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
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Reverse tolerance or drug 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.
^Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 364–375. ISBN 9780071481274.
^Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues in Clinical Neuroscience. 15 (4): 431–443. PMC 3898681. PMID 24459410. 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.
^Volkow ND, Koob GF, McLellan AT (January 2016). "Neurobiologic Advances from the Brain Disease Model of Addiction". New England Journal of Medicine. 374 (4): 363–371. doi:10.1056/NEJMra1511480. PMC 6135257. PMID 26816013. 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.
Reversetolerance or drug sensitization is a pharmacological phenomenon describing subjects' increased reaction (positive or negative) to a drug following...
not incompatible and tolerance may sometimes lead to reversetolerance. For example, heavy drinkers initially develop tolerance to alcohol (requiring...
dependence. Heavy alcohol consumption over a period of years can lead to "reversetolerance". A liver can be damaged by chronic alcohol use, leading to a buildup...
Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant...
both rewarding and reinforcing. ... Familiar pharmacologic terms such as tolerance, dependence, and sensitization are useful in describing some of the time-dependent...
increased effect of drug following repeated doses (the opposite of drug tolerance). Such sensitization involves changes in brain mesolimbic dopamine transmission...
A zero tolerance policy is one which imposes a punishment for every infraction of a stated rule. Zero tolerance policies forbid people in positions of...
origin. Dextromethorphan has been noted to slow the development of and reversetolerance to opioids, as well as to exert additional analgesia by acting upon...
exposure to a stimulus (e.g., drug intake) drug sensitization or reversetolerance – the escalating effect of a drug resulting from repeated administration...
down-regulation due to continual drug stimulation, producing 'liking' tolerance. Incentive-sensitization would produce addiction, by selectively magnifying...
defines a situation in which one has developed one or more of either tolerance, withdrawal symptoms, drug seeking behaviors, such as continued use despite...
benzodiazepine binding sites (tolerance/dependence), while etizolam caused an increase in alpha-2 benzodiazepine binding sites (reversetolerance to anti-anxiety effects)...
of the following criteria must be manifest during a 12-month period: Tolerance Withdrawal symptoms or clinically defined alcohol withdrawal syndrome...
immunoreactivity in the striatum or other parts of the reward system. Drug tolerance develops rapidly in amphetamine abuse (i.e., recreational amphetamine...
[verification needed] Tolerance is expected to develop with regular methamphetamine use and, when used recreationally, this tolerance develops rapidly. In...
user may want the drug more and more while liking it less and less as tolerance develops to the drug's pleasurable effects. Amphetamine improves task...
the reverse engineering of a cylinder head, which includes freeform cast features, such as water jackets and high-tolerance machined areas. Reverse engineering...
Immune tolerance, also known as immunological tolerance or immunotolerance, refers to the immune system's state of unresponsiveness to substances or tissues...
elicits its stimulating effects via several distinct actions: it inhibits or reverses the transporter proteins for the monoamine neurotransmitters (namely the...
and sensitivity of these receptors, a process called desensitization or tolerance. Sensitization and desensitization are more likely to occur with long-term...
dependence may be diagnosed. Compulsive and repetitive use may result in tolerance to the effect of the drug and withdrawal symptoms when use is reduced...
Cannabinoid Type 1 Receptors in Dopamine D2 Receptor Knockout Mice Is Reversed by Chronic Forced Ethanol Consumption". Alcoholism: Clinical and Experimental...
exposure to a stimulus (e.g., drug intake) drug sensitization or reversetolerance – the escalating effect of a drug resulting from repeated administration...
dormancy do not divide. The tolerance shown in persister cells differs from antimicrobial resistance in that the tolerance is not inherited and is reversible...
immunoreactivity in the striatum or other parts of the reward system. Drug tolerance develops rapidly in amphetamine abuse (i.e., recreational amphetamine...
exposure to a stimulus (e.g., drug intake) drug sensitization or reversetolerance – the escalating effect of a drug resulting from repeated administration...
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