Editing Oxycodone (section)

==History==
[[Martin Freund]] and (Jakob) [[Edmund Speyer]] of the [[Johann Wolfgang Goethe University Frankfurt am Main|University of Frankfurt]] in Germany published the first synthesis of oxycodone from [[thebaine]] in 1916.<ref>{{cite journal | vauthors = Freund M, Speyer E |title=Über die Umwandlung von Thebain in Oxycodeinon und dessen Derivate |journal=Journal für Praktische Chemie |date=24 November 1916 |volume=94 |issue=1 |pages=135–178 |doi=10.1002/prac.19160940112 |url=https://zenodo.org/record/1428060 }}</ref><ref name="Oxysynthesis2005">{{cite book |url=https://archive.org/details/drugdiscoveryhis00snea |title=Drug discovery: a history |vauthors=Sneader W |publisher=Wiley |year=2005 |isbn=978-0-471-89980-8 |location=Hoboken, NJ |page=[https://archive.org/details/drugdiscoveryhis00snea/page/n132 119] |url-access=limited}}</ref> When Freund died, in 1920, Speyer wrote his obituary for the [[German Chemical Society]].<ref>{{cite journal |title=Martin Freund |journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series) |date=7 May 1921 |volume=54 |issue=5 |pages=A53–A79 |doi=10.1002/cber.19210540533}}</ref> Speyer, born to a Jewish family in Frankfurt am Main in 1878, became a victim of the [[Holocaust]]. He died on 5 May 1942, the second day of deportations from the [[Lodz Ghetto]]; his death was noted in the ghetto's chronicle.<ref>{{cite book |title=The Holocaust: a history of the Jews of Europe during the Second World War |year=1986 |url=https://archive.org/details/holocausthistory0000gilb |url-access=registration |publisher=Holt, Rinehart, and Winston |isbn=0-03-062416-9 |pages=[https://archive.org/details/holocausthistory0000gilb/page/346 346] |edition=1st American |access-date=3 June 2020}}</ref>

The first clinical use of the drug was documented in 1917, the year after it was first developed.<ref name=Oxysynthesis2005/><ref name="sunshine1996"/> It was first introduced to the U.S. market in May 1939. In early 1928, [[Merck Group|Merck]] introduced a combination product containing [[Hyoscine hydrobromide|scopolamine]], oxycodone, and [[ephedrine]] under the German initials for the ingredients SEE, which was later renamed Scophedal (SCOpolamine, ePHEDrine, and eukodAL) in 1942. It was last manufactured in 1987 but can be [[Compounded drug|compounded]]. This combination is essentially an oxycodone [[Analogue (chemical)|analogue]] of the morphine-based "[[twilight sleep]]", with ephedrine added to reduce circulatory and respiratory effects.<ref name="ReferenceA">{{cite journal | vauthors = Defalque RJ, Wright AJ | title = Scophedal (SEE) was it a fad or a miracle drug? | journal = Bulletin of Anesthesia History | volume = 21 | issue = 4 | pages = 12–14 | date = October 2003 | pmid = 17494237 | doi = 10.1016/S1522-8649(03)50051-8 }}</ref> The drug became known as the "Miracle Drug of the 1930s" in Continental Europe and elsewhere and it was the [[Wehrmacht]]'s choice for a battlefield analgesic for a time. The drug was expressly designed to provide what the patent application and package insert referred to as "very deep analgesia and profound and intense euphoria" as well as tranquillisation and [[anterograde amnesia]] useful for surgery and battlefield wounding cases. Oxycodone was allegedly chosen over other common opiates for this product because it had been shown to produce less sedation at equianalgesic doses compared to morphine, hydromorphone (Dilaudid), and hydrocodone (Dicodid).<ref>William S Burroughs 1952 letter to Allen Ginsburg concerning Eukodal, in Collected Correspondance, pp 141–2</ref>

During [[Operation Himmler]], Skophedal was also reportedly injected in massive overdose into the prisoners dressed in Polish Army uniforms in the [[Gleiwitz incident|staged incident on 1 September 1939]] which opened the Second World War.<ref name="ReferenceA"/><ref>Merck 1930 package insert for Skophedal (German)</ref>

The personal notes of [[Adolf Hitler]]'s physician, [[Theodor Morell]], indicate Hitler received repeated injections of "Eukodal" (oxycodone; produced by Merck) and Scophedal, as well as Dolantin ([[pethidine]]) codeine, and [[morphine]] less frequently; oxycodone could not be obtained after late January 1945.<ref>{{Cite web |url= http://www.dw.com/en/a-fresh-light-on-the-nazis-wartime-drug-addiction/a-18703678 |title=A fresh light on the Nazis' wartime drug addiction |vauthors= Breitenbach D |date=9 September 2015 |website=Deutsche Welle |location=Bonn |access-date=24 April 2016 |archive-date=25 April 2016 |archive-url= https://web.archive.org/web/20160425040250/http://www.dw.com/en/a-fresh-light-on-the-nazis-wartime-drug-addiction/a-18703678 |url-status=live }}</ref><ref>{{cite book | vauthors = Ohler N, Whiteside S |title=Blitzed: drugs in the Third Reich |year=2017 |publisher=Houghton Mifflin Harcourt |location=Boston |isbn=978-1-328-66379-5 |edition=First U.S. |page = 194 }}</ref>

In the United States, the [[Controlled Substances Act|Controlled Substances Act (CSA)]] was passed by the United States Congress and signed into law by President [[Richard Nixon]] on 27 October 1970.<ref>{{USStatute|91|513|84|1236|1970|10|27}}, codified at {{usc|21|801}}et. seq.</ref> The passing of the CSA resulted in all products containing oxycodone being classified as a [[Schedule II Controlled Substance|Schedule II controlled substance]].<ref>{{Cite journal | vauthors = Sapienza FL |date= June 2006 |title=Abuse deterrent formulations and the Controlled Substances Act (CSA) |url=https://www.sciencedirect.com/science/article/pii/S0376871606000561 |journal=Drug and Alcohol Dependence |series=Drug Formulation and Abuse Liability |volume=83 |pages=S23–S30 |doi=10.1016/j.drugalcdep.2005.11.028 |pmid=16529882 |issn=0376-8716 |quote=The CSA as enacted in 1970 provides examples of specifically listed substances in one schedule and formulations containing them in different schedules. The CSA also provides a mechanism to exempt certain formulations and products from regulations. ... Each of these substances is in Schedule II of the CSA. However, formulations/products containing limited amounts of these substances in combination with an isoquinoline alkaloid or one or more active non-narcotic ingredients in recognized therapeutic amounts were included in Schedule III or V of the CSA (Public Law 91-513, Section 202). ... It is interesting to note that no criteria were established for the differential control of the Schedule II opioid oxycodone and its combination products. Thus, oxycodone and all marketed single entity and combination products are in Schedule II.}}</ref><!-- Oxycodone is not listed by name in the CSA of 1970: https://www.govinfo.gov/content/pkg/STATUTE-84/pdf/STATUTE-84-Pg1236.pdf. Either a medical or legal source is needed to explain how and when it was scheduled. -->

[[Purdue Pharma]], a privately held company based in Stamford, Connecticut, developed the prescription painkiller OxyContin. It was approved by the FDA in 1995 after no long-term studies and no assessment of its addictive capabilities.<ref>{{cite web |title=Confirmation Hearing for FDA Commissioner Nominee |date=14 December 2021 |url= https://archive.org/details/CSPAN3_20211214_150000_Confirmation_Hearing_for_FDA_Commissioner_Nominee |publisher=[[C-SPAN]] |access-date=12 December 2022}}</ref> David Kessler, the [[Commissioner of Food and Drugs|FDA commissioner]] at the time, later said of the approval of OxyContin: "No doubt it was a mistake. It was certainly one of the worst medical mistakes, a major mistake."<ref>{{cite news | vauthors = Mitchell J |title=How the FDA helped pave the way for an opioid epidemic |url= https://www.clarionledger.com/story/news/2018/01/26/opioid-epidemic-how-fda-helped-pave-way/950561001/ |access-date=12 December 2022 |work= Clarion Ledger |location= Jackson MS |date=26 January 2018}}</ref> Upon its release in 1995, OxyContin was hailed as a medical breakthrough, a long-lasting narcotic that could help patients with moderate to severe pain. The drug became a blockbuster and has reportedly generated some US$35 billion in revenue for Purdue.<ref name="eop">{{cite magazine |url=https://www.newyorker.com/magazine/2017/10/30/the-family-that-built-an-empire-of-pain |title=The Family That Built an Empire of Pain |vauthors= Keefe PR |author-link=Patrick Radden Keefe |date=23 October 2017 |magazine=[[The New Yorker]] |access-date=2 February 2019 |archive-date=22 January 2018 |archive-url= https://web.archive.org/web/20180122073308/https://www.newyorker.com/magazine/2017/10/30/the-family-that-built-an-empire-of-pain |url-status=live }}</ref>