Addiction

Addiction
Other namesSevere substance use disorder[1][2]
PET images showing brain metabolism in drug addicts vs controls
Brain positron emission tomography images that compare brain metabolism in a healthy individual and an individual with a cocaine addiction
SpecialtyPsychiatry
Addiction and dependence glossary[3][4][5][2]
  • 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 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 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

Addiction is a biopsychosocial disorder characterized by repeated use of drugs, or repetitive engagement in a behavior such as gambling, despite harm to self and others.[3][5][2][6][7][8] According to the "brain disease model of addiction," while a number of psychosocial factors contribute to the development and maintenance of addiction, a biological process that is induced by repeated exposure to an addictive stimulus is the core pathology that drives the development and maintenance of an addiction.[3] Many scholars who study addiction argue that the brain disease model is incomplete and misleading.[9][10][11][12][13][14]

The brain disease model posits that addiction is a disorder of the brain's reward system which arises through transcriptional and epigenetic mechanisms and develops over time from chronically high levels of exposure to an addictive stimulus (e.g., eating food, the use of cocaine, engagement in sexual activity, participation in high-thrill cultural activities such as gambling, etc.).[3][15][16] DeltaFosB (ΔFosB), a gene transcription factor, is a critical component and common factor in the development of virtually all forms of behavioral and drug addictions.[15][16][17][18] Two decades of research into ΔFosB's role in addiction have demonstrated that addiction arises, and the associated compulsive behavior intensifies or attenuates, along with the overexpression of ΔFosB in the D1-type medium spiny neurons of the nucleus accumbens.[3][15][16][17] Due to the causal relationship between ΔFosB expression and addictions, it is used preclinically as an addiction biomarker.[3][15][17] ΔFosB expression in these neurons directly and positively regulates drug self-administration and reward sensitization through positive reinforcement, while decreasing sensitivity to aversion.[note 1][3][15]

Addiction exacts an "astoundingly high financial and human toll" on individuals and society as a whole.[19][20][21] In the United States, the total economic cost to society is greater than that of all types of diabetes and all cancers combined.[21] These costs arise from the direct adverse effects of drugs and associated healthcare costs (e.g., emergency medical services and outpatient and inpatient care), long-term complications (e.g., lung cancer from smoking tobacco products, liver cirrhosis and dementia from chronic alcohol consumption, and meth mouth from methamphetamine use), the loss of productivity and associated welfare costs, fatal and non-fatal accidents (e.g., traffic collisions), suicides, homicides, and incarceration, among others.[19][20][21][22] Classic hallmarks of addiction include impaired control over substances or behavior, preoccupation with substance or behavior, and continued use despite consequences.[23] Habits and patterns associated with addiction are typically characterized by immediate gratification (short-term reward), coupled with delayed deleterious effects (long-term costs).[24]

Examples of drug and behavioral addictions include alcoholism, marijuana addiction, amphetamine addiction, cocaine addiction, nicotine addiction, opioid addiction, food addiction, chocolate addiction, video game addiction, gambling addiction, and sexual addiction. The only behavioral addiction recognized by the DSM-5 and the ICD-10 is gambling addiction. With the introduction of the ICD-11 gaming addiction was appended.[25] The term addiction is misused frequently to refer to other compulsive behaviors or disorders, particularly dependence, in news media.[26] An important distinction between drug addiction and dependence is that drug dependence is a disorder in which cessation of drug use results in an unpleasant state of withdrawal, which can lead to further drug use.[27] Addiction is the compulsive use of a substance or performance of a behavior that is independent of withdrawal. Addiction can occur in the absence of dependence, and dependence can occur in the absence of addiction, although the two often occur together.

  1. ^ "Facing Addiction in America: The Surgeon General's Report on Alcohol, Drugs, and Health" (PDF). Office of the Surgeon General. US Department of Health and Human Services. November 2016. pp. 35–37, 45, 63, 155, 317, 338. Retrieved 28 January 2017.
  2. ^ a b c 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.
  3. ^ a b c d e f g 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.
  4. ^ 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.
  5. ^ a b "Glossary of Terms". Mount Sinai School of Medicine. Department of Neuroscience. Retrieved 9 February 2015.
  6. ^ Angres DH, Bettinardi-Angres K (October 2008). "The disease of addiction: origins, treatment, and recovery". Disease-A-Month. 54 (10): 696–721. doi:10.1016/j.disamonth.2008.07.002. PMID 18790142.
  7. ^ Cite error: The named reference NHM addiction-reward-reinforcement was invoked but never defined (see the help page).
  8. ^ Cite error: The named reference Reward system and psychostimulants was invoked but never defined (see the help page).
  9. ^ Hammer R, Dingel M, Ostergren J, Partridge B, McCormick J, Koenig BA (1 July 2013). "Addiction: Current Criticism of the Brain Disease Paradigm". AJOB Neuroscience. 4 (3): 27–32. doi:10.1080/21507740.2013.796328. PMC 3969751. PMID 24693488.
  10. ^ Heather N, Best D, Kawalek A, Field M, Lewis M, Rotgers F, Wiers RW, Heim D (4 July 2018). "Challenging the brain disease model of addiction: European launch of the addiction theory network". Addiction Research & Theory. 26 (4): 249–255. doi:10.1080/16066359.2017.1399659.
  11. ^ Heather N (1 April 2017). "Q: Is Addiction a Brain Disease or a Moral Failing? A: Neither". Neuroethics. 10 (1): 115–124. doi:10.1007/s12152-016-9289-0. PMC 5486515. PMID 28725283.
  12. ^ Satel S, Lilienfeld SO (2014). "Addiction and the brain-disease fallacy". Frontiers in Psychiatry. 4: 141. doi:10.3389/fpsyt.2013.00141. PMC 3939769. PMID 24624096.
  13. ^ Peele S (December 2016). "People Control Their Addictions: No matter how much the "chronic" brain disease model of addiction indicates otherwise, we know that people can quit addictions - with special reference to harm reduction and mindfulness". Addictive Behaviors Reports. 4: 97–101. doi:10.1016/j.abrep.2016.05.003. PMC 5836519. PMID 29511729.
  14. ^ Henden E (2017). "Addiction, Compulsion, and Weakness of the Will: A Dual-Process Perspective.". In Heather N, Gabriel S (eds.). Addiction and Choice: Rethinking the Relationship. Oxford, UK: Oxford University Press. pp. 116–132.
  15. ^ a b c d e Ruffle JK (November 2014). "Molecular neurobiology of addiction: what's all the (Δ)FosB about?". Am. J. Drug Alcohol Abuse. 40 (6): 428–37. doi:10.3109/00952990.2014.933840. PMID 25083822. S2CID 19157711.
    The strong correlation between chronic drug exposure and ΔFosB provides novel opportunities for targeted therapies in addiction (118), and suggests methods to analyze their efficacy (119). Over the past two decades, research has progressed from identifying ΔFosB induction to investigating its subsequent action (38). It is likely that ΔFosB research will now progress into a new era – the use of ΔFosB as a biomarker. ...
    Conclusions
    ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a molecular switch (34). As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124). Some of these proposed interventions have limitations (125) or are in their infancy (75). However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction.
  16. ^ a b c Cite error: The named reference Natural and drug addictions was invoked but never defined (see the help page).
  17. ^ a b c Biliński P, Wojtyła A, Kapka-Skrzypczak L, Chwedorowicz R, Cyranka M, Studziński T (2012). "Epigenetic regulation in drug addiction". Ann. Agric. Environ. Med. 19 (3): 491–96. PMID 23020045. For these reasons, ΔFosB is considered a primary and causative transcription factor in creating new neural connections in the reward centre, prefrontal cortex, and other regions of the limbic system. This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to relapse even after long periods of abstinence. These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken ... In this way, the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3. A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine. This depends on ΔFosB inhibiting G9a gene expression, i.e. H3K9me2 synthesis which in turn inhibits transcription factors for ΔFosB. For this reason, the observed hyper-expression of G9a, which ensures high levels of the dimethylated form of histone H3, eliminates the neuronal structural and plasticity effects caused by cocaine by means of this feedback which blocks ΔFosB transcription
  18. ^ Cite error: The named reference Nestler was invoked but never defined (see the help page).
  19. ^ a b Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 1: Basic Principles of Neuropharmacology". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 4. ISBN 978-0-07-148127-4. Drug abuse and addiction exact an astoundingly high financial and human toll on society through direct adverse effects, such as lung cancer and hepatic cirrhosis, and indirect adverse effects –for example, accidents and AIDS – on health and productivity.
  20. ^ a b Merikangas KR, McClair VL (June 2012). "Epidemiology of Substance Use Disorders". Hum. Genet. 131 (6): 779–89. doi:10.1007/s00439-012-1168-0. PMC 4408274. PMID 22543841.
  21. ^ a b c Cite error: The named reference ABAM was invoked but never defined (see the help page).
  22. ^ "Economic consequences of drug abuse" (PDF). International Narcotics Control Board Report: 2013 (PDF). United Nations – International Narcotics Control Board. 2013. ISBN 978-92-1-148274-4. Retrieved 28 September 2018.
  23. ^ Morse RM, Flavin DK (August 1992). "The definition of alcoholism. The Joint Committee of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism". JAMA. 268 (8): 1012–14. doi:10.1001/jama.1992.03490080086030. PMID 1501306.
  24. ^ Marlatt GA, Baer JS, Donovan DM, Kivlahan DR (1988). "Addictive behaviors: etiology and treatment". Annu Rev Psychol. 39: 223–52. doi:10.1146/annurev.ps.39.020188.001255. PMID 3278676.
  25. ^ Gansner ME (12 September 2019). "Gaming Addiction in ICD-11: Issues and Implications". Psychiatric Times. Retrieved 3 March 2020.
  26. ^ American Psychiatric Association (2013). "Substance-Related and Addictive Disorders" (PDF). American Psychiatric Publishing. pp. 1–2. Archived from the original (PDF) on 15 August 2015. Retrieved 10 July 2015. Additionally, the diagnosis of dependence caused much confusion. Most people link dependence with "addiction" when in fact dependence can be a normal body response to a substance.
  27. ^ Cite error: The named reference NHMH_3e terms-DSM flaw was invoked but never defined (see the help page).


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