탐닉

위키백과, 우리 모두의 백과사전.
둘러보기로 가기 검색하러 가기
탐닉 및 의존증 관련 용어[1][2][3][4]
탐닉 addiction 보수자극과 관련되어 부정적 결과에도 불구하고 충동적 행동을 하는 것으로 특징지어지는 뇌기능 장애
탐닉성 행동 addictive behavior 보상과 보강 작용을 동시에 일으키는 행동
탐닉성 약물 addictive drug 보상과 보강 작용을 동시에 일으키는 약물
의존 dependence 자극에 대한 지속적 자극을 중단할 경우 금단증후군을 동반하는 적응 상태
내성 tolerance 약물을 정량 반복적으로 사용했을 때 효과가 감소하는 것
역내성 reverse tolerance 약물을 정량 반복적으로 사용했을 때 효과가 증가하는 것
약물 금단 drug withdrawal 약물의 반복적 사용을 중단했을 때 나타나는 증상
신체의존 physical dependence 지속적인 육체적 금단증상(피로감, 섬망 등)을 나타내는 의존
심리의존 psychological dependence 심리정신적 금단증상(불쾌감, 무쾌감 등)을 나타내는 의존
보강자극 reinforcing stimuli 자극을 받으면 행동을 반복할 가능성을 증가시키는 자극
보수자극 rewarding stimuli 뇌가 본질적으로 긍정적이고 욕망하고자 하는 것으로 받아들이는 자극
민감화 sensitization 자극에 반복적으로 노출됨으로써 자극에 대한 반응이 증폭되는 것
약물사용장애 substance use disorder 약물을 사용함으로써 임상적 기능적으로 심각한 해로움이나 고통을 유발하는 상태
(편집 | 역사)

탐닉(耽溺, addiction)[5]은 부정적 결과에도 불구하고 보수계 자극의 충동적 작용을 거듭하는 것으로 특징지어지는 뇌기능 장애다.[9] 여러 가지 심리적 요인이 작용하지만, 기본적으로 탐닉성 자극에 반복적으로 노출됨으로써 진행되는 생물학적 과정이 탐닉을 유발하고 또한 유지시키는 기본적 병리라고 할 수 있다.[2][10] 모든 탐닉성 자극은 양성 보강 작용(i.e. 자극에 노출된 사람이 반복적으로 노출될 가능성을 높인다)과 본질적 보수성(i.e. 그 자체로 긍정적이거나 욕망의 대상이거나 쾌락을 유발하는 것으로 인지된다)을 특성으로 갖는다.[2][3][8] 탐닉을 흔히 중독이라고 부르는 경우가 많으나, 중독과 탐닉은 완전 다른 별개의 개념이다.

탐닉성이 있는 약물,
헤로인 병.

탐닉은 높은 수준의 탐닉성 자극(e.g. 약물, 성행위, 도박 등)에 만성적으로 노출됨으로써 전사후생유전적 기작을 통하여 발생하게 되는 뇌의 보수계의 장애이다.[2][11][12] 모든 행동탐닉 및 약물탐닉의 형성에는 유전자 전사 인자 중 하나인 ΔFosB가 치명적이고 공통적인 요인으로 작용한다.[11][12][13][14] 탐닉에 있어서 ΔFosB의 역할을 20여년 간 연구한 결과 탐닉의 발생과 그에 수반하는 충동적 행동이 전뇌 측좌핵D₁ 중형 다극신경원에 ΔFosB가 과잉 표현되는 것과 함께 나타난다는 것이 밝혀졌다.[2][11][12][13] ΔFosB 표현은 탐닉과의 사이에 이러한 인과성 상관관계가 있기에 탐닉의 전임상적 생물지표로 사용된다.[2][11][13] 이 신경원들에 ΔFosB가 표현됨으로써 약물의 자가투여와 보상 민감화가 양성 보강을 통해 증가함과 동시에 혐오성 민감도는 감소한다.[2][11]

탐닉증은 개인 및 사회에 지극히 큰 재산피해 및 인명피해를 입힌다. 그 피해에는 탐닉성 약물 자체의 직접적 해악과, 거기에 수반하는 의료비용, 장기적 합병증(e.g. 흡연으로 인한 폐암, 음주로 인한 간경화 등), 뇌의 신경가소성의 기능적 변형, 생산성의 총체적 저하 등이 모두 포함된다.[15][16][17] 탐닉의 고전적 특징으로는 특정 물질이나 행동에 대한 자제력 감손, 그 물질 또는 행동에 대한 집착, 그리고 부정적 결과에도 불구하고 사용을 멈출 수 없음 등이 꼽힌다.[18] 탐닉과 유관한 습관 및 행동양식은 일반적으로 즉각적 만족감(단기간적 보상)과 그에 비해 오래 지속되는 해로운 효과(장기간적 비용)으로 특징지어진다.[19]

각주[편집]

  1. Malenka RC, Nestler EJ, Hyman SE (2009). 〈Chapter 15: Reinforcement and Addictive Disorders〉. Sydor A, Brown RY. 《Molecular Neuropharmacology: A Foundation for Clinical Neuroscience》 2판. New York: McGraw-Hill Medical. 364–375쪽. ISBN 9780071481274. 
  2. Nestler EJ (December 2013). “Cellular basis of memory for addiction”. 《Dialogues Clin. Neurosci.》 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. 
  3. “Glossary of Terms”. 《Mount Sinai School of Medicine》. Department of Neuroscience. 2015년 2월 9일에 확인함. 
  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. PMID 26816013. doi:10.1056/NEJMra1511480. 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.
     
  5. “질병분류목록 :: 정신활성물질의 사용에 의한 정신 및 행동 장애(F10-F19)”. 질병분류 정보센터. 313-315쪽. 
  6. Angres DH, Bettinardi-Angres K (October 2008). “The disease of addiction: origins, treatment, and recovery”. 《Dis Mon》 54 (10): 696–721. PMID 18790142. doi:10.1016/j.disamonth.2008.07.002. 
  7. Malenka RC, Nestler EJ, Hyman SE (2009). 〈Chapter 15: Reinforcement and Addictive Disorders〉. Sydor A, Brown RY. 《Molecular Neuropharmacology: A Foundation for Clinical Neuroscience》 2판. New York: McGraw-Hill Medical. 364–365, 375쪽. ISBN 9780071481274. The defining feature of addiction is compulsive, out-of-control drug use, despite negative consequences. ...
    compulsive eating, shopping, gambling, and sex–so-called "natural addictions"–  Indeed, addiction to both drugs and behavioral rewards may arise from similar dysregulation of the mesolimbic dopamine system.
     
  8. Taylor SB, Lewis CR, Olive MF (February 2013). “The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans”. 《Subst. Abuse Rehabil.》 4: 29–43. PMC 3931688. PMID 24648786. doi:10.2147/SAR.S39684. 
  9. [2][3][4][6][7][8]
  10. American Society for Addiction Medicine (2012). “Definition of Addiction”. 
  11. Ruffle JK (November 2014). “Molecular neurobiology of addiction: what's all the (Δ)FosB about?”. 《Am. J. Drug Alcohol Abuse》 40 (6): 428–437. PMID 25083822. doi:10.3109/00952990.2014.933840.
    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.
     
  12. Olsen CM (December 2011). “Natural rewards, neuroplasticity, and non-drug addictions”. 《Neuropharmacology》 61 (7): 1109–1122. PMC 3139704. PMID 21459101. doi:10.1016/j.neuropharm.2011.03.010. Functional neuroimaging studies in humans have shown that gambling (Breiter et al, 2001), shopping (Knutson et al, 2007), orgasm (Komisaruk et al, 2004), playing video games (Koepp et al, 1998; Hoeft et al, 2008) and the sight of appetizing food (Wang et al, 2004a) activate many of the same brain regions (i.e., the mesocorticolimbic system and extended amygdala) as drugs of abuse (Volkow et al, 2004). ... Cross-sensitization is also bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA ... As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. The transcription factor delta FosB is increased in the NAc, PFC, dorsal striatum, and VTA following repeated sexual behavior (Wallace et al., 2008; Pitchers et al., 2010b). This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance, and NAc blockade of delta FosB attenuates this behavior (Hedges et al, 2009; Pitchers et al., 2010b). Further, viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience (Hedges et al., 2009). ... In some people, there is a transition from "normal" to compulsive engagement in natural rewards (such as food or sex), a condition that some have termed behavioral or non-drug addictions (Holden, 2001; Grant et al., 2006a). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al, 2006; Aiken, 2007; Lader, 2008)." 
    Table 1: Summary of plasticity observed following exposure to drug or natural reinforcers"
  13. 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): 491–496. 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 
  14. Robison AJ, Nestler EJ (November 2011). “Transcriptional and epigenetic mechanisms of addiction”. 《Nat. Rev. Neurosci.》 12 (11): 623–637. PMC 3272277. PMID 21989194. doi:10.1038/nrn3111. ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states. 
  15. Malenka RC, Nestler EJ, Hyman SE (2009). 〈Chapter 1: Basic Principles of Neuropharmacology〉. Sydor A, Brown RY. 《Molecular Neuropharmacology: A Foundation for Clinical Neuroscience》 2판. New York: McGraw-Hill Medical. 4쪽. ISBN 9780071481274. 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. 
  16. KR Merikangas KR, McClair VL (June 2012). “Epidemiology of Substance Use Disorders”. 《Hum. Genet.》 131 (6): 779–789. PMC 4408274. PMID 22543841. doi:10.1007/s00439-012-1168-0. 
  17. “AMERICAN BOARD OF MEDICAL SPECIALTIES RECOGNIZES THE NEW SUBSPECIALTY OF ADDICTION MEDICINE” (PDF). 《American Board of Addiction Medicine》. 2016년 3월 14일. 2016년 4월 3일에 확인함. Sixteen percent of the non-institutionalized U.S. population age 12 and over – more than 40 million Americans – meets medical criteria for addiction involving nicotine, alcohol or other drugs. This is more than the number of Americans with cancer, diabetes or heart conditions. In 2014, 22.5 million people in the United States needed treatment for addiction involving alcohol or drugs other than nicotine, but only 11.6 percent received any form of inpatient, residential, or outpatient treatment. Of those who do receive treatment, few receive evidence-based care. (There is no information available on how many individuals receive treatment for addiction involving nicotine.)
    Risky substance use and untreated addiction account for one-third of inpatient hospital costs and 20 percent of all deaths in the United States each year, and cause or contribute to more than 100 other conditions requiring medical care, as well as vehicular crashes, other fatal and non-fatal injuries, overdose deaths, suicides, homicides, domestic discord, the highest incarceration rate in the world and many other costly social consequences. The economic cost to society is greater than the cost of diabetes and all cancers combined. Despite these startling statistics on the prevalence and costs of addiction, few physicians have been trained to prevent or treat it.
     
  18. 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): 1012–4. PMID 1501306. doi:10.1001/jama.1992.03490080086030. 
  19. Marlatt GA, Baer JS, Donovan DM, Kivlahan DR (1988). “Addictive behaviors: etiology and treatment”. 《Annu Rev Psychol》 39: 223–52. PMID 3278676. doi:10.1146/annurev.ps.39.020188.001255.