Medication·Interactions·Reviewed June 9, 2026
Diphenhydramine interactions.
Diphenhydramine has 4 documented interactions in the NutriStack database. The full interaction list is below. None of this is a substitute for your prescriber's advice.
Diphenhydramine at a glance.
A quick, data-grounded summary. The full tables are below.
Diphenhydramine has 4 documented interactions in the NutriStack database. The full interaction list is below. None of this is a substitute for your prescriber's advice.
Substances that interact with diphenhydramine.
Every supplement and medication in the NutriStack database with a documented interaction with this drug, highest-severity first. Open any pair for the mechanism and sources.
| Substance | Interaction | What happens |
|---|---|---|
| Alcohol | Caution | Alcohol can add to diphenhydramine's sedating and anticholinergic effects. Human testing found worse mental-performance impairment when ethanol was... details → |
| Cannabis (THC-Dominant) | Caution | THC-dominant cannabis can add to diphenhydramine-related drowsiness, slowed reaction time, and impaired attention. Cannabis acutely impairs... details → |
| Melatonin | Caution | Melatonin can add to diphenhydramine's sleepiness and next-day grogginess when both are used as sleep aids. Melatonin has documented short-term... |
| Valerian Root | Caution | Diphenhydramine can cause meaningful drowsiness, slowed reaction time, anticholinergic confusion, and driving impairment. Valerian root is commonly... |
The full diphenhydramine profile.
Uses, typical dosing, side effects, and the cited evidence for this medication.
Common diphenhydramine questions.
Quick answers drawn from the tables above.
What interacts with Diphenhydramine?
In the NutriStack database, Diphenhydramine has 4 documented interactions. The most notable include Alcohol, Cannabis (THC-Dominant), Melatonin, and Valerian Root. Check any specific combination before taking it and confirm with your prescriber.
Is it safe to take Alcohol with Diphenhydramine?
NutriStack classifies the Alcohol and Diphenhydramine pairing as caution: Alcohol can add to diphenhydramine's sedating and anticholinergic effects. Human testing found worse mental-performance impairment when ethanol was combined with... Avoid alcohol when you take diphenhydramine, including nighttime sleep-aid doses. Do not drive, operate machinery, or take extra sedatives if both... Always confirm with your prescriber.
Check your whole stack
See how diphenhydramine fits your supplements.
NutriStack screens your full routine for interactions and depletions, and updates the moment you change it.