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      Craving in Opioid Use Disorder: From Neurobiology to Clinical Practice

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          Abstract

          Opioid use disorder (OUD) is a major public health issue that has reached epidemic levels in some parts of the world. It is a chronic and complex neurobiological disease associated with frequent relapse to drug taking. Craving, defined as an overwhelmingly strong desire or need to use a drug, is a central component of OUD and other substance use disorders. In this review, we describe the neurobiological and neuroendocrine pathways that underpin craving in OUD and also focus on the importance of assessing and treating craving in clinical practice. Craving is strongly associated with patients returning to opioid misuse and is therefore an important treatment target to reduce the risk of relapse and improve patients’ quality of life. Opioid agonist therapies (OAT), such as buprenorphine and methadone, can significantly reduce craving and relapse risk, and it is essential that patients are treated optimally with these therapies. There is also evidence to support the benefits of non-pharmacological approaches, such as cognitive behavioral therapy and mindfulness-based interventions, as supplementary treatments to opioid agonist therapies. However, despite the positive impact of these treatments on craving, many OUD patients continue to suffer with negative affect and dysphoria. There is a clear need for further studies to progress our understanding of the neurobiological basis of craving and addiction and to identify novel therapeutic strategies as well as to optimize the use of existing treatments to improve outcomes for the growing numbers of patients affected by OUD.

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          Neurobiologic Advances from the Brain Disease Model of Addiction.

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            Review. The incentive sensitization theory of addiction: some current issues.

            We present a brief overview of the incentive sensitization theory of addiction. This posits that addiction is caused primarily by drug-induced sensitization in the brain mesocorticolimbic systems that attribute incentive salience to reward-associated stimuli. If rendered hypersensitive, these systems cause pathological incentive motivation ('wanting') for drugs. We address some current questions including: what is the role of learning in incentive sensitization and addiction? Does incentive sensitization occur in human addicts? Is the development of addiction-like behaviour in animals associated with sensitization? What is the best way to model addiction symptoms using animal models? And, finally, what are the roles of affective pleasure or withdrawal in addiction?
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              Addiction and the brain antireward system.

              A neurobiological model of the brain emotional systems has been proposed to explain the persistent changes in motivation that are associated with vulnerability to relapse in addiction, and this model may generalize to other psychopathology associated with dysregulated motivational systems. In this framework, addiction is conceptualized as a cycle of decreased function of brain reward systems and recruitment of antireward systems that progressively worsen, resulting in the compulsive use of drugs. Counteradaptive processes, such as opponent process, that are part of the normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to repeatedly drive the allostatic state. Excessive drug taking thus results in not only the short-term amelioration of the reward deficit but also suppression of the antireward system. However, in the long term, there is worsening of the underlying neurochemical dysregulations that ultimately form an allostatic state (decreased dopamine and opioid peptide function, increased corticotropin-releasing factor activity). This allostatic state is hypothesized to be reflected in a chronic deviation of reward set point that is fueled not only by dysregulation of reward circuits per se but also by recruitment of brain and hormonal stress responses. Vulnerability to addiction may involve genetic comorbidity and developmental factors at the molecular, cellular, or neurocircuitry levels that sensitize the brain antireward systems.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                30 August 2019
                2019
                : 10
                : 592
                Affiliations
                [1] 1Department of Clinical Sciences, Psychiatry, Umeå University , Umeå, Sweden
                [2] 2Department of Public Health Solutions, The Alcohol, Drugs and Addictions Unit, National Institute of Health and Welfare , Helsinki, Finland
                [3] 3Division of Population and Behavioural Science, School of Medicine, University of St Andrews , St Andrews, United Kingdom
                [4] 4Centro de Atencion a las Adicciones de Arganzuela, Madrid Salud, Ayuntamiento de Madrid , Madrid, Spain
                [5] 5Director Penitentiary Medicine and Drug Abuse Unit, Health Care Unit Padua , Padua, Italy
                [6] 6Medical Affairs, Indivior UK Ltd , Slough, United Kingdom
                Author notes

                Edited by: Luigi Janiri, Catholic University of the Sacred Heart, Italy

                Reviewed by: Chiara Montemitro, G. d’Annunzio University of Chieti and Pescara, Italy; Oussama Kebir, Institut National de la Santé et de la Recherche Médicale (INSERM), France

                *Correspondence: Johan Kakko, johan.kakko@ 123456regionvasterbotten.se

                This article was submitted to Addictive Disorders, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2019.00592
                6728888
                31543832
                b4f368a7-0a6c-40a2-9342-fc02df05dced
                Copyright © 2019 Kakko, Alho, Baldacchino, Molina, Nava and Shaya

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 April 2019
                : 26 July 2019
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 146, Pages: 12, Words: 5572
                Categories
                Psychiatry
                Review

                Clinical Psychology & Psychiatry
                opioid,craving,addiction,negative affect,methadone,buprenorphine
                Clinical Psychology & Psychiatry
                opioid, craving, addiction, negative affect, methadone, buprenorphine

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