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      Historical Review: Opiate Addiction and Opioid Receptors

      review-article
      1
      Cell Transplantation
      SAGE Publications
      substance use disorders, opioid addiction, opioid receptors, methadone, buprenorphine, naloxone

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          Abstract

          Substance use disorders (SUDs), defined as a collection of symptoms including tolerance and withdrawal, are chronic illnesses characterized by relapse and remission. In the United States, billions of dollars have been lost due to SUDs. In the past 30 years, effective medications and behavioral interventions have played a major role in preventing relapse and facilitating longer periods of abstinence. From the late 1990s to the present, the opioid epidemic or opioid crisis in the United States has raised public awareness of SUDs. Methadone, buprenorphine, and naloxone have proven their effectiveness in treating addicted individuals, and each of them has different effects on different opioid receptors. Methadone and buprenorphine target mu opioid receptors (MORs) in the brain to treat opioid dependence by reducing withdrawal and craving, whereas naloxone is an opioid antagonist used to treat opioid overdose. Mu, kappa, and delta are opioid receptor subtypes with common analgesic effects, and each also has unique effects and distribution in the brain. MORs in distinct brain regions, such as the nucleus accumbens and basolateral amygdala, trigger the euphoria and incentive properties of rewarding stimuli. Kappa opioid receptors can trigger anti-reward effects and produce dysphoric effects. Delta opioid receptors can induce anxiolytic effects. Though effective medications are available, relapse is still common due to neurobiological changes in brain pathways and tolerance of opioid receptors with repeated abuse of substances. In this article, I summarize the biological mechanisms of opioid dependence and opioid receptors and review previous articles about medications used to treat SUDs and their clinical effects.

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          Most cited references51

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          Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation.

          The effects of drug dependence on social systems has helped shape the generally held view that drug dependence is primarily a social problem, not a health problem. In turn, medical approaches to prevention and treatment are lacking. We examined evidence that drug (including alcohol) dependence is a chronic medical illness. A literature review compared the diagnoses, heritability, etiology (genetic and environmental factors), pathophysiology, and response to treatments (adherence and relapse) of drug dependence vs type 2 diabetes mellitus, hypertension, and asthma. Genetic heritability, personal choice, and environmental factors are comparably involved in the etiology and course of all of these disorders. Drug dependence produces significant and lasting changes in brain chemistry and function. Effective medications are available for treating nicotine, alcohol, and opiate dependence but not stimulant or marijuana dependence. Medication adherence and relapse rates are similar across these illnesses. Drug dependence generally has been treated as if it were an acute illness. Review results suggest that long-term care strategies of medication management and continued monitoring produce lasting benefits. Drug dependence should be insured, treated, and evaluated like other chronic illnesses. JAMA. 2000;284:1689-1695.
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            Stigma, discrimination and the health of illicit drug users.

            Persons who use illicit drugs are stigmatized in the United States. The conferral of a deviant social status on illicit drug users may serve to discourage use. However, stigmatization may also adversely affect the health of those who use illicit drugs, through exposure to chronic stress such as discrimination and as a barrier to accessing care. We hypothesized that aspects of stigma and discrimination would be associated with mental and physical health among illicit drug users. Using street outreach techniques, 1008 illicit drug users were interviewed about stigma and discrimination related to their drug use, and their health. We measured discrimination related to drug use, alienation, perceived devaluation, and responses to discrimination and stigma. Health measures included mental and physical health measures from the Medical Outcomes Study Short Form-36, depression symptoms from the Center for Epidemiological Studies Depression scale, and a sum of health conditions. In adjusted models, discrimination and alienation were both associated with poorer mental health, and only discrimination was associated with poorer physical health. Angry responses to discrimination and stigma were associated with poorer mental health. The association of stigma and discrimination with poor health among drug users suggests the need for debate on the relative risks and benefits of stigma and discrimination in this context.
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              Societal costs of prescription opioid abuse, dependence, and misuse in the United States.

              The objective of this study was to estimate the societal costs of prescription opioid abuse, dependence, and misuse in the United States. Costs were grouped into three categories: health care, workplace, and criminal justice. Costs were estimated by 1) quantity method, which multiplies the number of opioid abuse patients by cost per opioid abuse patient; and 2) apportionment method, which begins with overall costs of drug abuse per component and apportions the share associated with prescription opioid abuse based on relative prevalence of prescription opioid to overall drug abuse. Excess health care costs per patient were based on claims data analysis of privately insured and Medicaid beneficiaries. Other data/information were derived from publicly available survey and other secondary sources. Total US societal costs of prescription opioid abuse were estimated at $55.7 billion in 2007 (USD in 2009). Workplace costs accounted for $25.6 billion (46%), health care costs accounted for $25.0 billion (45%), and criminal justice costs accounted for $5.1 billion (9%). Workplace costs were driven by lost earnings from premature death ($11.2 billion) and reduced compensation/lost employment ($7.9 billion). Health care costs consisted primarily of excess medical and prescription costs ($23.7 billion). Criminal justice costs were largely comprised of correctional facility ($2.3 billion) and police costs ($1.5 billion).   The costs of prescription opioid abuse represent a substantial and growing economic burden for the society. The increasing prevalence of abuse suggests an even greater societal burden in the future. Wiley Periodicals, Inc.
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                Author and article information

                Journal
                Cell Transplant
                Cell Transplant
                CLL
                spcll
                Cell Transplantation
                SAGE Publications (Sage CA: Los Angeles, CA )
                0963-6897
                1555-3892
                13 November 2018
                March 2019
                : 28
                : 3
                : 233-238
                Affiliations
                [1 ]Tsaotun Psychiatric Center, Ministry of Health and Welfare
                Author notes
                [*]Shaocheng Wang, Tsaotun Psychiatric Center, Ministry of Health and Welfare, No.161, Yuping Rd., Caotun Township, Nantou County 542. Email: swang118@ 123456jhu.edu
                Author information
                https://orcid.org/0000-0002-7009-5338
                Article
                10.1177_0963689718811060
                10.1177/0963689718811060
                6425114
                30419763
                2f418ad0-0d00-4d0a-a425-b3477b04dc1b
                © The Author(s) 2018

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 22 June 2018
                : 11 October 2018
                : 12 October 2018
                Categories
                Special Section on Addiction

                substance use disorders,opioid addiction,opioid receptors,methadone,buprenorphine,naloxone

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