tolerance

Meaning: Tolerance is a diminished effect of a substance when it is taken repeatedly, so the user needs more to reach the original effect. Causes include fewer or less sensitive receptors (downregulation), faster metabolism from increased enzyme activity, and compensatory changes in neural activity. Tolerance can also be partly learned. Cues linked to drug use, such as a room or a ritual, come to trigger compensatory responses that oppose the drug, which is a classical conditioning account. Biology uses the word differently: immune tolerance is the immune system not attacking self antigens.

On the MCAT: A passage describes a person or animal needing escalating doses, or a graph shows the response falling across repeated equal doses. You may be asked to predict that the same dose now has less effect. A common twist is that taking the usual dose in a new setting can produce a stronger effect, because the conditioned compensatory response is missing. Tolerance and withdrawal are the two features used to identify physiological dependence.

Common confusion: Tolerance is not the same as withdrawal or addiction. Tolerance is the reduced effect during continued use. Withdrawal is the set of symptoms after use stops or drops. Addiction involves compulsive use despite harm, and tolerance can occur without it. Tolerance is also not sensitization, where repeated exposure increases the response.