Mixing Diphenhydramine (Benadryl) and Pregabalin (Lyrica)
Unsafe
This carries a real seizure risk and makes passing out more likely. Avoid this combination at recreational doses.
There is a significant risk of seizures from this combination. The combination is likely to increase each other’s negative side effects, such as nausea, dizziness, and loss of consciousness. At higher dosages, pregabalin is likely to increase diphenhydramine’s deliriant effects, inhibition, and risk of injury. Medical dosages are not reported to be a 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 Pregabalin (Lyrica)?
MixSafe rates mixing Diphenhydramine and Pregabalin 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
- Pregabalin also called
- lyrica, pregablin, gabapentin, gaba, neurontin, gabbies
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.