Contents lists available at ScienceDirect Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns Review Article Medication-assisted therapies for opioid use disorders in patients with chronic pain Tyler S. Oesterle a, ⁎ , Bhanu Prakash Kolla a , Teresa A. Rummans a , Mark S. Gold b a Mayo Clinic – Rochester, Department of Psychiatry & Psychology, 200 First Street SW, Rochester, MN 55905, United States of America b Washington University in St Louis, School of Medicine, St Louis, MO, United States of America ABSTRACT Opioids have been used to treat pain and invoke pleasure for centuries. Modern scientific advancements have led to more potent, synthetic opioids. While certainly more effective in treating pain, they can also be much more addictive. Over the years the scientific community has developed a clearer understanding of the role opioidreceptorsplayincausingandtreatingopioidusedisorders(OUD)andwenowknowthatOUDcandevelopinindividualstakingopioidsfor“legitimate”pain. Current guidelines suggest that all prescribers (especially those prescribing opioids) be capable treating OUD. Pharmacological advances have led to a wide array of safe and effective treatment options to address OUDs. This paper will discuss the history of opioid development, what is known about the transition from analgesic uses to addiction and modern evidenced based treatment strategies to address OUDs. 1. History of opioid development Opioids have been utilized by humans for centuries for both med- icinal and recreational purposes. The name opioid, meaning “opium like,” was derived from the Greek “opos” (meaning juice) referencing the milky white liquid that exudes from the opium poppy. By the se- venth to eighth century A.D., Arab traders brought opium to India and China and it did not take too long for trading routes to allow dis- tribution to all parts of Europe. During this time it was sold both as an intoxicant and for medicinal uses. A pivotal step in our understanding of opioids as neurochemical agents occurred when the active in- gredients of the opium poppy (morphine, codeine and thebaine) were isolated in the early 1800s [1]. The most potent active ingredient in opiumdubbed“morphine”aftertheGreekgodofdreamswasrelatively easy to produce for chemists. Furthermore, its chemical processing by western scientists added a degree of medical “authenticity” to opium that was previously known more as an intoxicant in the west [2]. After isolating morphine, it would take another 50 years before its full chemical formula was identified [1]. Morphine's basic structure (protonated amine connected to an aromatic ring in a specific or- ientation)wouldbecomeacommonfeatureforfutureopioidstudyand synthesis [3,4]. By the late 1800s, their nociceptive properties were well established, but opioids were also found in many tinctures purported as treatments for a broad range of ailments. This broad ap- plication and medicinal legitimacy lead to decades of overuse, rampant addiction, and a broad search for “safer” substitutes. Ironically, heroin was first derived in 1898 as part of a concerted effort to find a safer opioid.Itwasheraldedwithmuchfanfareasamorepotentopioidthan morphine and yet “free from abuse liability” [5]. Approximately 100 years later the same verbiage would be used by modern pharma- ceutical companies to aggressively advertise oxycodone (thought to be one of many significant factors contributing to our modern opioid epidemic) [6,7]. In 1939 mepiridine was discovered as the first fully synthetically derived compound shown to affect the opioid receptor [8]. Its discovery set off a wave of new synthetic opioid related dis- coveries over the next few years including the synthesis of methadone in 1946 [9]. In the 1960s there was a growing understanding of the biochemistry of the brain which led to a push to better understand the biological pathways associated with the opioid class of medications. By 1973, several researchers showed that opioids bound in the brain in a structurally specific manner and in “non-uniform” distributions [5]. In 1976aseriesofexperimentsdefinitivelydemonstrated3distinctopioid receptorsthatwereoriginallynamedaftertheexperimentalopioidthat appeared to have the greatest effect on each receptor; μ (mu), K (kappa), and δ (delta) [10]. The mu opioid receptor is primarily re- sponsible for analgesia and the rewarding effects that can lead to https://doi.org/10.1016/j.jns.2020.116728 Received 8 August 2019; Received in revised form 15 January 2020; Accepted 6 February 2020 Abbreviations: CD, chemical dependency; CBT, cognitive behavioral therapy; DSM–5, Diagnostic and Statistical Manual of Mental Disorders; FDA, Federal Drug Administration;LDN,low-dosenaltrexone;NIDA,NationalInstituteonDrugAbuse;OUD,opioidusedisorder;SUD,Substanceusedisorders;VTA–NAc,Thenucleus accumbens and ventral tegmental area ⁎ Corresponding author. E-mail address: Oesterle.tyler@mayo.edu (T.S. Oesterle). Journal of the Neurological Sciences 411 (2020) 116728 Available online 11 February 2020 0022-510X/ © 2020 Elsevier B.V. All rights reserved. T