Non-Opioid Treatments for Opioid Use Disorder: Rationales and Data to Date
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LEADING ARTICLE
Non‑Opioid Treatments for Opioid Use Disorder: Rationales and Data to Date Reda M. Chalhoub1,2 · Peter W. Kalivas1
© Springer Nature Switzerland AG 2020
Abstract Opioid use disorder (OUD) represents a major public health problem that affects millions of people in the USA and worldwide. The relapsing and recurring aspect of OUD, driven by lasting neurobiological adaptations at different reward centres in the brain, represents a major obstacle towards successful long-term remission from opioid use. Currently, three drugs that modulate the function of the opioidergic receptors, methadone, buprenorphine and naltrexone have been approved by the US Food and Drug Administration (FDA) to treat OUD. In this review, we discuss the limitations and challenges associated with the current maintenance and medication-assisted withdrawal strategies commonly used to treat OUD. We further explore the involvement of glutamatergic, endocannabinoid and orexin signaling systems in the development, maintenance and expression of addiction-like behaviours in animal models of opioid addiction, and as potential and novel targets to expand therapeutic options to treat OUD. Despite a growing preclinical literature highlighting the role of these potential targets in animal models of opioid addiction, clinical and translational studies for novel treatments of OUD remain limited and inconclusive. Further preclinical and clinical investigations are needed to expand the arsenal of primary treatment options and adjuncts to maximise efficacy and prevent relapse.
Key Points
1 Introduction
Currently, treatment approaches for opioid use disorder (OUD), through modulators of mu-opioid receptors, have several limitations.
Opioid addiction can be defined as a chronically relapsing neuropsychiatric disorder characterised by dysregulation of the brain reward systems leading to uncontrollable motivation to obtain opioids, and an increased propensity to relapse despite extended periods of abstinence [1]. As defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), opioid use disorder (OUD) is characterised by the chronic and sustained manifestation of several symptoms within a 12-month period, including withdrawal symptoms, tolerance development, and an uncontrollable desire to seek and use drugs despite negative consequences on the patient’s daily life [2]. The time course of this neuropsychiatric disorder is characterised by cycling periods of exacerbated use and abstinence over years, separated by periods of treatment and remission [3], during which the relapse vulnerability remains high due to sustained neuroadaptations to the brain’s reward circuitry following chronic exposure to opioids [1]. Opioid addiction represents a major public health disorder in the United States (US) and globally. According to the 2018 National Survey on Drug Use and Health (NSDUH), more than 800,000 people in the US report using heroin during the last year [4]. Furthermore, epidemiological studies
Substantial evidence from preclinic
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