Tolerance is the diminishing effect of a drug after repeated use, so that the user needs larger doses to achieve the same effect. It develops through changes in how the body metabolises the drug, how receptors respond, or how the nervous system adapts to the drug's presence.

Three main types are recognised: metabolic tolerance (the liver breaks the drug down faster), pharmacodynamic tolerance (receptors become less responsive), and behavioural tolerance (the user learns to compensate for the drug's effects). Cross-tolerance occurs when tolerance to one drug reduces the effect of another in the same class.

Key points

• Requires larger doses for the same effect
• Can be metabolic, pharmacodynamic, or behavioural
• Contributes to dependence and overdose risk
• Differs from withdrawal, which occurs after use stops