| Addiction and dependence glossary[1][2][3] | |
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Reverse toleranceordrug sensitization is a pharmacological phenomenon describing subjects' increased reaction (positive or negative) to a drug following its repeated use.[4] Not all drugs are subject to reverse tolerance.
This is the opposite of drug tolerance, in which the effect or the subject's reaction decreases 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 as excessive drinking can cause liver damage, this can then put this group at risk of intoxication when drinking even very small amounts of alcohol.[5] Sensitization, a form of reverse tolerance, develops rapidly to the positive, euphoric effects of alcohol, but not to the physical effects, such as sedation and respiratory depression, which diminish with prolonged use. This sensitization does not occur, however, with administration of benzodiazepines or neuroactive steroids, which only exhibit weakening of effect with repeated use.
Reverse tolerance can also occur in users of stimulants such as cocaine or amphetamines. A previously recreational dose may become enough to cause psychosis in regular users, or users who previously had a psychotic episode may be more likely to have one in the future and at lower doses once drug usage continues.[6]
In some cases drug sensitization may also refer to medical interventions (e.g. a drug holiday) that aim to reduce the insensitivity caused by drug tolerance.
Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.
Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder.
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