Drug tolerance

Drug tolerance or drug insensitivity is a pharmacological concept describing subjects' reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drug's effects; however, this may accelerate tolerance, further reducing the drug's effects. Drug tolerance is indicative of drug use but is not necessarily associated with drug dependence or addiction. The process of tolerance development is reversible (e.g., through a drug holiday) and can involve both physiological factors and psychological factors.

This article is about human resistance to the effects of drugs. For pathogenic resistance to the effects of drugs, see Drug resistance.
Addiction and dependence glossary
  • addiction – a biopsychosocial disorder characterized by persistent use of drugs (including alcohol) despite substantial harm and adverse consequences
  • addictive drug – psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain reward systems
  • dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
  • drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose
  • drug withdrawal – symptoms that occur upon cessation of repeated drug use
  • physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens)
  • psychological dependence – dependence socially seen as being extremely mild compared to physical dependence (e.g., with enough willpower it could be overcome)
  • reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them
  • rewarding stimuli – stimuli that the brain interprets as intrinsically positive and desirable or as something to approach
  • sensitization – an amplified response to a stimulus resulting from repeated exposure to it
  • substance use disorder – a condition in which the use of substances leads to clinically and functionally significant impairment or distress
  • tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose

One may also develop drug tolerance to side effects, in which case tolerance is a desirable characteristic. A medical intervention that has an objective to increase tolerance (e.g., allergen immunotherapy, in which one is exposed to larger and larger amounts of allergen to decrease one's allergic reactions) is called drug desensitization.

The opposite concept to drug tolerance is drug reverse tolerance (or drug sensitization), in which case the subject's reaction or effect will increase following its repeated use. The two notions are not incompatible and tolerance may sometimes lead to reverse tolerance. For example, heavy drinkers initially develop tolerance to alcohol (requiring them to drink larger amounts to achieve a similar effect) but excessive drinking can cause liver damage, which then puts them at risk of intoxication when drinking even very small amounts of alcohol.

Drug tolerance should not be confused with drug tolerability, which refers to the degree to which overt adverse effects of a drug can be tolerated by a patient.

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