These combinations are considered dangerous and should be avoided.
Note: There 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 possible to overdose due to the lack of counteraction. Medical dosages are reported not to be a concern for the general population. Both substances affect the heart and may lead to further dangerous heart complications at higher dosages. The combination may increase each other's side effects, such as dizziness and drowsiness. At higher dosages, the combination may increase each other's side effects, such as delirium, mania, and psychosis.
Substances in these categories
Diphenhydramine
Mephedrone
Sources
- Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027 (2025) — Clark, J. H., Meltzer, E. O., & Naclerio, R. M.
- Serotonin Syndrome and Other Serotonergic Disorders: Table 1. Pain Medicine, 4(1), 63-74 (2003) — Ener, R. A., Meglathery, S. B., Decker, W. A. V., & Gallagher, R. M.
- 4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse. The Journal of Pharmacology and Experimental Therapeutics, 339(2), 530-536 (2011) — Hadlock, G. C., Webb, K. M., McFadden, L. M., Chu, P. W., Ellis, J. D., Allen, S. C., Andrenyak, D. M., Vieira-Brock, P. L., German, C. L., Conrad, K. M., Hoonakker, A. J., Gibb, J. W., Wilkins, D. G., Hanson, G. R., & Fleckenstein, A. E.
- Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949-1958 (2011) — Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T.
- Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicology Letters, 208(1), 62-68 (2012) — Meng, H., Cao, J., Kang, J., Ying, X., Ji, J., Reynolds, W., & Rampe, D.
- Characterization of Diphenhydramine-Related Accidental Overdose Deaths. Academic Forensic Pathology, 5(1), 105-115 (2015) — Varghese, E., Abate, M. A., Hu, L., Kaplan, J., Kraner, J., Long, D. L., Sorg, M., Mock, A., Greenwald, M., & Andrew, T.
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.