Substance
What not to mix with Diphenhydramine (Benadryl)
Deliriant
Also calledbenadryl, dph, sleep aid, zzzquil, unisom, doxylamine
Summary
Diphenhydramine is checked against 40 other substances — 8 dangerous, 11 unsafe and 17 caution.
Dangerous
8- Diphenhydramine and AlcoholAt everyday doses, studies find diphenhydramine makes alcohol's hit to coordination and reaction time much worse, and you will not feel how impaired…
- Diphenhydramine and GHB / GBLEach makes the other much stronger, raising the risk of memory loss, collapse and unconsciousness. Do not combine. If someone passes out, put them on…
- Diphenhydramine and KetamineEach makes the other stronger: people pass out without warning, and ketamine can push diphenhydramine into delirium. Do not combine at recreational…
- Diphenhydramine and MephedroneAt recreational doses this risks serotonin syndrome and heart trouble, and if one wears off first the other can overwhelm you. Do not combine.
- Diphenhydramine and MXEThis risks serotonin syndrome and sudden unconsciousness, and MXE can push diphenhydramine into delirium. Do not combine at recreational doses. If…
- Diphenhydramine and PCPTogether they cause heavy delirium and memory loss, often with behaviour you will not remember. Do not combine.
- Diphenhydramine and SSRIsAt recreational doses of diphenhydramine this carries a high risk of serotonin syndrome. Do not combine at recreational doses.
- Diphenhydramine and TramadolBoth add to the risk of serotonin syndrome, and diphenhydramine may raise tramadol's seizure risk. Do not combine at recreational doses.
Unsafe
11- Diphenhydramine and BenzodiazepinesEach makes the other stronger, so people pass out without warning and black out. Avoid this combination beyond low medical doses. If someone passes…
- Diphenhydramine and BuprenorphineEach makes the other stronger, raising the risk of memory loss, collapse and unconsciousness. Avoid this combination. Keep naloxone nearby.
- Diphenhydramine and CodeineEach makes the other stronger, raising the risk of memory loss, collapse and unconsciousness. Avoid this combination. Keep naloxone nearby.
- Diphenhydramine and DXMDiphenhydramine raises DXM levels, and together they risk serotonin syndrome, delirium, overheating and heart strain. Avoid this combination at…
- Diphenhydramine and FentanylEach makes the other stronger, raising the risk of memory loss, collapse and unconsciousness. Avoid this combination. Keep naloxone nearby.
- Diphenhydramine and KratomEach makes the other stronger, raising the risk of memory loss, collapse and unconsciousness. Avoid this combination. Keep naloxone nearby.
- Diphenhydramine and MAOIsThis carries a real risk of serotonin syndrome, and MAOIs can make diphenhydramine stronger and longer-lasting. Avoid this combination at…
- Diphenhydramine and MDMADiphenhydramine stops you sweating, and overheating is the main way MDMA kills. Avoid this combination.
- Diphenhydramine and MethadoneEach makes the other stronger, raising the risk of memory loss, collapse and unconsciousness. Avoid this combination. Keep naloxone nearby.
- Diphenhydramine and OpioidsEach makes the other stronger, raising the risk of memory loss, collapse and unconsciousness. Avoid this combination. Keep naloxone nearby.
- Diphenhydramine and PregabalinThis carries a real seizure risk and makes passing out more likely. Avoid this combination at recreational doses.
Caution
17- Diphenhydramine and 2C-T-xTogether they add confusion and discomfort, and diphenhydramine makes 2C-T-x's nausea worse. Take less of each than usual, and do not use alone.
- Diphenhydramine and 2C-xDiphenhydramine tends to turn a trip confusing and unpleasant rather than stronger. Take less of each than usual, and do not use alone.
- Diphenhydramine and 5-MeO-xxTDelirium on top of a short, intense trip is disorienting and hard to manage. Take less of each than usual, and do not use alone.
- Diphenhydramine and AmphetaminesAmphetamines can hide how confused diphenhydramine is making you, and together they strain the heart. Keep diphenhydramine to ordinary medical doses.
- Diphenhydramine and AMTTogether they add confusion, and diphenhydramine stops you sweating while AMT heats you up. Take less of each than usual, and do not use alone.
- Diphenhydramine and CaffeineCaffeine can hide how confused diphenhydramine is making you, and together they strain the heart. Keep diphenhydramine to ordinary medical doses.
- Diphenhydramine and CannabisTogether they usually cause more confusion and anxiety than either alone. Take less of each than usual.
- Diphenhydramine and CocaineCocaine hides how sedated you are; if it wears off first, high doses of diphenhydramine can stop your breathing. Both strain the heart. Keep…
- Diphenhydramine and DMTBeyond an ordinary 25–50 mg dose of diphenhydramine, DMT makes its delirium worse and injury more likely. Keep diphenhydramine to that dose.
- Diphenhydramine and DOxBeyond an ordinary 25–50 mg dose of diphenhydramine, DOx makes its delirium worse and adds heart strain. Keep diphenhydramine to that dose.
- Diphenhydramine and LithiumHigher doses of diphenhydramine risk serotonin syndrome and heart-rhythm problems with lithium. Keep diphenhydramine to an ordinary 25–50 mg.
- Diphenhydramine and LSDBeyond an ordinary 25–50 mg dose of diphenhydramine, LSD makes its delirium worse and adds heart strain. Keep diphenhydramine to that dose.
- Diphenhydramine and MescalineBeyond an ordinary 25–50 mg dose of diphenhydramine, mescaline makes its delirium worse and injury more likely. Keep diphenhydramine to that dose.
- Diphenhydramine and MethamphetamineAmphetamines can hide how confused diphenhydramine is making you, and together they strain the heart. Keep diphenhydramine to ordinary medical doses.
- Diphenhydramine and MushroomsBeyond an ordinary 25–50 mg dose of diphenhydramine, mushrooms make its delirium worse and injury more likely. Keep diphenhydramine to that dose.
- Diphenhydramine and NBOMesBeyond an ordinary 25–50 mg dose of diphenhydramine, NBOMes make its delirium worse and add heart strain. Keep diphenhydramine to that dose.
- Diphenhydramine and Nitrous OxideTogether they add disorientation and the risk of falling, which lasts well past the nitrous. Take less of each than usual, and do not use alone.
Low / synergy
1Low / no synergy
3Checking more than one?
This page rates Diphenhydramine against one substance at a time. Combinations of three or more carry risks that no pair-by-pair list can show — the checker rates every pair at once and flags the whole-mix ones on top.
Open Diphenhydramine in the checkerEducational information only, not medical advice. Absence of a documented interaction is not evidence of safety. Combination data from the TripSit drug combination chart, retrieved 2026-08-20.