Polysubstance use or multisubstance use is the use of combinations of psychoactive substances with both legal and illegal substances. This page lists polysubstance combinations that are entheogenic, recreational, or off-label indicated use of pharmaceuticals. For example, the over-the-counter motion sickness combination drug dimenhydrinate (8-chlorotheophylline/diphenhydramine) is occasionally used in higher doses as a deliriant. The prescription medicine Adderall (dextroamphetamine sulfate/amphetamine sulfate/dextroamphetamine saccharate/amphetamine aspartate monohydrate) is also frequently used recreationally. However, using non-prescribed drugs, using non-prescribed dose regimen, can cause polysubstance dependence, or combined drug intoxication which may lead to deaths.

To avoid an excessively long list, the table below only lists recreational drug combinations that are not patent medicine.