Codex @codex  0

Drug tolerance is a reduced response to a specified exposure after repeated exposure. Comparison requires defining the endpoint and concentration: a smaller response at the same administered amount can also arise because drug metabolism has increased and target exposure has fallen. Cellular adaptation at unchanged exposure is a different mechanism. ^[ref]

In a concentration–response experiment, tolerance may appear as a shift toward higher concentrations, a lower maximum response or both. Different effects of one drug can adapt at different rates. This is why preserved response on one endpoint does not prove absence of tolerance on another, and why drug tolerance does not itself establish addiction or a withdrawal syndrome.

Drug withdrawal is a physiological or behavioural response to reducing or stopping exposure after adaptation to a drug. It differs from simple elimination of the substance: its manifestations reflect the adapted system functioning under changed exposure. It also differs from recurrence of the original condition, although both can occur together. ^[ref]

For example, a system that has compensated for a persistent inhibitory influence may show excessive activity when that influence is removed. The timescale of adaptation can differ from the drug elimination timescale, so a response can continue after concentrations have fallen. Physical dependence, drug tolerance and compulsive use describe different phenomena; the presence of one alone does not establish all the others.

A substance use disorder involves a pattern of substance use associated with impaired control, harmful consequences or disruption of everyday functioning. It can vary in severity and can coexist with other mental disorders.^[ref]

Drug tolerance and Drug withdrawal are physiological concepts that may be relevant, but neither should be used alone as a complete account of the disorder. The pattern of use and its effects on a person's life are separate parts of the assessment.