Reverse tolerance

Addiction and dependence glossary[1][2][3][4]
• addiction – a medical condition characterized by compulsive engagement in rewarding stimuli despite adverse consequences
• addictive behavior – a behavior that is both rewarding and reinforcing
• addictive drug – a drug that is both rewarding and reinforcing
• 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 that involves emotional–motivational withdrawal symptoms (e.g., dysphoria and anhedonia)
• reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them
• rewarding stimuli – stimuli that the brain interprets as intrinsically positive or as something to be approached
• 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

Reverse tolerance or drug sensitization is the phenomenon of a reversal of the side-effects from a drug, the reduction of insensitivity caused after drug tolerance has been established, or, in some cases, an increase in specific effects of a single drug existing alongside a tolerance to other effects of the same substance.^[5][6] Typically this involves the use of additional medication or abstinence from a drug for a period of time, known as a drug holiday. Such drugs include amphetamines and SSRIs.^[7][8]

As a result, regular users commonly experience a quick decrease of unwanted side effects, without an equivalent loss of its stimulant properties.

See also

• Desensitization (medicine)
• Downregulation and upregulation

References

1. Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 364–375. ISBN 9780071481274.
2. Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues Clin. Neurosci. 15 (4): 431–443. PMC 3898681. PMID 24459410.
3. "Glossary of Terms". Mount Sinai School of Medicine. Department of Neuroscience. Retrieved 9 February 2015.
4. Volkow ND, Koob GF, McLellan AT (January 2016). "Neurobiologic Advances from the Brain Disease Model of Addiction". N. Engl. J. Med. 374 (4): 363–371. doi:10.1056/NEJMra1511480. PMID 26816013.
5. Cross reverse tolerance between amphetamine, cocaine and morphine.
6. Drugs & Death : Profiles of illegal drug abuse. Joseph C. Rupp, M.D., Ph.D.
7. Leith N, Kuczenski R (1981). "Chronic amphetamine: tolerance and reverse tolerance reflect different behavioral actions of the drug.". Pharmacol Biochem Behav. 15 (3): 399–404. doi:10.1016/0091-3057(81)90269-0. PMID 7291243.
8. Chaudhry I, Turkanis S, Karler R (1988). "Characteristics of "reverse tolerance" to amphetamine-induced locomotor stimulation in mice.". Neuropharmacology. 27 (8): 777–81. doi:10.1016/0028-3908(88)90091-3. PMID 3216957.