Mixing Diphenhydramine (Benadryl) and MAOIs
Unsafe
This carries a real risk of serotonin syndrome, and MAOIs can make diphenhydramine stronger and longer-lasting. Avoid this combination at recreational doses.
There is a significant risk of serotonin syndrome with this combination. Monoamine oxidase A inhibitors may extend and increase the anticholinergic effects of DPH. The combination increases each other’s side effects, such as drowsiness, dizziness, dry mouth, and headaches. Medical dosages are not reported to be of concern.
This combination carries bodily risk and can go badly psychologically. The headspace part often arrives first and makes the physical part harder to notice.
Headspace vs physical riskWhat to do
- Say what was taken and how much.Responders need it, and in most US states Good Samaritan laws protect both of you from drug possession charges when you call for an overdose.
- Unresponsive: put them on their side, tilt the head back, and stay until help arrives.Never leave someone alone to “sleep it off”.
- Never Use Alone 1-800-484-3731Stays on the line and sends help if you stop responding.
- Full steps: what to do if it is already happeningOverdose signs, the recovery position, what to say on the call, and whether you can be charged for making it.
- Poison Control 1-800-222-1222Free and 24/7, for “is this bad?” before it becomes an emergency.
Can you mix Diphenhydramine (Benadryl) and MAOIs?
MixSafe rates mixing Diphenhydramine and MAOIs as "Unsafe" — risk of serious physical or psychological harm. Not recommended under any circumstances. Source: TripSit drug combination chart, retrieved 2026-08-20. Educational information, not medical advice.
- Diphenhydramine also called
- benadryl, dph, sleep aid, zzzquil, unisom, doxylamine
- MAOIs also called
- maoi, nardil, phenelzine, parnate, tranylcypromine, marplan
TripSit drug combination chart, retrieved 2026-08-20. View the dataset.
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Rated unsafe. Educational information only, not medical advice. Absence of a documented interaction is not evidence of safety.