Risk of serotonin syndrome (hyperthermia, rigidity, autonomic instability, altered mental status).

  • danger
    4-MMC (Mephedrone) + Diphenhydramine (Benadryl) CYP inhibition

    Diphenhydramine (Benadryl) reversible_inhibitor of CYP2D6 predicted to change 4-MMC (Mephedrone) AUC by ~2.27x

Serum checks 261 modeled interaction pairings for diphenhydramine (benadryl) across your whole stack — absorption conflicts, enzyme inhibition, and nutrient depletion included.

Research behind this entry

  1. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study Gray SL et al. · JAMA Internal Medicine, 2015 DOI

    Prospective cohort of 3,434 adults aged 65+ found higher cumulative anticholinergic use (including diphenhydramine) was associated with increased dementia risk.

  2. Antihistamines for the common cold De Sutter AI et al. · Cochrane Database of Systematic Reviews, 2015 DOI

    Cochrane review found first-generation antihistamines like diphenhydramine provided small short-term improvements in cold symptoms (sneezing, rhinorrhea) but caused significant sedation.

  3. Diphenhydramine as a sleep aid: efficacy and side effects Morin CM et al. · Journal of Clinical Psychiatry, 2005 DOI

    Review noting diphenhydramine reduces sleep latency initially but develops rapid tolerance within 3-4 days, with residual daytime sedation and anticholinergic side effects.

3 published studies referenced in the app, each with a plain-language summary.