These combinations are not usually physically harmful, but may produce undesirable effects. Use caution.
Note: Stimulants increase respiration rate allowing for a higher dose of sedatives than normal. If cocaine wears off first, recreational dosages of DPH may overcome the individual and cause respiratory arrest. Both substances at recreational dosages strain the heart and may lead to further dangerous heart complications. When taken together, both substances can potentially be more reinforcing and have greater risk of methemoglobinemia when higher dosages of DPH are combined with cocaine.
Substances in these categories
Cocaine
Diphenhydramine
Sources
- Drugs may be Induced Methemoglobinemia. Journal of Hematology & Thromboembolic Diseases, 06(01). (2017) — Alanazi, M. Q.
- Behavioral and neurochemical effects of cocaine and diphenhydramine combinations in rhesus monkeys. Psychopharmacology, 205(3), 467–474. (2009) — Banks, M. L., Andersen, M. L., Murnane, K. S., Meyer, R. C., & Howell, L. L.
- Diphenhydramine [Online post]. Drug-Forum. (2021) — chrisn
- Methaemoglobinaemia Associated With Mixed Cocaine and Amphetamine Overdose: A Case Report. Cureus, 16(1), e51748. (2024) — Eshmandi, M., Mohamed, A., Khalil, B., & Belhaj, A.
- Diphenhydramine toxicity: comparisons of postmortem findings in diphenhydramine-, cocaine-, and heroin-related deaths. The American Journal of Forensic Medicine and Pathology, 19(2), 143–147. (1998) — Karch, S. B.
- The effects pf cocaine and diphenhydramine upon the reactivity of rat vas deferens to supramaximal doses of noradrenaline and of other agonists: The mode of action of cocaine. European Journal of Pharmacology, 35(2), 333–339. (1976) — Pennefather, J. N.
- Cocaine and Cardiotoxicity: A Literature Review. Cureus, 13(4), e14594. (2021) — Pergolizzi, J. V., Magnusson, P., LeQuang, J. A. K., Breve, F., & Varrassi, G.
- Diphenhydramine. In StatPearls. StatPearls Publishing. (2025) — Sicari, V., Patel, P., & Zabbo, C. P.
- Cocaine-Like Neurochemical Effects of Antihistaminic Medications. Journal of Neurochemistry, 106(1), 147–157. (2008) — Tanda, G., Kopajtic, T. A., & Katz, J. L.
- Self-administration of cocaine-antihistamine combinations: Super-additive reinforcing effects. European Journal of Pharmacology, 557(2–3), 159–160. (2007) — Wang, Z., & Woolverton, W. L.
- Super-additive interaction of the reinforcing effects of cocaine and H1-antihistamines in rhesus monkeys. Pharmacology Biochemistry and Behavior, 91(4), 590–595. (2009) — Wang, Z., & Woolverton, W. L.
- Acute Management of Cocaine-Associated Methaemoglobinaemia. Case Reports in Medicine, 2011, 1–3. (2011) — Weichert, I.
Interaction Matrix
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These drugs work together to cause an effect greater than the sum of its parts. They aren't likely to cause an adverse or undesirable reaction when used carefully.
Effects are additive. The combination is unlikely to cause any adverse or undesirable reaction beyond those that might ordinarily be expected from these drugs.
One substance may reduce or counteract some of the effects of the other.
These combinations are not usually physically harmful, but may produce undesirable effects. Use caution.
There is considerable risk of physical harm when combining these substances. Use extreme caution.
These combinations are considered dangerous and should be avoided.
The interactions between these substances are not well documented.