Editing Thebaine

{{Short description|Opiate alkaloid constituent of opium}}
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477174254
| ImageFile = Thebaine skeletal.svg
| ImageClass = skin-invert-image
| ImageSize = 190
| ImageName = Skeletal formula
| ImageFile2 = Thebaine molecule ball.png
| ImageSize2 = 210
| ImageName2 = Ball-and-stick model
| IUPACName = 3,6-Dimethoxy-17-methyl-6,7,8,14-tetradehydro-4,5α-epoxymorphinan
| SystematicName = (4''R'',7a''R'',12b''S'')-7,9-Dimethoxy-3-methyl-2,3,4,7a-tetrahydro-1''H''-4,12-methano[1]benzofuro[3,2-''e'']isoquinoline
| OtherNames = Paramorphine
|Section1={{Chembox Identifiers
| Abbreviations = 
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 2P9MKG8GX7
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 403893
| InChI = 1S/C19H21NO3/c1-20-9-8-19-12-5-7-15(22-3)18(19)23-17-14(21-2)6-4-11(16(17)19)10-13(12)20/h4-7,13,18H,8-10H2,1-3H3/t13-,18+,19+/m1/s1
| InChIKey = FQXXSQDCDRQNQE-VMDGZTHMBG
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C19H21NO3/c1-20-9-8-19-12-5-7-15(22-3)18(19)23-17-14(21-2)6-4-11(16(17)19)10-13(12)20/h4-7,13,18H,8-10H2,1-3H3/t13-,18+,19+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FQXXSQDCDRQNQE-VMDGZTHMSA-N
| InChIKey1 = FQXXSQDCDRQNQE-VMDGZTHMSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 115-37-7
| ChemSpiderID = 4481822
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID1_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID1 = 4479543
| EINECS = 
| PubChem = 5324289
| SMILES = COC1=CC=C2[C@@H](C3)N(C)CC[C@@]24C5=C3C=CC(OC)=C5O[C@@H]14
| RTECS =
| MeSHName = Thebaine
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 9519
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = C06173
}}
|Section2={{Chembox Properties
| Formula =
| C=19 | H=21 | N=1 | O=3
| MolarMass = 311.37 g/mol
| Appearance =
| Density = 
| MeltingPt = 
| MeltingPt_notes =
| BoilingPt = 
| BoilingPt_notes = 
| Solubility = 
| SolubleOther = 
| Solvent = 
| pKa = 
| pKb = }}
|Section3={{Chembox Pharmacology
| ProteinBound = 
| Bioavail = 
| Metabolism = ''O''-demethylation<ref name="mikus1991">{{cite journal |author1=Mikus, G. |author2=Somogyi, A. A. |author3=Bochner, F. |author4=Eichelbaum, M. | title = Thebaine O-demethylation to oripavine: Genetic differences between two rat strains | journal = Xenobiotica | year = 1991 | volume = 21 | issue = 11 | pages = 1501–9 | pmid = 1763524 | doi=10.3109/00498259109044400}}</ref>
| HalfLife = 
| Excretion = 
| Pregnancy_category = 
| Pregnancy_AU = 
| Legal_AU = S8
| Legal_BR = A1
| Legal_CA = Schedule I
| Legal_UK = Class A
| Legal_US = Schedule II
| Legal_status = 
| AdminRoutes = 
| Licence_EU = 
| Licence_US =
| Dependence_liability = Low<ref name="who1980">{{ cite journal | author = WHO Advisory Group | title = The dependence potential of thebaine | journal = Bulletin on Narcotics | year = 1980 | volume = 32 | issue = 1 | pages = 45–54 | pmid = 6778542 | url = https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1980-01-01_1_page006.html | url-status = live | archive-url = https://web.archive.org/web/20140512225626/https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1980-01-01_1_page006.html | archive-date = 2014-05-12 }}</ref>}}
}}
'''Thebaine''' ('''paramorphine'''), also known as '''codeine methyl enol ether''', is an [[opiate]] [[alkaloid]], its name coming from the [[Greek language|Greek]] Θῆβαι, ''[[Thebes, Egypt|Thēbai]]'' (Thebes), an ancient city in [[Upper Egypt]]. A minor constituent of [[opium]], thebaine is chemically similar to both [[morphine]] and [[codeine]], but has stimulatory rather than depressant effects.  At high doses, it causes convulsions similar to [[strychnine]] poisoning. The synthetic [[enantiomer]] (+)-thebaine does show analgesic effects apparently mediated through opioid receptors, unlike the inactive natural enantiomer (−)-thebaine.<ref name="aceto 1999">{{cite journal |author1=Aceto, M. D. |author2=Harris, L. S. |author3=Abood, M. E. |author4=Rice, K. C. | title = Stereoselective μ- and δ-opioid receptor-related antinociception and binding with (+)-thebaine | journal = European Journal of Pharmacology | year = 1999 | volume = 365 | issue = 2–3 | pages = 143–7 | pmid = 9988096 | doi = 10.1016/S0014-2999(98)00862-0 }}</ref> While thebaine is not used therapeutically, it is the main alkaloid extracted from ''[[Papaver bracteatum]]'' (Iranian opium / Persian poppy) and can be converted industrially into a variety of compounds, including [[hydrocodone]], [[hydromorphone]], [[oxycodone]], [[oxymorphone]], [[nalbuphine]], [[naloxone]], [[naltrexone]], [[buprenorphine]], [[butorphanol]] and [[etorphine]].<ref>{{cite web |url=http://www.deadiversion.usdoj.gov/schedules/orangebook/a_sched_alpha.pdf |title=DEA Diversion Control Division |access-date=2014-07-12 |url-status=live |archive-url=https://web.archive.org/web/20140611095921/http://www.deadiversion.usdoj.gov/schedules/orangebook/a_sched_alpha.pdf |archive-date=2014-06-11 }}</ref>

Thebaine is controlled under international law, is listed as a Class A drug under the [[Misuse of Drugs Act 1971]] in the United Kingdom, is controlled as an analog of a Schedule II drug per the [[Analog Act]] in the United States, and is controlled with its derivatives and salts, as a Schedule I substance of the [[Controlled Drugs and Substances Act]] in Canada.<ref>{{ cite web | url = http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-24.html#h-28 | title = Controlled Drugs and Substances Act | publisher = Government of Canada | work = Justice Laws Website | date = 2012-11-06 | access-date = 2014-01-12 | url-status = dead | archive-url = https://web.archive.org/web/20131122143804/http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-24.html#h-28 | archive-date = 2013-11-22 }}</ref>  The 2013 US [[Drug Enforcement Administration]] (DEA) aggregate manufacturing quota for thebaine (ACSCN 9333) was unchanged from the previous year at 145 metric tons.

This alkaloid is biosynthetically related to [[salutaridine]], [[oripavine]], [[morphine]] and [[reticuline]].<ref>{{cite journal | last1 = Novak | first1 = B. | last2 = Hudlicky | first2 = T. | last3 = Reed | first3 = J. | last4 = Mulzer | first4 = J. | last5 = Trauner | first5 = D. | title = Morphine Synthesis and Biosynthesis-An Update | journal = Current Organic Chemistry | year = 2000 | volume = 4 | issue = 3 | pages = 343–62 | doi = 10.2174/1385272003376292 | url = http://brocku.ca/mathematics-science/departments-and-centres/chemistry/faculty/Hudlicky/CurrOrgChem-2000-4-343.pdf | url-status = live | archive-url = https://web.archive.org/web/20120619063224/http://brocku.ca/mathematics-science/departments-and-centres/chemistry/faculty/Hudlicky/CurrOrgChem-2000-4-343.pdf | archive-date = 2012-06-19 | citeseerx = 10.1.1.515.9096 }}</ref>

In 2012 there was an amounted 146,000 kilograms of thebaine produced.<ref name=UN2015>{{cite book|title=Narcotic Drugs 2014|date=2015|publisher=INTERNATIONAL NARCOTICS CONTROL BOARD|isbn=9789210481571|page=21|url=https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf|url-status=live|archive-url=https://web.archive.org/web/20150602192211/https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf|archive-date=2015-06-02}}</ref> In 2013, Australia was the main producer of [[poppy straw]] rich in thebaine, followed by Spain and then France. By 2017, worldwide thebaine production dropped to 2,008 kg.<ref>{{Cite web|date=|title=International Narcotics Control Board Narcotic Drugs 2018|url=https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2018/INCB-Narcotics_Drugs_Technical_Publication_2018.pdf|access-date=|website=INCB.org}}</ref> Together, those three countries accounted for about 99 per cent of global production of such poppy straw. The [[Papaver bracteatum]] seed capsules are the primary source of thebaine, with the stem additionally yielding a significant amount.<ref>{{Cite web|url = https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf|title = Narcotic Drugs: Estimated World Requirements for 2015; Statistics for 2013|date = 2015|access-date = January 7, 2016|website = International Narcotics Control Board|publisher = United Nations International Narcotics Control Board|page = 151 ff|url-status = live|archive-url = https://web.archive.org/web/20150602192211/https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf|archive-date = June 2, 2015}}</ref><ref>{{cite news |last1=Whoriskey |first1=Peter |title=Johnson & Johnson companies used a super poppy to make narcotics for popular opioid pills - Washington Post |url=https://www.washingtonpost.com/graphics/2020/business/opioid-crisis-johnson-and-johnson-tasmania-poppy/?itid=hp_ed-picks_poppy-0326%3Ahomepage%2Fstory-ans |newspaper=Washington Post |access-date=27 March 2020}}</ref>

[[The Canberra Times]] of 16 November 2022<ref>{{cite web |url=https://www.canberratimes.com.au/story/7982992/urgent-recall-hoyts-poppy-seeds-linked-to-poisoning-cardiac-arrest/ |title=DEA Diversion Control Division |access-date=2014-07-12 |url-status=live |archive-url=https://web.archive.org/web/20140611095921/http://www.deadiversion.usdoj.gov/schedules/orangebook/a_sched_alpha.pdf |archive-date=2014-06-11 }}</ref> reported that four batches of Hoyts brand [[poppy seeds]] were being recalled due to unusually high levels of thebaine, and that at least twelve people in [[New South Wales]] had required medical attention after ingesting them. As of 15 November 2022, [[Food Standards Australia New Zealand]] (FSANZ) is coordinating a national recall of a number of poppy seed products due to the potential presence of thebaine.<ref>{{cite web |title=National Recall of Poppy Seeds |url=https://www.foodstandards.gov.au/industry/foodrecalls/recalls/nationalrecallpoppyseeds/Pages/National-Recall-of-Poppy-Seeds.aspx |website=Food Standards Australia New Zealand |publisher=Food Standards Australia New Zealand (FSANZ) |access-date=21 November 2022}}</ref>

==Synthesis==

===Research===
Thebaine has been produced by [[GMO]] [[E. coli]].<ref>{{cite web |title=Genetically modified E. coli pump out morphine precursor: Bacteria yield 300 times more opiates than yeast |url=https://www.sciencedaily.com/releases/2016/02/160225101103.htm |website=ScienceDaily |language=en}}</ref>

==See also==
* [[Thebacon]]
* [[6,14-Endoethenotetrahydrooripavine]] - the central nucleus of the [[Bentley compounds|Bentley compound]] class of opioids which are derived from thebaine

==References==
{{Reflist}}

{{Components of Opium}}
{{Glycinergics}}
{{Opioidergics}}
{{Convulsants}}
{{Authority control}}

[[Category:4,5-Epoxymorphinans]]
[[Category:Ethers]]
[[Category:Natural opium alkaloids]]
[[Category:Cyclohexadienes]]
[[Category:Glycine receptor antagonists]]
[[Category:Opiates]]
[[Category:Convulsants]]
[[Category:Enol ethers]]