Mixing Diphenhydramine (Benadryl) and MXE
Dangerous
This risks serotonin syndrome and sudden unconsciousness, and MXE can push diphenhydramine into delirium. Do not combine at recreational doses. If someone passes out, put them on their side.
There is a high risk of serotonin syndrome from this combination. Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. MXE has a high likelihood of increasing DPH's deliriant effects at higher dosages and can greatly increase the risk of injury, mania, and psychosis. Medical dosages are unlikely 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 MXE?
MixSafe rates mixing Diphenhydramine and MXE as "Dangerous" — high risk of death or life-changing injury. Do not combine. Source: TripSit drug combination chart, retrieved 2026-08-20. Educational information, not medical advice.
- Diphenhydramine also called
- benadryl, dph, sleep aid, zzzquil, unisom, doxylamine
- MXE also called
- methoxetamine
TripSit drug combination chart, retrieved 2026-08-20. View the dataset.
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Rated dangerous. Educational information only, not medical advice. Absence of a documented interaction is not evidence of safety.