Substance
What not to mix with Diphenhydramine
Deliriant
Also calledbenadryl, dph, sleep aid, zzzquil, unisom
Summary
Diphenhydramine is checked against 40 other substances — 8 dangerous, 11 unsafe and 17 caution.
Dangerous
8- Diphenhydramine and AlcoholThe two substances potentiate each other strongly and unpredictably, and may rapidly lead to unconsciousness. They both increase each other's side…
- Diphenhydramine and GHB / GBLBoth substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and…
- Diphenhydramine and KetamineBoth substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While…
- Diphenhydramine and MephedroneThere is a high risk of serotonin syndrome at recreational dosages. Both can dull each other's effects, so if one wears off before the other it's…
- Diphenhydramine and MXEThere is a high risk of serotonin syndrome from this combination. Both substances potentiate the ataxia and sedation caused by the other and can lead…
- Diphenhydramine and PCPConsistent with diphenhydramine's rating against other dissociatives: strongly additive delirium, confusion and amnesia, with a high chance of…
- Diphenhydramine and SSRIsThere is a high risk of serotonin syndrome at recreational dosages. Medical dosages are reported not to be a concern for the general population. The…
- Diphenhydramine and TramadolBoth drugs increase the risk of serotonin syndrome. While at medical dosages, this is unlikely to be of concern, recreational doses should be…
Unsafe
11- Diphenhydramine and BenzodiazepinesBoth substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While…
- Diphenhydramine and BuprenorphineBoth substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and…
- Diphenhydramine and CodeineBoth substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and…
- Diphenhydramine and DXMThe combination is reported to reduce the side effects of each drug and potentiate many of the recreational effects. There is a significant risk of…
- Diphenhydramine and FentanylBoth substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and…
- Diphenhydramine and KratomBoth substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and…
- Diphenhydramine and MAOIsThere is a significant risk of serotonin syndrome with this combination. Monoamine oxidase A inhibitors may extend and increase the anticholinergic…
- Diphenhydramine and MDMADiphenhydramine is a strong anticholinergic: it suppresses sweating and impairs the body's ability to shed heat. MDMA already raises body temperature…
- Diphenhydramine and MethadoneBoth substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and…
- Diphenhydramine and OpioidsBoth substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and…
- Diphenhydramine and PregabalinThere is a significant risk of seizures from this combination. The combination is likely to increase each other’s negative side effects, such as…
Caution
17- Diphenhydramine and 2C-T-xAdditive confusion and physical discomfort; diphenhydramine tends to make an already nausea-prone psychedelic worse.
- Diphenhydramine and 2C-xDiphenhydramine's deliriant character muddies psychedelic effects and commonly turns them confusing and unpleasant rather than enhancing them.
- Diphenhydramine and 5-MeO-xxTDeliriant effects combined with an intense, short psychedelic make for a disorienting and hard-to-manage experience.
- Diphenhydramine and AmphetaminesAmphetamines as a stimulant may mask some of the negative side effects of DPH, leading to delusions of sobriety which has additional concern in…
- Diphenhydramine and AMTAdditive confusion, plus anticholinergic suppression of sweating against AMT's stimulant load on body temperature.
- Diphenhydramine and CaffeineCaffeine as a stimulant may mask some negative side effects of DPH, leading to delusions of sobriety, which has additional concerns in states of…
- Diphenhydramine and CannabisBoth can produce confusion and, at higher doses, hallucination. Together they commonly produce more disorientation and anxiety than either alone.
- Diphenhydramine and CocaineStimulants increase respiration rate allowing for a higher dose of sedatives than normal. If cocaine wears off first, recreational dosages of DPH may…
- Diphenhydramine and DMTAt 25-50mg, DPH may assist with side effects of the DMT such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and DMT…
- Diphenhydramine and DOxAt 25-50mg, DPH may assist with side effects of DOx drugs such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and DOx…
- Diphenhydramine and LithiumThere is a concern of serotonin syndrome at higher dosages of this combination. Caution is recommended in restricting diphenhydramine to medical…
- Diphenhydramine and LSDAt 25-50mg, DPH may assist with side effects of the LSD such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and LSD…
- Diphenhydramine and MescalineAt 25-50mg, DPH may assist with side effects of the mescaline such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and…
- Diphenhydramine and MethamphetamineAmphetamines as a stimulant may mask some of the negative side effects of DPH, leading to delusions of sobriety which has additional concern in…
- Diphenhydramine and MushroomsAt 25-50mg, DPH may assist with side effects of the psilocybin such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH)…
- Diphenhydramine and NBOMesAt 25-50mg, DPH may assist with side effects of the NBOMe drugs such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH)…
- Diphenhydramine and Nitrous OxideAdditive dissociation and disorientation, with a raised risk of falling. Diphenhydramine's sedation makes the loss of coordination last well past the…
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.