Mixing Diphenhydramine (Benadryl) and Lithium
Caution
Higher doses of diphenhydramine risk serotonin syndrome and heart-rhythm problems with lithium. Keep diphenhydramine to an ordinary 25–50 mg.
There is a concern of serotonin syndrome at higher dosages of this combination. Caution is recommended in restricting diphenhydramine to medical dosages (25-50mg). Lithium and diphenhydramine both have concerns of QT prolongation which may be increased when taken in combination; risks increase due to a variety of factors such as the health of the user and drug dosages. Additionally, the combination may increase each drug's side effects, such as dizziness and loss of consciousness.
The risk here is to the experience — intensity, panic, thought loops, confusion. Physical harm is unlikely at ordinary doses. Setting, company and dose do most of the work.
Headspace vs physical riskCan you mix Diphenhydramine (Benadryl) and Lithium?
MixSafe rates mixing Diphenhydramine and Lithium as "Caution" — carries risk that is worth understanding before combining. Reduce doses and do not use alone. Source: TripSit drug combination chart, retrieved 2026-08-20. Educational information, not medical advice.
- Diphenhydramine also called
- benadryl, dph, sleep aid, zzzquil, unisom, doxylamine
- Lithium also called
- lithium carbonate, lithobid, mood stabilizer
TripSit drug combination chart, retrieved 2026-08-20. View the dataset.
Think this rating or note is wrong, or know a better source? Send it.
Checking more than two?
Combinations of three or more carry risks that no pair-by-pair chart can show. The checker rates every pair at once and flags the whole-mix ones on top.
Open this in the checkerRelated combinations
Rated caution. Educational information only, not medical advice. Absence of a documented interaction is not evidence of safety.