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      Polysubstance use in the U.S. opioid crisis

      review-article
      1 , , 1 , 2
      Molecular Psychiatry
      Nature Publishing Group UK
      Addiction, Neuroscience

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          Abstract

          Interventions to address the U.S. opioid crisis primarily target opioid use, misuse, and addiction, but because the opioid crisis includes multiple substances, the opioid specificity of interventions may limit their ability to address the broader problem of polysubstance use. Overlap of opioids with other substances ranges from shifts among the substances used across the lifespan to simultaneous co-use of substances that span similar and disparate pharmacological categories. Evidence suggests that nonmedical opioid users quite commonly use other drugs, and this polysubstance use contributes to increasing morbidity and mortality. Reasons for adding other substances to opioids include enhancement of the high (additive or synergistic reward), compensation for undesired effects of one drug by taking another, compensation for negative internal states, or a common predisposition that is related to all substance consumption. But consumption of multiple substances may itself have unique effects. To achieve the maximum benefit, addressing the overlap of opioids with multiple other substances is needed across the spectrum of prevention and treatment interventions, overdose reversal, public health surveillance, and research. By addressing the multiple patterns of consumption and the reasons that people mix opioids with other substances, interventions and research may be enhanced.

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          Most cited references94

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          Neurocircuitry of addiction.

          Drug addiction is a chronically relapsing disorder that has been characterized by (1) compulsion to seek and take the drug, (2) loss of control in limiting intake, and (3) emergence of a negative emotional state (eg, dysphoria, anxiety, irritability) reflecting a motivational withdrawal syndrome when access to the drug is prevented. Drug addiction has been conceptualized as a disorder that involves elements of both impulsivity and compulsivity that yield a composite addiction cycle composed of three stages: 'binge/intoxication', 'withdrawal/negative affect', and 'preoccupation/anticipation' (craving). Animal and human imaging studies have revealed discrete circuits that mediate the three stages of the addiction cycle with key elements of the ventral tegmental area and ventral striatum as a focal point for the binge/intoxication stage, a key role for the extended amygdala in the withdrawal/negative affect stage, and a key role in the preoccupation/anticipation stage for a widely distributed network involving the orbitofrontal cortex-dorsal striatum, prefrontal cortex, basolateral amygdala, hippocampus, and insula involved in craving and the cingulate gyrus, dorsolateral prefrontal, and inferior frontal cortices in disrupted inhibitory control. The transition to addiction involves neuroplasticity in all of these structures that may begin with changes in the mesolimbic dopamine system and a cascade of neuroadaptations from the ventral striatum to dorsal striatum and orbitofrontal cortex and eventually dysregulation of the prefrontal cortex, cingulate gyrus, and extended amygdala. The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction.
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            CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016.

            This guideline provides recommendations for primary care clinicians who are prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care. The guideline addresses 1) when to initiate or continue opioids for chronic pain; 2) opioid selection, dosage, duration, follow-up, and discontinuation; and 3) assessing risk and addressing harms of opioid use. CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, and recommendations are made on the basis of a systematic review of the scientific evidence while considering benefits and harms, values and preferences, and resource allocation. CDC obtained input from experts, stakeholders, the public, peer reviewers, and a federally chartered advisory committee. It is important that patients receive appropriate pain treatment with careful consideration of the benefits and risks of treatment options. This guideline is intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death. CDC has provided a checklist for prescribing opioids for chronic pain (http://stacks.cdc.gov/view/cdc/38025) as well as a website (http://www.cdc.gov/drugoverdose/prescribingresources.html) with additional tools to guide clinicians in implementing the recommendations.
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              Prescription Opioid Use, Misuse, and Use Disorders in U.S. Adults: 2015 National Survey on Drug Use and Health

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                Author and article information

                Contributors
                wcompton@nida.nih.gov
                Journal
                Mol Psychiatry
                Mol Psychiatry
                Molecular Psychiatry
                Nature Publishing Group UK (London )
                1359-4184
                1476-5578
                13 November 2020
                13 November 2020
                2021
                : 26
                : 1
                : 41-50
                Affiliations
                [1 ]GRID grid.420090.f, ISNI 0000 0004 0533 7147, U.S. Department of Health and Human Service, , National Institute on Drug Abuse, National Institutes of Health, ; Bethesda, MD USA
                [2 ]Institute for Behavior and Health, Inc., Rockville, MD USA
                Author information
                http://orcid.org/0000-0003-3108-5118
                Article
                949
                10.1038/s41380-020-00949-3
                7815508
                33188253
                2b43cb5c-3d2a-4f3f-9818-7bd1e5bf4a0f
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 March 2020
                : 4 October 2020
                : 29 October 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000026, U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA);
                Award ID: DA Z999999
                Award Recipient :
                Categories
                Perspective
                Custom metadata
                © Springer Nature Limited 2021

                Molecular medicine
                addiction,neuroscience
                Molecular medicine
                addiction, neuroscience

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