The concept of "drug tolerance”, refers to the gradual decrease of a subject’s reaction and sensitivity to a psychoactive substance or drug, implying that progressively larger doses are required to achieve the desired effect.

Drug tolerance can involve both psychological drug tolerance as well as physiological factors. Kratom, which has both stimulant and sedative effects, induces a complex mechanism of physical tolerance, in which regular use tends to induce a diminishing of the opiate-like relaxant effect and therefore underline the more stimulant effects, especially at higher doses.