Polysubstance use or poly drug use refers to the use of combined psychoactive substances. Polysubstance use may be used for entheogenic, recreational, or off-label indications, with both legal and illegal substances. In many cases one drug is used as a base or primary drug, with additional drugs to leaven or compensate for the side effects, or tolerance, of the primary drug and make the experience more enjoyable with drug synergy effects, or to supplement for primary drug when supply is low.

A psychoactive drug, psychopharmaceutical, psychoactive agent, or psychotropic drug is a chemical substance that changes the function of the nervous system and results in alterations of perception, mood, cognition, and behavior. These substances have various applications, including medical use like psychedelic therapy, recreationally, or for spiritual reasons. Some categories of psychoactive drugs may be prescribed by physicians and other healthcare practitioners because of their therapeutic value.