View source for Morphine

{{Short description|Pain medication of the opiate family}}
{{Distinguish|Morpheein|Morpheme}}
{{Redirect|Morphia|the queen of Jerusalem|Morphia of Melitene}}
{{Use dmy dates|date=September 2024}}
{{Use American English|date=February 2018}}
{{Cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| verifiedrevid            = 477170110
| image                    = Morphin - Morphine.svg
| width                    = 180
| alt                      = 
| caption                  = 
| image2                   = Morphine molecule ball.png
| alt2                     = 

<!-- Clinical data -->
| pronounce                = {{IPAc-en|ˈ|m|ɔː|r|f|iː|n}}
| tradename                = Statex, MS Contin, Oramorph, others<ref name="drugs.com-page" />
| Drugs.com                = {{drugs.com|monograph|morphine}}
| MedlinePlus              = a682133
| DailyMedID               = Morphine
| pregnancy_AU             = C
| pregnancy_AU_comment     = <ref name="Drugs.com pregnancy">{{cite web | title=Morphine Use During Pregnancy | website=Drugs.com | date=14 October 2019 | url=https://www.drugs.com/pregnancy/morphine.html | access-date=21 August 2020}}</ref>
| pregnancy_category       = 
| dependency_liability     = High
| addiction_liability      = High<ref>{{cite book | vauthors = Bonewit-West K, Hunt SA, Applegate E |title=Today's Medical Assistant: Clinical and Administrative Procedures |date=2012|page=571 |publisher=Elsevier Health Sciences |isbn=978-1-4557-0150-6 |url=https://books.google.com/books?id=YalYPI1KqTQC&pg=PA571 }}</ref>
| routes_of_administration = [[Inhalation]], [[Insufflation (medicine)|insufflation]], [[oral administration|by mouth]], [[Rectal administration|rectal]], [[Subcutaneous injection|subcutaneous]], [[intramuscular]], [[intravenous]], [[epidural]], [[intrathecal]]
| class                    = [[Opiate]]
| ATC_prefix               = N02
| ATC_suffix               = AA01
| ATC_supplemental         = 

<!-- Legal status -->
| legal_AU                 = S8
| legal_AU_comment         = 
| legal_BR                 = A1
| legal_BR_comment         = 
| legal_CA                 = Schedule I
| legal_CA_comment         = <ref>{{cite web | title=Morphine Product information | website=[[Health Canada]]| date=9 August 2005 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=3042 | access-date=4 April 2024}}</ref>
| legal_DE                 = Anlage III
| legal_DE_comment         = 
| legal_NZ                 = Class B
| legal_NZ_comment         = 
| legal_UK                 = POM
| legal_UK_comment         = /{{nbsp}}Class A<ref name="Black's"/><ref>{{cite web | title=Sevredol Summary of Product Characteristics (SmPC) | website=(emc) | date=13 February 2024 | url=https://www.medicines.org.uk/emc/product/1020/smpc | access-date=20 February 2024}}</ref>
| legal_US                 = Schedule II
| legal_US_comment         = /{{nbsp}}Schedule III<ref>{{cite web | title=MS Contin- morphine sulfate tablet | website=DailyMed | date=27 December 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c354b3bf-86c0-4bb8-8b1f-be2164942698 | access-date=20 February 2024}}</ref>
| legal_EU                 = Rx-only
| legal_EU_comment         = <ref>{{cite web | title=Modified-released oral opioids | website=European Medicines Agency | date=18 November 2010 | url=https://www.ema.europa.eu/en/medicines/human/referrals/modified-released-oral-opioids | access-date=20 February 2024}}</ref>
| legal_UN                 = N I III
| legal_UN_comment         = 
| legal_status             = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability          = 20{{ndash}}40% (by mouth), 36{{ndash}}71% (rectal),<ref name="pmid3387374">{{cite journal | vauthors = Jonsson T, Christensen CB, Jordening H, Frølund C | title = The bioavailability of rectally administered morphine | journal = Pharmacology & Toxicology | volume = 62 | issue = 4 | pages = 203–5 | date = April 1988 | pmid = 3387374 | doi = 10.1111/j.1600-0773.1988.tb01872.x }}</ref> 100% (IV/IM)
| protein_bound            = 30{{ndash}}40%
| metabolism               = [[Liver]]: [[UGT2B7]]
| metabolites              = • [[Morphine-3-glucuronide]] (90%)<br />• [[Morphine-6-glucuronide]] (10%)
| onset                    = 5&nbsp;minutes (IV), 15&nbsp;minutes (IM),<ref>{{cite book | vauthors = Whimster F |title = Cambridge textbook of accident and emergency medicine |date = 1997 |publisher = Cambridge University Press |location = Cambridge |isbn = 978-0-521-43379-2 |page = 191 |url = https://books.google.com/books?id=m0bNaDhkaukC&pg=PA191 |url-status = live |archive-url = https://web.archive.org/web/20170908135509/https://books.google.com/books?id=m0bNaDhkaukC&pg=PA191 |archive-date = 8 September 2017 }}</ref> 20&nbsp;minutes (PO)<ref>{{cite book | vauthors = Liben S |title = Oxford textbook of palliative care for children |date = 2012 |publisher = Oxford University Press |location = Oxford |isbn = 978-0-19-959510-5 |page = 240 |edition = 2 |url = https://books.google.com/books?id=k3XNeNseoHIC&pg=PA240 |url-status = live |archive-url = https://web.archive.org/web/20170908135509/https://books.google.com/books?id=k3XNeNseoHIC&pg=PA240 |archive-date = 8 September 2017 }}</ref>
| elimination_half-life    = 2{{ndash}}3&nbsp;hours
| duration_of_action       = 3{{ndash}}7&nbsp;hours<ref name=AHFS2015 /><ref name=Rockwood2009 />
| excretion                = [[Kidney]] 90%, [[bile duct]] 10%

<!-- Identifiers -->
| CAS_number_Ref           = {{cascite|correct|??}}
| CAS_number               = 57-27-2
| CAS_supplemental         = <br />64-31-3 (neutral sulfate),<br />52-26-6 (hydrochloride)
| PubChem                  = 5288826
| IUPHAR_ligand            = 1627
| DrugBank_Ref             = {{drugbankcite|correct|drugbank}}
| DrugBank                 = DB00295
| ChemSpiderID_Ref         = {{chemspidercite|correct|chemspider}}
| ChemSpiderID             = 4450907
| UNII_Ref                 = {{fdacite|correct|FDA}}
| UNII                     = 76I7G6D29C
| KEGG_Ref                 = {{keggcite|correct|kegg}}
| KEGG                     = D08233
| ChEBI_Ref                = {{ebicite|correct|EBI}}
| ChEBI                    = 17303
| ChEMBL_Ref               = {{ebicite|correct|EBI}}
| ChEMBL                   = 70
| NIAID_ChemDB             = 
| PDB_ligand               = MOI
| synonyms                 = 

<!-- Chemical and physical data -->
| IUPAC_name               = (4''R'',4a''R'',7''S'',7a''R'',12b''S'')-3-Methyl-2,3,4,4a,7,7a-hexahydro-1''H''-4,12-methano[1]benzofuro[3,2-''e'']isoquinoline-7,9-diol
| C                        = 17
| H                        = 19
| N                        = 1
| O                        = 3
| SMILES                   = CN1CC[C@]23C4=C5C=CC(O)=C4O[C@H]2[C@@H](O)C=C[C@H]3[C@H]1C5
| StdInChI_Ref             = {{stdinchicite|correct|chemspider}}
| StdInChI                 = 1S/C17H19NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2-5,10-11,13,16,19-20H,6-8H2,1H3/t10-,11+,13-,16-,17-/m0/s1
| StdInChI_comment         = 
| StdInChIKey_Ref          = {{stdinchicite|correct|chemspider}}
| StdInChIKey              = BQJCRHHNABKAKU-KBQPJGBKSA-N
| density                  = 
| density_notes            = 
| melting_point            = 
| melting_high             = 
| melting_notes            = 
| boiling_point            = 
| boiling_notes            = 
| solubility               = HCl & sulf.: 60
| sol_units                = 
| specific_rotation        = 
}}

'''Morphine''', formerly also called '''morphia''',<ref name="Morphia">{{cite web |title=Morphia |url=https://www.lexico.com/en/definition/morphia |archive-url=https://web.archive.org/web/20200804021300/https://www.lexico.com/en/definition/morphia |url-status=dead |archive-date=4 August 2020 |website=Lexico Dictionaries {{!}} English |access-date=14 September 2019 }}</ref> is an [[opiate]] that is found naturally in [[opium]], a dark brown resin produced by drying the latex of opium poppies (''[[Papaver somniferum]]''). It is mainly used as an [[analgesic]] (pain medication). There are numerous methods used to administer morphine: oral; [[sublingual administration|sublingual]]; via inhalation; [[intramuscular|injection into a muscle]], [[Subcutaneous injection|injection under the skin]], or injection into the [[spinal cord]] area; [[transdermal]]; or via [[rectal administration|rectal]] [[suppository]].<ref name="AHFS2015" /><ref name="St2012">{{cite journal | vauthors = Stefano GB, Ptáček R, Kuželová H, Kream RM | title = Endogenous morphine: up-to-date review 2011 | journal = Folia Biologica | volume = 58 | issue = 2 | pages = 49–56 | date = 2012 | doi = 10.14712/fb2012058020049 | pmid = 22578954 | url = http://fb.cuni.cz/file/5635/FB2012A0008.pdf | url-status = dead | quote = Positive evolutionary pressure has apparently preserved the ability to synthesize chemically authentic morphine, albeit in homeopathic concentrations, throughout animal phyla. | archive-url = https://web.archive.org/web/20160824130751/http://fb.cuni.cz/file/5635/FB2012A0008.pdf | archive-date = 24 August 2016 | access-date = 10 October 2016 }}</ref> It acts directly on the [[central nervous system]] (CNS) to induce [[analgesia]] and alter perception and emotional response to pain. Physical and psychological dependence and tolerance may develop with repeated administration.<ref name="AHFS2015" /> It can be taken for both [[acute pain]] and [[chronic pain]] and is frequently used for pain from [[myocardial infarction]], [[kidney stone]]s, and during [[Childbirth|labor]].<ref name="AHFS2015" /> Its maximum effect is reached after about 20&nbsp;minutes when administered intravenously and 60&nbsp;minutes when administered by mouth, while the duration of its effect is 3–7&nbsp;hours.<ref name="AHFS2015" /><ref name="Rockwood2009">{{cite book | vauthors = Rockwood CA |title = Rockwood and Wilkins' fractures in children |date = 2009 |publisher = Lippincott Williams & Wilkins |location = Philadelphia, Pa. |isbn = 978-1-58255-784-7 |page = 54 |edition = 7th |url = https://books.google.com/books?id=QVIdXV_F8M4C&pg=PA54 |url-status = live |archive-url = https://web.archive.org/web/20170908135509/https://books.google.com/books?id=QVIdXV_F8M4C&pg=PA54 |archive-date = 8 September 2017 }}</ref> [[Extended-release morphine|Long-acting formulations of morphine]] are sold under the brand names '''MS Contin''' and '''Kadian''', among others. Generic long-acting formulations are also available.<ref name="AHFS2015">{{cite web |title = Morphine sulfate |url = https://www.drugs.com/monograph/morphine-sulfate.html |publisher = The American Society of Health-System Pharmacists |access-date = 1 June 2015 |url-status = live |archive-url = https://web.archive.org/web/20150502143444/http://www.drugs.com/monograph/morphine-sulfate.html |archive-date = 2 May 2015 }}</ref>

Common side effects of morphine include [[drowsiness]], [[euphoria]], [[nausea]], [[dizziness]], [[sweating]], and [[constipation]].<ref name="AHFS2015" /> Potentially serious [[side effects]] of morphine include [[Hypoventilation|decreased respiratory effort]], [[vomiting]], and [[low blood pressure]].<ref name=AHFS2015 /> Morphine is highly [[addiction|addictive]] and prone to [[substance abuse|abuse]].<ref name=AHFS2015 /> If one's dose is reduced after long-term use, [[opioid withdrawal]] symptoms may occur.<ref name=AHFS2015 /> Caution is advised for use of morphine during [[pregnancy]] or [[breast feeding]], as it may affect the health of the baby.<ref name=AHFS2015 /><ref name="Drugs.com pregnancy" />

Morphine was first isolated in 1804 by German pharmacist [[Friedrich Sertürner]].<ref name="pmid18443637">{{cite journal | vauthors = Trescot AM, Datta S, Lee M, Hansen, H | title = Opioid Pharmacology | journal = Pain Physician Journal | volume = 11 | issue = 2 | pages = S133-53 | date = March 2008 | doi = 10.36076/ppj.2008/11/S133 | pmid = 18443637 }}</ref><ref name=Court2009>{{cite book | vauthors = Courtwright DT |title = Forces of habit drugs and the making of the modern world |date = 2009 |publisher = Harvard University Press |location = Cambridge, Mass. |isbn = 978-0-674-02990-3 |pages = 36–37 |edition = 1 |url = https://books.google.com/books?id=GHqV3elHYvMC&pg=PA36 |url-status = live |archive-url = https://web.archive.org/web/20170908135509/https://books.google.com/books?id=GHqV3elHYvMC&pg=PA36 |archive-date = 8 September 2017 }}</ref> This is believed to be the first isolation of a medicinal alkaloid from a plant.<ref name=Luch2009>{{cite book |url = https://books.google.com/books?id=MtOiLVWBn8cC&pg=PA20 |page = 20 |title = Molecular, clinical and environmental toxicology | veditors = Luch A |publisher = Springer |year = 2009 |isbn = 978-3-7643-8335-0 }}</ref> [[Merck Group|Merck]] began marketing it commercially in 1827.<ref name=Court2009 /> Morphine was more widely used after the invention of the [[hypodermic syringe]] in 1853{{ndash}}1855.<ref name=Court2009 /><ref name=Clay2013 /> Sertürner originally named the substance ''morphium'', after the Greek god of dreams, [[Morpheus (mythology)|Morpheus]], as it has a tendency to cause sleep.<ref name=Clay2013>{{cite book | vauthors = Mosher CJ |title = Drugs and Drug Policy: The Control of Consciousness Alteration |date = 2013 |publisher = SAGE Publications |isbn = 978-1-4833-2188-2 |page = 123 |url = https://books.google.com/books?id=2UQXBAAAQBAJ&pg=PA123 |url-status = live |archive-url = https://web.archive.org/web/20170908135509/https://books.google.com/books?id=2UQXBAAAQBAJ&pg=PA123 |archive-date = 8 September 2017 }}</ref><ref>{{cite book | vauthors = Fisher GL |title = Encyclopedia of substance abuse prevention, treatment, & recovery |date = 2009 |publisher = SAGE |location = Los Angeles |isbn = 978-1-4522-6601-5 |page = 564 |url = https://books.google.com/books?id=DFR2AwAAQBAJ&pg=PT598 |url-status = live |archive-url = https://web.archive.org/web/20170908135509/https://books.google.com/books?id=DFR2AwAAQBAJ&pg=PT598 |archive-date = 8 September 2017 }}</ref>

The primary source of morphine is isolation from [[poppy straw]] of the [[Papaver somniferum|opium poppy]].<ref>{{cite book |title = Narcotic Drugs Estimated World Requirements for 2008, Statistics for 2006 |date = 2008 |publisher = United Nations Pubns |location = New York |isbn = 978-92-1-048119-9 |page = 77 |url = https://books.google.com/books?id=0_9QHvacPzYC&pg=PA77 |url-status = live |archive-url = https://web.archive.org/web/20170908135509/https://books.google.com/books?id=0_9QHvacPzYC&pg=PA77 |archive-date = 8 September 2017 }}</ref> In 2013, approximately 523 tons of morphine were produced.<ref name=UN2015 /> Approximately 45 tons were used directly for pain, an increase of 400% over the last twenty years.<ref name=UN2015 /> Most use for this purpose was in the [[developed world]].<ref name=UN2015>{{cite book |title = Narcotic Drugs 2014 |date = 2015 |publisher = INTERNATIONAL NARCOTICS CONTROL BOARD |isbn = 978-92-1-048157-1 |pages = 21, 30 |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 = 2 June 2015 }}</ref> About 70% of morphine is used to make other [[opioids]] such as [[hydromorphone]], [[oxymorphone]], and [[heroin]].<ref name=UN2015 /><ref name=Trig2006>{{cite book | vauthors = Triggle DJ |title = Morphine |date = 2006 |publisher = Chelsea House Publishers |location = New York |isbn = 978-1-4381-0211-5 |pages = 20–21 |url = https://books.google.com/books?id=sud4ORAMNkYC&pg=PA20 }}</ref><ref name=Kar2006>{{cite book | vauthors = Karch SB |title = Drug abuse handbook |date = 2006 |publisher = CRC/Taylor & Francis |location = Boca Raton |isbn = 978-1-4200-0346-8 |pages = 7–8 |edition = 2nd |url = https://books.google.com/books?id=F0mUte90ATUC&pg=PA7 }}</ref> It is a [[List of Schedule II drugs (US)|Schedule II drug]] in the United States,<ref name=Trig2006 /> [[Class A drug|Class A]] in the United Kingdom,<ref name="Black's">{{cite book | veditors = Macpherson G |title = Black's Medical Dictionary |series = Nature |volume = 87 |issue = 2184 |date = 2002 |isbn = 978-0-7136-5442-4 |page = 162 |edition = 40th |url = https://books.google.com/books?id=bUnCAwAAQBAJ&pg=PA162 |url-status = live |archive-url = https://web.archive.org/web/20170908135509/https://books.google.com/books?id=bUnCAwAAQBAJ&pg=PA162 |archive-date = 8 September 2017 |bibcode = 1911Natur..87R.313. |doi = 10.1038/087313b0 |s2cid = 3979058 }}</ref> and [[Controlled Drugs and Substances Act|Schedule I]] in Canada.<ref>{{cite book |title = Davis's Canadian Drug Guide for Nurses |date = 2014 |publisher = F.A. Davis |isbn = 978-0-8036-4086-3 |page = 1409 |url = https://books.google.com/books?id=0Y8QBAAAQBAJ&pg=PA1409 }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> In 2022, it was the 139th most commonly prescribed medication in the United States, with more than 4{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Morphine Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Morphine | access-date = 30 August 2024 }}</ref> It is available as a [[generic medication]].<ref>{{cite web | title=First Generic Drug Approvals 2023 | website=U.S. [[Food and Drug Administration]] (FDA) | date=30 May 2023 | url=https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals | archive-url=https://web.archive.org/web/20230630003621/https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/first-generic-drug-approvals | archive-date=30 June 2023 | url-status=live | access-date=30 June 2023}}</ref>
{{TOC limit}}

== Medical uses ==
=== Pain ===
Morphine is used primarily to treat both acute and [[chronic pain|chronic]] severe [[pain]]. Its duration of analgesia is about three to seven hours.<ref name=AHFS2015 /><ref name=Rockwood2009 /> Side effects of nausea and constipation are rarely severe enough to warrant stopping treatment.

It is used for pain due to [[myocardial infarction]] and for labor pains.<ref name="AHFS2015" /> However, concerns exist that morphine may increase mortality in the event of [[non ST elevation myocardial infarction]].<ref name="pmid15976786">{{cite journal | vauthors = Meine TJ, Roe MT, Chen AY, Patel MR, Washam JB, Ohman EM, Peacock WF, Pollack CV, Gibler WB, Peterson ED | title = Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative | journal = American Heart Journal | volume = 149 | issue = 6 | pages = 1043–9 | date = June 2005 | pmid = 15976786 | doi = 10.1016/j.ahj.2005.02.010 }}</ref>

Morphine has also traditionally been used in the treatment of [[acute pulmonary edema]].<ref name="AHFS2015" /> However, a 2006 review found little evidence to support this practice.<ref>{{cite web |url = http://www.bestbets.org/bets/bet.php?id=376 |title = BestBets: Does the application of opiates, during an attack of Acute Cardiogenic Pulmonary Oedma, reduce patients' mortality and morbidity? | vauthors = Sosnowski MA |website = BestBets |publisher = Best Evidence Topics |access-date = 6 December 2008 |url-status = live |archive-url = https://web.archive.org/web/20100616155329/http://bestbets.org/bets/bet.php?id=376 |archive-date = 16 June 2010 }}</ref>

A 2016 Cochrane review concluded that morphine is effective in relieving [[cancer pain]].<ref name="Wiffen_2016">{{cite journal | vauthors = Wiffen PJ, Wee B, Moore RA | title = Oral morphine for cancer pain | journal = The Cochrane Database of Systematic Reviews | volume = 4 | pages = CD003868 | date = April 2016 | issue = 3 | pmid = 27105021 | pmc = 6540940 | doi = 10.1002/14651858.CD003868.pub4 }}</ref>

=== Shortness of breath ===
Morphine is beneficial in reducing the symptom of [[shortness of breath]] due to both [[cancer]] and non-cancer causes.<ref name=Pal2010>{{cite journal | vauthors = Schrijvers D, van Fraeyenhove F | title = Emergencies in palliative care | journal = Cancer Journal | volume = 16 | issue = 5 | pages = 514–20 | year = 2010 | pmid = 20890149 | doi = 10.1097/PPO.0b013e3181f28a8d }}</ref><ref>{{cite journal | vauthors = Naqvi F, Cervo F, Fields S | title = Evidence-based review of interventions to improve palliation of pain, dyspnea, depression | journal = Geriatrics | volume = 64 | issue = 8 | pages = 8–10, 12–4 | date = August 2009 | pmid = 20722311 }}</ref> In the setting of breathlessness at rest or on minimal exertion from conditions such as advanced cancer or end-stage cardiorespiratory diseases, regular, low-dose sustained-release morphine significantly reduces breathlessness safely, with its benefits maintained over time.<ref name="pmid22336677">{{cite journal | vauthors = Parshall MB, Schwartzstein RM, Adams L, Banzett RB, Manning HL, Bourbeau J, Calverley PM, Gift AG, Harver A, Lareau SC, Mahler DA, Meek PM, O'Donnell DE | title = An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea | journal = American Journal of Respiratory and Critical Care Medicine | volume = 185 | issue = 4 | pages = 435–52 | date = February 2012 | pmid = 22336677 | pmc = 5448624 | doi = 10.1164/rccm.201111-2042ST }}</ref><ref name="pmid20202949">{{cite journal | vauthors = Mahler DA, Selecky PA, Harrod CG, Benditt JO, Carrieri-Kohlman V, Curtis JR, Manning HL, Mularski RA, Varkey B, Campbell M, Carter ER, Chiong JR, Ely EW, Hansen-Flaschen J, O'Donnell DE, Waller A | title = American College of Chest Physicians consensus statement on the management of dyspnea in patients with advanced lung or heart disease | journal = Chest | volume = 137 | issue = 3 | pages = 674–91 | date = March 2010 | pmid = 20202949 | doi = 10.1378/chest.09-1543 | s2cid = 26739450 | doi-access = free }}</ref>

=== Opioid use disorder ===
Morphine is also available as a slow-release formulation for [[opiate substitution therapy]] (OST) in Austria, Germany, Bulgaria, Slovenia, and Canada for persons with [[opioid addiction]] who cannot tolerate either [[methadone]] or [[buprenorphine]].<ref name="NEPOD Report">{{cite book |url = http://www.health.gov.au/internet/drugstrategy/publishing.nsf/Content/8BA50209EE22B9C6CA2575B40013539D/$File/mono52.pdf+ |title = National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD): Report of Results and Recommendation | vauthors = Mattick RP, Digiusto E, Doran C, O'Brien S, Kimber J, Henderson N, Breen B, Shearer J, Gates J, Shakeshaft A | collaboration = NEPOD Trial Investigators |year = 2004 |format = PDF | series = Monograph Series No. 52 |publisher = Australian Government |isbn = 978-0-642-82459-2 |url-status = dead |archive-url = https://web.archive.org/web/20121010081409/http://www.health.gov.au/internet/drugstrategy/publishing.nsf/Content/8BA50209EE22B9C6CA2575B40013539D/$File/mono52.pdf |archive-date = 10 October 2012 }}</ref>

<gallery>
File:GT-Capros-Morphinsulfat-2018.jpg|Two capsules (5&nbsp;mg & 10&nbsp;mg) of morphine sulfate extended-release
File:Morphine 1mL Vial.jpg|1 milliliter ampoule containing 10&nbsp;mg of morphine
</gallery>

== Contraindications ==
Relative [[contraindication]]s to morphine include:
* [[Hypoventilation|respiratory depression]] when appropriate equipment is not available.<ref name=AHFS2015 />
* Although it has previously been thought that morphine was contraindicated in [[acute pancreatitis]], a review of the literature shows no evidence for this.<ref name="pmid11316181">{{cite journal | vauthors = Thompson DR | title = Narcotic analgesic effects on the sphincter of Oddi: a review of the data and therapeutic implications in treating pancreatitis | journal = The American Journal of Gastroenterology | volume = 96 | issue = 4 | pages = 1266–72 | date = April 2001 | doi = 10.1111/j.1572-0241.2001.03536.x | pmid = 11316181 | s2cid = 13209026 }}</ref>

== Adverse effects ==
{{quote box
| title = Adverse effects of opioids|;Common and short term
* [[Itch]]iness<ref name="Furlan">{{cite journal | vauthors = Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E | title = Opioids for chronic noncancer pain: a meta-analysis of effectiveness and side effects | journal = CMAJ | volume = 174 | issue = 11 | pages = 1589–94 | date = May 2006 | pmid = 16717269 | pmc = 1459894 | doi = 10.1503/cmaj.051528 }}</ref>
* [[Nausea]]<ref name="Furlan" />
* [[Vomiting]]<ref name="Furlan" />
* [[Constipation]]<ref name="Furlan" />
* [[Somnolence|Drowsiness]]<ref name="Furlan" />
* [[Xerostomia|Dry mouth]]<ref name="Furlan" />
* [[Respiratory depression]]<ref name=AHFS2015 />
;Other
* [[Opioid dependence]]
* [[Dizziness]]
* Decreased sex drive
* [[Anorexia (symptom)|Loss of appetite]]
* Impaired sexual function
* Decreased testosterone levels
* [[Depression (mood)|Depression]]
* [[Immunodeficiency]]
* [[Opioid-induced hyperalgesia|Opioid-induced abnormal pain sensitivity]]
* [[Irregular menstruation]]
* Increased risk of [[Falling (accident)|falls]]
* Slowed breathing
* [[Hallucinations]]
}}
[[File:MorphineRx.JPG|thumb|A localized reaction to intravenous morphine caused by histamine release in the veins]]
=== Constipation ===
Like [[loperamide]] and other opioids, morphine acts on the [[myenteric plexus]] in the intestinal tract, reducing gut motility, causing constipation. The gastrointestinal effects of morphine are mediated primarily by [[mu Opioid receptor|μ-opioid receptors]] in the bowel. By inhibiting gastric emptying and reducing propulsive [[peristalsis]] of the intestine, morphine decreases the rate of intestinal transit. Reduction in gut secretion and increased intestinal fluid absorption also contribute to the constipating effect. Opioids also may act on the gut indirectly through tonic gut spasms after inhibition of [[nitric oxide]] generation.<ref name="pmid15082884">{{cite journal | vauthors = Stefano GB, Zhu W, Cadet P, Bilfinger TV, Mantione K | title = Morphine enhances nitric oxide release in the mammalian gastrointestinal tract via the micro(3) opiate receptor subtype: a hormonal role for endogenous morphine | journal = Journal of Physiology and Pharmacology | volume = 55 | issue = 1 Pt 2 | pages = 279–88 | date = March 2004 | pmid = 15082884 }}</ref> This effect was shown in animals when a nitric oxide precursor, [[L-arginine]], reversed morphine-induced changes in gut motility.<ref name="Calignano, Moncada and Di Rosa">{{cite journal | vauthors = Calignano A, Moncada S, Di Rosa M | title = Endogenous nitric oxide modulates morphine-induced constipation | journal = Biochemical and Biophysical Research Communications | volume = 181 | issue = 2 | pages = 889–93 | date = December 1991 | pmid = 1755865 | doi = 10.1016/0006-291X(91)91274-G }}</ref>

=== Hormone imbalance ===
{{See also|Opioid#Hormone imbalance}}
Clinical studies consistently conclude that morphine, like other opioids, often causes [[hypogonadism]] and [[hormone imbalance]]s in chronic users of both sexes. This side effect is [[dose–response relationship|dose-dependent]] and occurs in both therapeutic and recreational users. Morphine can interfere with menstruation by suppressing levels of [[luteinizing hormone]]. Many studies suggest the majority (perhaps as many as 90%) of chronic opioid users have opioid-induced hypogonadism. This effect may cause the increased likelihood of [[osteoporosis]] and [[bone fracture]] observed in chronic morphine users. Studies suggest the effect is temporary. {{As of|2013}}, the effect of low-dose or acute use of morphine on the endocrine system is unclear.<ref name="pmid23414717">{{cite journal | vauthors = Brennan MJ | title = The effect of opioid therapy on endocrine function | journal = The American Journal of Medicine | volume = 126 | issue = 3 Suppl 1 | pages = S12-8 | date = March 2013 | pmid = 23414717 | doi = 10.1016/j.amjmed.2012.12.001 }}</ref><ref name="pmid19193821">{{cite journal | vauthors = Colameco S, Coren JS | title = Opioid-induced endocrinopathy | journal = The Journal of the American Osteopathic Association | volume = 109 | issue = 1 | pages = 20–5 | date = January 2009 | pmid = 19193821 }}</ref>

=== Effects on human performance ===
Most reviews conclude that opioids produce minimal impairment of human performance on tests of sensory, motor, or attentional abilities. However, recent studies have been able to show some impairments caused by morphine, which is not surprising, given that morphine is a [[central nervous system]] [[depressant]]. Morphine has resulted in impaired functioning on critical flicker frequency (a measure of overall CNS arousal) and impaired performance on the [[Maddox wing]] test (a measure of the deviation of the visual axes of the eyes). Few studies have investigated the effects of morphine on motor abilities; a high dose of morphine can impair finger tapping and the ability to maintain a low constant level of [[isometric exercise|isometric force]] (i.e. fine motor control is impaired),<ref name="pmid1755931">{{cite journal | vauthors = Kerr B, Hill H, Coda B, Calogero M, Chapman CR, Hunt E, Buffington V, Mackie A | title = Concentration-related effects of morphine on cognition and motor control in human subjects | journal = Neuropsychopharmacology | volume = 5 | issue = 3 | pages = 157–66 | date = November 1991 | pmid = 1755931 }}</ref> though no studies have shown a correlation between morphine and gross motor abilities.

In terms of [[cognitive]] abilities, one study has shown that morphine may have a negative impact on [[anterograde amnesia|anterograde]] and [[retrograde amnesia|retrograde memory]],<ref>{{cite journal | vauthors = Friswell J, Phillips C, Holding J, Morgan CJ, Brandner B, Curran HV | title = Acute effects of opioids on memory functions of healthy men and women | journal = Psychopharmacology | volume = 198 | issue = 2 | pages = 243–50 | date = June 2008 | pmid = 18379759 | doi = 10.1007/s00213-008-1123-x | s2cid = 2126631 }}</ref> but these effects are minimal and transient. Overall, it seems that acute doses of opioids in non-tolerant subjects produce minor effects in some sensory and motor abilities, and perhaps also in [[attention]] and cognition. It is likely that the effects of morphine will be more pronounced in opioid-naive subjects than chronic opioid users.

In chronic opioid users, such as those on Chronic Opioid Analgesic Therapy (COAT) for managing severe, [[chronic pain]], behavioural testing has shown normal functioning on perception, cognition, coordination and behaviour in most cases. One 2000 study<ref>{{cite journal | vauthors = Galski T, Williams JB, Ehle HT | title = Effects of opioids on driving ability | journal = Journal of Pain and Symptom Management | volume = 19 | issue = 3 | pages = 200–8 | date = March 2000 | pmid = 10760625 | doi = 10.1016/S0885-3924(99)00158-X | doi-access = free }}</ref> analysed COAT patients to determine whether they were able to safely operate a motor vehicle. The findings from this study suggest that stable opioid use does not significantly impair abilities inherent in driving (this includes physical, cognitive and perceptual skills). COAT patients showed rapid completion of tasks that require the speed of responding for successful performance (e.g., [[Rey Complex Figure]] Test) but made more errors than controls. COAT patients showed no deficits in visual-spatial perception and organization (as shown in the [[Wechsler Adult Intelligence Scale|WAIS-R]] Block Design Test) but did show impaired immediate and short-term visual memory (as shown on the Rey Complex Figure Test&nbsp;– Recall). These patients showed no impairments in higher-order cognitive abilities (i.e., planning). COAT patients appeared to have difficulty following instructions and showed a propensity toward impulsive behaviour, yet this did not reach statistical significance. It is important to note that this study reveals that COAT patients have no domain-specific deficits, which supports the notion that chronic opioid use has minor effects on [[Psychomotor learning|psychomotor]], [[cognitive]], or [[neuropsychological]] functioning.

=== Reinforcement disorders ===

==== Addiction ====

[[File:Santiago Rusinol Before the Morphine.jpg|thumb|left|''Before the Morphine'' by [[Santiago Rusiñol]]]]

Morphine is a highly [[addictive]] substance. Numerous studies, including one by ''The Lancet'', ranked morphine/heroin as the #1 most addictive substance, followed by [[cocaine]] at #2, [[nicotine]] #3, [[barbiturates]] at #4, and [[ethanol]] at #5. In controlled studies comparing the physiological and subjective effects of [[heroin]] and morphine in individuals formerly addicted to opiates, subjects showed no preference for one drug over the other. Equipotent, injected doses had comparable action courses, with heroin crossing the [[blood–brain barrier]] slightly quicker. No difference in subjects' self-rated feelings of [[euphoria]], ambition, nervousness, relaxation, or drowsiness.<ref name="martin and fraser" /> Short-term addiction studies by the same researchers demonstrated that tolerance developed at a similar rate to both heroin and morphine. When compared to the opioids [[hydromorphone]], [[fentanyl]], [[oxycodone]], and [[pethidine]], former addicts showed a strong preference for heroin and morphine, suggesting that heroin and morphine are particularly susceptible to abuse and addiction. Morphine and heroin also produced higher rates of euphoria and other positive subjective effects when compared to these other opioids.<ref name="martin and fraser" /> The choice of heroin and morphine over other opioids by former drug addicts may also be because heroin is an ester of morphine and a morphine [[prodrug]], essentially meaning they are identical drugs ''in vivo''. Heroin is converted to morphine before binding to the [[opioid receptor]]s in the brain and spinal cord, where morphine causes the subjective effects, which is what the addicted individuals are seeking.<ref name="urlDrugFacts: Heroin | National Institute on Drug Abuse (NIDA)">{{cite web |url = http://www.nida.nih.gov/infofacts/heroin.html |title = Heroin |author = National Institute on Drug Abuse (NIDA) |date = April 2013 |website = DrugFacts |publisher = U.S. National Institutes of Health |url-status = dead |archive-url = https://web.archive.org/web/20051130022758/http://www.nida.nih.gov/Infofacts/heroin.html |archive-date = 30 November 2005 |access-date = 29 April 2008 }}</ref>

==== Tolerance ====
Several hypotheses are given about how tolerance develops, including opioid receptor [[phosphorylation]] (which would change the receptor conformation), functional decoupling of receptors from [[G-proteins]] (leading to receptor desensitization),<ref>{{cite journal | vauthors = Roshanpour M, Ghasemi M, Riazi K, Rafiei-Tabatabaei N, Ghahremani MH, Dehpour AR | title = Tolerance to the anticonvulsant effect of morphine in mice: blockage by ultra-low dose naltrexone | journal = Epilepsy Research | volume = 83 | issue = 2–3 | pages = 261–4 | date = February 2009 | pmid = 19059761 | doi = 10.1016/j.eplepsyres.2008.10.011 | s2cid = 21651602 }}</ref> μ-opioid receptor internalization or receptor down-regulation (reducing the number of available receptors for morphine to act on), and upregulation of the [[cyclic adenosine monophosphate|cAMP]] pathway (a counterregulatory mechanism to opioid effects) (For a review of these processes, see Koch and Hollt<ref>{{cite journal | vauthors = Koch T, Höllt V | title = Role of receptor internalization in opioid tolerance and dependence | journal = Pharmacology & Therapeutics | volume = 117 | issue = 2 | pages = 199–206 | date = February 2008 | pmid = 18076994 | doi = 10.1016/j.pharmthera.2007.10.003 }}</ref>).

==== Dependence and withdrawal ====
{{See also|Opioid use disorder|Opioid withdrawal}}
{{more citations needed|section|date=November 2019}}
Cessation of dosing with morphine creates the prototypical opioid withdrawal syndrome, which, unlike that of [[barbiturates]], [[benzodiazepines]], [[alcohol (drug)|alcohol]], or [[sedative]]-hypnotics, is not fatal by itself in otherwise healthy people.

Acute morphine withdrawal, along with that of any other opioid, proceeds through a number of stages. Other opioids differ in the intensity and length of each, and weak opioids and mixed agonist-antagonists may have acute withdrawal syndromes that do not reach the highest level. As commonly cited{{by whom|date=November 2010}}, they are:
* '''Stage I''', 6&nbsp;h to 14&nbsp;h after last dose: Drug craving, anxiety, irritability, perspiration, and mild to moderate [[dysphoria]]
* '''Stage II''', 14&nbsp;h to 18&nbsp;h after last dose: [[Yawn|Yawning]], heavy [[perspiration]], mild [[Depression (mood)|depression]], [[lacrimation]], [[crying]], headaches, runny nose, dysphoria, also intensification of the above symptoms, "yen sleep" (a waking trance-like state)
* '''Stage III''', 16&nbsp;h to 24&nbsp;h after last dose: Increase in all of the above, [[Mydriasis|dilated pupils]], [[Goose bumps|piloerection]] (goose bumps),<ref>{{cite web |url = http://www.merriam-webster.com/words-at-play/why-do-we-quit-cold-turkey |title = Why do We Quit 'Cold Turkey'? |access-date = 21 November 2016 |url-status = live |archive-url = https://web.archive.org/web/20161121175014/http://www.merriam-webster.com/words-at-play/why-do-we-quit-cold-turkey |archive-date = 21 November 2016 }}</ref> muscle twitches, [[Hot flash|hot flashes]], cold flashes, aching bones and muscles, [[Anorexia (symptom)|loss of appetite]], and the beginning of intestinal cramping
* '''Stage IV''', 24&nbsp;h to 36&nbsp;h after last dose: Increase in all of the above including severe cramping, [[restless leg syndrome|restless legs syndrome]] (RLS), loose stool, [[insomnia]], elevation of blood pressure, [[fever]], increase in frequency of breathing and tidal volume, [[tachycardia]] (elevated pulse), [[Psychomotor agitation|restlessness]], nausea
* '''Stage V''', 36&nbsp;h to 72&nbsp;h after last dose: Increase in all of the above, fetal position, vomiting, free and frequent liquid diarrhea, weight loss of 2&nbsp;kg to 5&nbsp;kg per 24&nbsp;h, increased [[White blood cell|white cell count]], and other blood changes
* '''Stage VI''', after completion of above: Recovery of appetite and normal bowel function, beginning of transition to [[Post-acute-withdrawal syndrome|post-acute withdrawal symptoms]] that are mainly psychological, but may also include increased sensitivity to pain, [[hypertension]], [[colitis]] or other gastrointestinal afflictions related to motility, and problems with weight control in either direction

In advanced stages of withdrawal, ultrasonographic evidence of pancreatitis has been demonstrated in some patients and is presumably attributed to spasm of the pancreatic [[sphincter of Oddi]].<ref>{{cite web |url = http://www.livestrong.com/article/68215-opiate-withdrawal-stages/ |title = Opiate Withdrawal Stages |access-date = 13 June 2014 |url-status = live |archive-url = https://web.archive.org/web/20140605063405/http://www.livestrong.com/article/68215-opiate-withdrawal-stages/ |archive-date = 5 June 2014 }}</ref>

The withdrawal symptoms associated with morphine addiction are usually experienced shortly before the time of the next scheduled dose, sometimes within as early as a few hours (usually 6&nbsp;h to 12&nbsp;h) after the last administration. Early symptoms include watery eyes, insomnia, diarrhea, runny nose, yawning, [[dysphoria]], sweating, and, in some cases, a strong drug craving. Severe headache, restlessness, [[irritability]], loss of appetite, body aches, severe abdominal pain, nausea and vomiting, tremors, and even stronger and more intense drug craving appear as the syndrome progresses. Severe depression and vomiting are very common. During the acute withdrawal period, systolic and diastolic blood pressures increase, usually beyond premorphine levels, and heart rate increases,<ref name="Chan, Irvine, and White">{{cite journal | vauthors = Chan R, Irvine R, White J | title = Cardiovascular changes during morphine administration and spontaneous withdrawal in the rat | journal = European Journal of Pharmacology | volume = 368 | issue = 1 | pages = 25–33 | date = February 1999 | pmid = 10096766 | doi = 10.1016/S0014-2999(98)00984-4 }}</ref> which have potential to cause a heart attack, blood clot, or stroke.

Chills or cold flashes with goose bumps alternating with flushing (hot flashes), kicking movements of the legs,<ref name="urlDrugFacts: Heroin | National Institute on Drug Abuse (NIDA)" />and excessive sweating are also characteristic symptoms.<ref name="urlDrugs and Human Performance FACT SHEETS – Morphine (and Heroin)">{{cite web |url = http://www.nhtsa.dot.gov/People/injury/research/job185drugs/morphine.htm |title = Morphine (and Heroin) |website = Drugs and Human Performance Fact Sheets |publisher = U.S. National Traffic Safety Administration |url-status = dead |archive-url = https://web.archive.org/web/20061003085645/http://www.nhtsa.dot.gov/people/injury/research/job185drugs/morphine.htm |archive-date = 3 October 2006 |access-date = 17 May 2007 }}</ref> Severe pains in the bones and muscles of the back and extremities occur, as do muscle spasms. At any point during this process, a suitable narcotic can be administered that will dramatically reverse the withdrawal symptoms. Major withdrawal symptoms peak between 48&nbsp;h and 96&nbsp;h after the last dose and subside after about 8 to 12 days. Sudden discontinuation of morphine by heavily [[Drug dependence|dependent]] users who are in poor health is very rarely fatal. Morphine withdrawal is considered less dangerous than alcohol, barbiturate, or benzodiazepine withdrawal.<ref>{{cite web |url = http://www.justice.gov/dea/concern/narcotics.html |title = Narcotics |website = DEA Briefs & Background, Drugs and Drug Abuse, Drug Descriptions |publisher = U.S. Drug Enforcement Administration |url-status = unfit |archive-url = https://web.archive.org/web/20120114150200/http://www.justice.gov/dea/concern/narcotics.html |archive-date = 14 January 2012 }}</ref><ref>{{cite book | vauthors = Dalrymple T |author-link = Theodore Dalrymple |title = Romancing Opiates: Pharmacological Lies and the Addiction Bureaucracy |publisher = Encounter |year = 2006 |pages = [https://archive.org/details/romancingopiates00theo/page/160 160] |url = https://archive.org/details/romancingopiates00theo/page/160 |isbn = 978-1-59403-087-1 }}</ref>

The psychological dependence associated with morphine [[Substance use disorder|addiction]] is complex and protracted. Long after the physical need for morphine has passed, addicts will usually continue to think and talk about the use of morphine (or other drugs) and feel strange or overwhelmed coping with daily activities without being under the influence of morphine. Psychological withdrawal from morphine is usually a very long and painful process. Addicts often experience severe depression, anxiety, insomnia, mood swings, forgetfulness, low [[self-esteem]], [[confusion]], [[paranoia]], and other psychological problems. Without intervention, the syndrome will run its course, and most of the overt physical symptoms will disappear within 7 to 10 days including psychological dependence. A high probability of relapse exists after morphine withdrawal when neither the physical environment nor the behavioral motivators that contributed to the abuse have been altered. Testimony to morphine's addictive and reinforcing nature is its relapse rate. Abusers of morphine have one of the highest relapse rates among all drug users, ranging up to 98% in the estimation of some medical experts.<ref>{{cite book | vauthors = O'Neil MJ |title = The Merck index : an encyclopedia of chemicals, drugs, and biological |year = 2006 |publisher = Merck |location = Whitehouse Station, N.J. |isbn = 978-0-911910-00-1 }}</ref>

== Toxicity ==
{{See also|Opioid overdose}}
{| border="1" cellspacing="0" cellpadding="3" style="margin: 0 0 0 0.5em; float: right; background: #FFFFFF; border-collapse: collapse; border-color: #C0C090;"
! {{Chemical datatable header}} | Properties of Morphine
|-
| [[Molar mass]]<ref name="CRC_85">{{cite book | veditors = Lide DR |title = CRC handbook of chemistry and physics: a ready-reference book of chemical and physical data |year = 2004 |edition = 85 |publisher = CRC Press |location = Boca Ratan Florida |isbn = 978-0-8493-0485-9 |url = https://archive.org/details/crchandbookofche81lide }}</ref>
| 285.338 g/mol
|-
| [[Acidity]] (p''K''<sub>a</sub>)<ref name="CRC_85" />
|
{|
| Step 1: 8.21 || at 25&nbsp;°C
|-
| Step 2: 9.85 || at 20&nbsp;°C
|}
|-
| [[Solubility]]<ref name="CRC_85" />
| 0.15 g/L at 20&nbsp;°C
|-
| [[Melting point]]<ref name="CRC_85" />
| 255&nbsp;°C
|-
| [[Boiling point]]<ref name="CRC_85" />
| 190&nbsp;°C sublimes
|-
|}

A large [[overdose]] can cause [[asphyxia]] and death by respiratory depression if the person does not receive medical attention immediately.<ref name=Duldner>{{cite web | url = https://www.nlm.nih.gov/medlineplus/ency/article/002502.htm | work = MedlinePlus | publisher = U.S. National Library of Medicine | title = Morphine overdose | archive-url = https://web.archive.org/web/20160524084700/https://www.nlm.nih.gov/medlineplus/ency/article/002502.htm | archive-date= 24 May 2016 | date = 2 March 2009 | vauthors = Duldner Jr JE }}</ref> Overdose treatment includes the administration of [[naloxone]]. The latter completely reverses morphine's effects, but may result in immediate onset of withdrawal in opiate-addicted subjects. Multiple doses may be needed as the duration of action of morphine is longer than that of naloxone.<ref>{{cite journal | vauthors = Boyer EW | title = Management of opioid analgesic overdose | journal = The New England Journal of Medicine | volume = 367 | issue = 2 | pages = 146–155 | date = July 2012 | pmid = 22784117 | pmc = 3739053 | doi = 10.1056/NEJMra1202561 }}</ref>

== Pharmacology ==
=== Pharmacodynamics ===
{| class="wikitable floatright" style="text-align: center;"
|+ Morphine at opioid receptors
|-
! rowspan="2" | Compound || colspan="3" | [[Binding affinity|Affinities]] ({{abbrlink|K<sub>i</sub>|Inhibitor constant}}) || Ratio || rowspan="2" | Ref
|-
! {{abbrlink|MOR|μ-Opioid receptor}} !! {{abbrlink|DOR|δ-Opioid receptor}} !! {{abbrlink|KOR|κ-Opioid receptor}} !! MOR:DOR:KOR
|-
| Morphine || 1.8 nM || 90 nM || 317 nM || 1:50:176 || <ref name="CorbettPaterson1993">{{cite book| vauthors = Corbett AD, Paterson SJ, Kosterlitz HW |chapter=Selectivity of Ligands for Opioid Receptors |title=Opioids |volume=104 / 1|year=1993|pages=645–679|issn=0171-2004|doi=10.1007/978-3-642-77460-7_26|series=Handbook of Experimental Pharmacology | publisher = Springer | location = Berlin, Heidelberg|isbn=978-3-642-77462-1}}</ref>
|-
| (−)-Morphine || 1.24 nM || 145 nM || 23.4 nM || 1:117:19 || <ref name="pmid7562497">{{cite journal | vauthors = Codd EE, Shank RP, Schupsky JJ, Raffa RB | title = Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 274 | issue = 3 | pages = 1263–70 | date = September 1995 | pmid = 7562497 }}</ref>
|-
| (+)-Morphine || >10 μM || >100 μM || >300 μM || {{abbr|ND|No data}} || <ref name="pmid7562497" />
|}

{| class="wikitable floatright"
|+ <br />Equianalgesic doses<ref name="King2010">{{cite book| vauthors = King TL, Brucker MC |title=Pharmacology for Women's Health|url=https://books.google.com/books?id=o_rHHCsIpckC&pg=PA332|date=25 October 2010|publisher=Jones & Bartlett Publishers|isbn=978-1-4496-1073-9|pages=332–}}</ref><ref name="ChestnutWong2014">{{cite book | vauthors = Flood P, Aleshi P | chapter = Postoperative and chronic pain: systemic and regional pain techniques | veditors = Chestnut DH, Wong CA, Tsen KC, Ngan Kee WD, Beilin Y, Mhyre J |title=Chestnut's Obstetric Anesthesia: Principles and Practice E-Book|chapter-url=https://books.google.com/books?id=FMU0AwAAQBAJ&pg=PA611|date=28 February 2014|publisher=Elsevier Health Sciences|isbn=978-0-323-11374-8|pages=611–}}</ref><ref name="Tiziani2013">{{cite book| vauthors = Tiziani AP |title=Havard's Nursing Guide to Drugs|url=https://books.google.com/books?id=XpzQAgAAQBAJ&pg=PA933|date=1 June 2013|publisher=Elsevier Health Sciences|isbn=978-0-7295-8162-2|pages=933–}}</ref>
|-
! Compound !! [[Route of administration|Route]] !! [[Dose (biochemistry)|Dose]]
|-
| [[Codeine]] || {{abbr|PO|Oral administration}} || 200&nbsp;mg
|-
| [[Hydrocodone]] || {{abbr|PO|Oral administration}} || 30&nbsp;mg
|-
| [[Hydromorphone]] || {{abbr|PO|Oral administration}} || 7.5&nbsp;mg
|-
| [[Hydromorphone]] || {{abbr|IV|Intravenous administration}} || 2&nbsp;mg
|-
| Morphine || {{abbr|PO|Oral administration}} || 30&nbsp;mg
|-
| Morphine || {{abbr|IV|Intravenous administration}} || 10&nbsp;mg
|-
| [[Oxycodone]] || {{abbr|PO|Oral administration}} || 20&nbsp;mg
|-
| [[Oxycodone]] || {{abbr|IV|Intravenous administration}} || 20&nbsp;mg
|-
| [[Oxymorphone]] || {{abbr|PO|Oral administration}} || 10&nbsp;mg
|-
| [[Oxymorphone]] || {{abbr|IV|Intravenous administration}} || 1&nbsp;mg
|}

Due to its long history and established use as a pain medication, this compound has become the benchmark to which all other opioids are compared.<ref>{{cite book | vauthors = Ogura T, Egan TD |title = Pharmacology and physiology for anesthesia : foundations and clinical application |date = 2013 |publisher = Elsevier/Saunders |location = Philadelphia, PA |isbn = 978-1-4377-1679-5 |doi=10.1016/B978-1-4377-1679-5.00015-6 |chapter = Chapter 15 – Opioid Agonists and Antagonists }}</ref> It interacts predominantly with the μ–δ-opioid (Mu-Delta) [[GPCR oligomer|receptor heteromer]].<ref>{{cite journal | vauthors = Yekkirala AS, Kalyuzhny AE, Portoghese PS | title = Standard opioid agonists activate heteromeric opioid receptors: evidence for morphine and [d-Ala(2)-MePhe(4)-Glyol(5)]enkephalin as selective μ-δ agonists | journal = ACS Chemical Neuroscience | volume = 1 | issue = 2 | pages = 146–54 | date = February 2010 | pmid = 22816017 | pmc = 3398540 | doi = 10.1021/cn9000236 }}</ref><ref>{{cite journal | vauthors = Yekkirala AS, Banks ML, Lunzer MM, Negus SS, Rice KC, Portoghese PS | title = Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys | journal = ACS Chemical Neuroscience | volume = 3 | issue = 9 | pages = 720–7 | date = September 2012 | pmid = 23019498 | pmc = 3447399 | doi = 10.1021/cn300049m }}</ref> The μ-binding sites are discretely distributed in the [[human brain]], with high densities in the posterior [[amygdala]], [[hypothalamus]], [[thalamus]], [[nucleus caudatus]], [[putamen]], and certain cortical areas. They are also found on the [[chemical synapse|terminal axons]] of primary afferents within laminae [[posteromarginal nucleus|I]] and II ([[substantia gelatinosa of Rolando|substantia gelatinosa]]) of the spinal cord and in the spinal nucleus of the [[trigeminal nerve]].<ref name="rxlist.com">{{cite web |url = http://www.rxlist.com/cgi/generic/ms_cp.htm |title = MS-Contin (Morphine Sulfate Controlled-Release) Drug Information: Clinical Pharmacology |website = Prescribing Information |publisher = RxList |url-status = dead |archive-url = https://web.archive.org/web/20070515141904/http://www.rxlist.com/cgi/generic/ms_cp.htm |archive-date = 15 May 2007 }}</ref>

Morphine is a [[phenanthrene]] [[opioid receptor]] [[receptor agonist|agonist]]&nbsp;– its main effect is binding to and activating the [[μ-opioid receptor]] (MOR) in the [[central nervous system]]. Its [[intrinsic activity]] at the MOR is heavily dependent on the [[assay]] and tissue being tested; in some situations it is a [[full agonist]] while in others it can be a [[partial agonist]] or even [[receptor antagonist|antagonist]].<ref name="pmid23646826">{{cite journal | vauthors = Kelly E | title = Efficacy and ligand bias at the μ-opioid receptor | journal = British Journal of Pharmacology | volume = 169 | issue = 7 | pages = 1430–46 | date = August 2013 | pmid = 23646826 | pmc = 3724102 | doi = 10.1111/bph.12222 }}</ref> In clinical settings, morphine exerts its principal pharmacological effect on the central nervous system and [[human gastrointestinal tract|gastrointestinal tract]]. Its primary actions of therapeutic value are analgesia and sedation. Activation of the MOR is associated with analgesia, sedation, [[euphoria (emotion)|euphoria]], physical [[chemical dependency|dependence]], and [[respiratory depression]]. Morphine is also a [[κ-opioid receptor]] (KOR) and [[δ-opioid receptor]] (DOR) agonist. Activation of the KOR is associated with spinal analgesia, [[miosis]] (pinpoint pupils), and [[psychotomimetic]] effects. The DOR is thought to play a role in analgesia.<ref name="rxlist.com" />{{Failed verification|date=August 2023}} Although morphine does not bind to the [[sigma receptor|σ receptor]], it has been shown that σ receptor agonists, such as [[pentazocine|(+)-pentazocine]], inhibit morphine analgesia, and σ receptor antagonists enhance morphine analgesia,<ref>{{cite journal | vauthors = Chien CC, Pasternak GW | title = Sigma antagonists potentiate opioid analgesia in rats | journal = Neuroscience Letters | volume = 190 | issue = 2 | pages = 137–9 | date = May 1995 | pmid = 7644123 | doi = 10.1016/0304-3940(95)11504-P | s2cid = 10033780 | doi-access = free }}</ref> suggesting downstream involvement of the σ receptor in the actions of morphine.

The effects of morphine can be countered with [[opioid receptor antagonist]]s such as [[naloxone]] and [[naltrexone]]; the development of tolerance to morphine may be inhibited by [[NMDA receptor antagonist]]s such as [[ketamine]], [[dextromethorphan]], and [[memantine]].<ref name="pmid8747752">{{cite journal | vauthors = Herman BH, Vocci F, Bridge P | title = The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal. Medication development issues for opiate addiction | journal = Neuropsychopharmacology | volume = 13 | issue = 4 | pages = 269–293 | date = December 1995 | pmid = 8747752 | doi = 10.1016/0893-133X(95)00140-9 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Popik P, Kozela E, Danysz W | title = Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 361 | issue = 4 | pages = 425–432 | date = April 2000 | pmid = 10763858 | doi = 10.1007/s002109900205 | s2cid = 18200635 }}</ref> The rotation of morphine with chemically dissimilar opioids in the long-term treatment of pain will slow down the growth of tolerance in the longer run, particularly agents known to have significantly incomplete cross-tolerance with morphine such as [[levorphanol]], [[ketobemidone]], [[piritramide]], and [[methadone]] and its derivatives; all of these drugs also have NMDA antagonist properties. It is believed that the strong opioid with the most incomplete cross-tolerance with morphine is either methadone<ref>{{cite journal | vauthors = Crews JC, Sweeney NJ, Denson DD | title = Clinical efficacy of methadone in patients refractory to other mu-opioid receptor agonist analgesics for management of terminal cancer pain. Case presentations and discussion of incomplete cross-tolerance among opioid agonist analgesics | journal = Cancer | volume = 72 | issue = 7 | pages = 2266–2272 | date = October 1993 | pmid = 7690683 | doi = 10.1002/1097-0142(19931001)72:7<2266::AID-CNCR2820720734>3.0.CO;2-P | s2cid = 19669811 }}</ref> or [[dextromoramide]].{{Citation needed|date=October 2021}}
[[File:Morphine_Ampoule_For_Veterinary_Use.jpg|thumb|Morphine [[hydrochloride]] ampoule for [[Veterinary medicine|veterinary use]]]]

==== Analgesia creation ====
Morphine creates analgesia through the activation of a specific group of neurons in the [[rostral ventromedial medulla]], called the "morphine ensemble."<ref name="j866">{{cite journal | vauthors = Fatt MP, Zhang MD, Kupari J, Altınkök M, Yang Y, Hu Y, Svenningsson P, Ernfors P |date=30 August 2024 |title=Morphine-responsive neurons that regulate mechanical antinociception |journal=Science |volume=385 |issue=6712 |pages=eado6593 |doi=10.1126/science.ado6593 |pmid=39208104 |issn=0036-8075|pmc=7616448 |bibcode=2024Sci...385o6593F }}</ref> This ensemble includes glutamatergic neurons that project to spinal cord, known as RVM<sup>BDNF</sup> neurons. These neurons connect to inhibitory neurons in the spinal cord, called SC<sup>Gal</sup> neurons, which release the neurotransmitter GABA and the neuropeptide [[galanin]]. The inhibition of SC<sup>Gal</sup> neurons is crucial for morphine's pain-relieving effects. Additionally, the neurotrophic factor [[Brain-derived neurotrophic factor|BDNF]], produced within the RVM<sup>BDNF</sup> neurons, is required for morphine's action. Increasing BDNF levels enhances morphine's analgesic effects, even at lower doses.<ref name="v878">{{cite journal | vauthors = De Preter CC, Heinricher MM |date=30 August 2024 |title=Opioid circuit opens path to pain relief |journal=Science |volume=385 |issue=6712 |pages=932–933 |doi=10.1126/science.adr5900 |pmid=39208119 |bibcode=2024Sci...385..932D |issn=0036-8075}}</ref><ref name="j866" />

==== Gene expression ====
Studies have shown that morphine can alter the expression of a number of [[genes]]. A single injection of morphine has been shown to alter the expression of two major groups of genes, for proteins involved in [[mitochondria]]l respiration and for [[cytoskeleton]]-related proteins.<ref>{{cite journal | vauthors = Loguinov AV, Anderson LM, Crosby GJ, Yukhananov RY | title = Gene expression following acute morphine administration | journal = Physiological Genomics | volume = 6 | issue = 3 | pages = 169–81 | date = August 2001 | pmid = 11526201 | doi = 10.1152/physiolgenomics.2001.6.3.169 | s2cid = 9296949 }}</ref>

==== Effects on the immune system ====
Morphine has long been known to act on receptors expressed on cells of the [[central nervous system]] resulting in pain relief and [[analgesia]]. In the 1970s and '80s, evidence suggesting that opioid drug addicts show increased risk of infection (such as increased [[pneumonia]], [[tuberculosis]], and [[HIV/AIDS]]) led scientists to believe that morphine may also affect the [[immune system]]. This possibility increased interest in the effect of chronic morphine use on the immune system.<ref>{{cite journal | vauthors = Sacerdote P | title = Opioids and the immune system | journal = Palliative Medicine | volume = 20 | pages = s9-15 | date = 2006 | issue = Suppl 1 | doi = 10.1191/0269216306pm1124oa | pmid = 16764216 | s2cid = 39489581 }}</ref>

The first step of determining that morphine may affect the immune system was to establish that the opiate receptors known to be expressed on cells of the central nervous system are also expressed on cells of the immune system. One study successfully showed that [[dendritic cells]], part of the innate immune system, display opiate receptors. Dendritic cells are responsible for producing [[cytokine]]s, which are the tools for communication in the immune system. This same study showed that dendritic cells chronically treated with morphine during their differentiation produce more [[interleukin-12]] (IL-12), a cytokine responsible for promoting the proliferation, growth, and differentiation of T-cells (another cell of the adaptive immune system) and less [[interleukin-10]] (IL-10), a cytokine responsible for promoting a B-cell immune response (B cells produce antibodies to fight off infection).<ref name="messmer 2006">{{cite journal | vauthors = Messmer D, Hatsukari I, Hitosugi N, Schmidt-Wolf IG, Singhal PC | title = Morphine reciprocally regulates IL-10 and IL-12 production by monocyte-derived human dendritic cells and enhances T cell activation | journal = Molecular Medicine | volume = 12 | issue = 11–12 | pages = 284–90 | year = 2006 | pmid = 17380193 | pmc = 1829197 | doi = 10.2119/2006-00043.Messmer }}</ref>

This regulation of cytokines appear to occur via the [[p38 MAPK pathway|p38 MAPKs (mitogen-activated protein kinase)-dependent pathway]]. Usually, the p38 within the dendritic cell expresses [[TLR 4]] (toll-like receptor 4), which is activated through the ligand LPS ([[lipopolysaccharide]]). This causes the p38 MAPK to be [[phosphorylation|phosphorylated]]. This phosphorylation activates the [[p38 mitogen-activated protein kinases|p38 MAPK]] to begin producing IL-10 and IL-12. When the dendritic cells are chronically exposed to morphine during their differentiation process then treated with LPS, the production of cytokines is different. Once treated with morphine, the p38 MAPK does not produce IL-10, instead favoring production of IL-12. The exact mechanism through which the production of one cytokine is increased in favor over another is not known. Most likely, the morphine causes increased phosphorylation of the p38 MAPK. Transcriptional level interactions between IL-10 and IL-12 may further increase the production of IL-12 once IL-10 is not being produced. This increased production of IL-12 causes increased T-cell immune response.

Further studies on the effects of morphine on the immune system have shown that morphine influences the production of [[neutrophils]] and other [[cytokines]]. Since cytokines are produced as part of the immediate immunological response ([[inflammation]]), it has been suggested that they may also influence pain. In this way, cytokines may be a logical target for analgesic development. Recently, one study has used an animal model (hind-paw incision) to observe the effects of morphine administration on the acute immunological response. Following hind-paw incision, pain thresholds and cytokine production were measured. Normally, cytokine production in and around the wounded area increases in order to fight [[infection]] and control healing (and, possibly, to control pain), but pre-incisional morphine administration (0.1&nbsp;mg/kg to 10.0&nbsp;mg/kg) reduced the number of cytokines found around the wound in a dose-dependent manner. The authors suggest that morphine administration in the acute post-injury period may reduce resistance to infection and may impair the healing of the wound.<ref name="pmid17908329">{{cite journal | vauthors = Clark JD, Shi X, Li X, Qiao Y, Liang D, Angst MS, Yeomans DC | title = Morphine reduces local cytokine expression and neutrophil infiltration after incision | journal = Molecular Pain | volume = 3 | pages = 1744-8069-3-28 | date = October 2007 | pmid = 17908329 | pmc = 2096620 | doi = 10.1186/1744-8069-3-28 | doi-access = free }}</ref>

=== Pharmacokinetics ===
==== Absorption and metabolism ====
Morphine can be taken [[oral administration|orally]], [[Sublingual administration|sublingually]], [[Buccal space|bucally]], [[rectal administration|rectally]], [[subcutaneous injection|subcutaneously]], [[Insufflation (medicine)|intranasally]], [[intravenous]]ly, [[intrathecal]]ly or [[epidural]]ly and inhaled via a nebulizer. As a recreational drug, it is becoming more common to inhale ("[[Chasing the Dragon]]"), but, for medical purposes, intravenous (IV) injection is the most common method of administration. Morphine is subject to extensive [[first-pass metabolism]] (a large proportion is broken down in the liver), so, if taken orally, only 40% to 50% of the dose reaches the central nervous system. Resultant plasma levels after subcutaneous (SC), intramuscular (IM), and IV injection are all comparable. After IM or SC injections, morphine plasma levels peak in approximately 20&nbsp;min, and, after oral administration, levels peak in approximately 30&nbsp;min.<ref>{{cite journal | vauthors = Trescot AM, Datta S, Lee M, Hansen H | title = Opioid pharmacology | journal = Pain Physician | volume = 11 | issue = 2 Suppl | pages = S133-53 | date = March 2008 | doi = 10.36076/ppj.2008/11/S133 | pmid = 18443637 }}</ref> Morphine is [[metabolised]] primarily in the [[liver]] and approximately 87% of a dose of morphine is excreted in the [[urine]] within 72&nbsp;h of administration. Morphine is metabolized primarily into [[morphine-3-glucuronide]] (M3G) and [[morphine-6-glucuronide]] (M6G)<ref name="Kilpatrick_2005">{{cite journal | vauthors = Kilpatrick GJ, Smith TW | title = Morphine-6-glucuronide: actions and mechanisms | journal = Medicinal Research Reviews | volume = 25 | issue = 5 | pages = 521–44 | date = September 2005 | pmid = 15952175 | doi = 10.1002/med.20035 | s2cid = 20887610 }}</ref> via [[glucuronidation]] by phase II metabolism enzyme [[UGT2B7|UDP-glucuronosyl transferase-2B7]] (UGT2B7). About 60% of morphine is converted to M3G, and 6% to 10% is converted to M6G.<ref name="van Dorp" /> Not only does the metabolism occur in the liver but it may also take place in the brain and the kidneys. M3G does not undergo opioid receptor binding and has no analgesic effect. M6G binds to μ-receptors and is half as potent an analgesic as morphine in humans.<ref name="van Dorp">{{cite journal | vauthors = van Dorp EL, Romberg R, Sarton E, Bovill JG, Dahan A | title = Morphine-6-glucuronide: morphine's successor for postoperative pain relief? | journal = Anesthesia and Analgesia | volume = 102 | issue = 6 | pages = 1789–97 | date = June 2006 | pmid = 16717327 | doi = 10.1213/01.ane.0000217197.96784.c3 | s2cid = 18890026 | url = http://www.anesthesia-analgesia.org/cgi/content/full/102/6/1789 | url-status = live | archive-url = https://web.archive.org/web/20081201234703/http://www.anesthesia-analgesia.org/cgi/content/full/102/6/1789 | archive-date = 1 December 2008 | doi-access = free }}</ref> Morphine may also be metabolized into small amounts of [[normorphine]], [[codeine]], and [[hydromorphone]]. Metabolism rate is determined by gender, age, diet, genetic makeup, disease state (if any), and use of other medications. The elimination [[half-life]] of morphine is approximately 120&nbsp;min, though there may be slight differences between men and women. Morphine can be stored in fat, and, thus, can be detectable even after death. Morphine can cross the [[blood–brain barrier]], but, because of poor lipid solubility, protein binding, rapid conjugation with glucuronic acid and ionization, it does not cross easily. [[Heroin]], which is derived from morphine, crosses the blood–brain barrier more easily, making it more potent.<ref name="Jenkins AJ 2008">Jenkins AJ (2008) Pharmacokinetics of specific drugs. In Karch SB (''Ed''), ''Pharmacokinetics and pharmacodynamics of abused drugs''. CRC Press: Boca Raton.</ref>

==== Extended-release ====
{{Main|Extended-release morphine}}
There are [[Time release technology|extended-release]] formulations of orally administered morphine whose effect last longer, which can be given once per day. Brand names for this formulation of morphine include Avinza,<ref name=maryland /> Kadian,<ref name=maryland /> MS Contin<ref name=maryland>{{cite web |url = https://umm.edu/health/medical/drug-notes/notes/morphine-slow-release-by-mouth |title = Morphine, slow release (By mouth) |website = [[University of Maryland Medical Center]] |url-status = live |archive-url = https://web.archive.org/web/20151222173053/https://umm.edu/health/medical/drug-notes/notes/morphine-slow-release-by-mouth |archive-date = 22 December 2015 }}</ref> and Dolcontin.<ref name="PedersenFredheim2015">{{cite journal | vauthors = Pedersen L, Fredheim O | title = Opioids for chronic noncancer pain: still no evidence for superiority of sustained-release opioids | journal = Clinical Pharmacology and Therapeutics | volume = 97 | issue = 2 | pages = 114–5 | date = February 2015 | pmid = 25670511 | doi = 10.1002/cpt.26 | s2cid = 5603973 }} Last reviewed on 18 November 2015</ref> For constant pain, the relieving effect of extended-release morphine given once (for Kadian)<ref name=medscape>{{cite web |url = http://reference.medscape.com/drug/ms-contin-astramorph-morphine-343319 |title = Dosing & Uses |website = [[Medscape]] |access-date = 21 December 2015 |url-status = live |archive-url = https://web.archive.org/web/20151031152616/http://reference.medscape.com/drug/ms-contin-astramorph-morphine-343319 |archive-date = 31 October 2015 }}</ref> or twice (for MS Contin)<ref name=medscape /> every 24 hours is roughly the same as multiple administrations of ''immediate release'' (or "regular") morphine.<ref name=northwestern>{{cite web |url = http://endoflife.northwestern.edu/pain_management/morphine.pdf |title = EndLink: An Internet-based End of Life Care Education Program – Morphine Dosing |website = [[Northwestern University]] |url-status = live |archive-url = https://web.archive.org/web/20160304092914/http://endoflife.northwestern.edu/pain_management/morphine.pdf |archive-date = 4 March 2016 }}</ref> Extended-release morphine can be administered together with "rescue doses" of immediate-release morphine as needed in case of breakthrough pain, each generally consisting of 5% to 15% of the 24-hour extended-release dosage.<ref name=northwestern />

==== Detection in body fluids ====
Morphine and its major metabolites, morphine-3-glucuronide and morphine-6-glucuronide, can be detected in blood, plasma, hair, and urine using an [[immunoassay]]. [[Chromatography]] can be used to test for each of these substances individually. Some testing procedures [[hydrolysis|hydrolyze]] metabolic products into morphine before the immunoassay, which must be considered when comparing morphine levels in separately published results. Morphine can also be isolated from whole blood samples by [[solid phase extraction]] (SPE) and detected using [[liquid chromatography-mass spectrometry]] (LC-MS).

Ingestion of codeine or food containing poppy seeds can cause false positives.<ref>{{cite book | vauthors = Baselt RC |title = Disposition of Toxic Drugs and Chemicals in Man |year = 2008 |edition = 8th |publisher = Biomedical Publications |location = Foster City, CA |isbn = 978-0-9626523-7-0 |pages = 1057–1062 }}</ref>

A 1999 review estimated that relatively low doses of heroin (which metabolizes immediately into morphine) are detectable by standard urine tests for 1–1.5 days after use.<ref name="pmid11484423">{{cite journal | vauthors = Vandevenne M, Vandenbussche H, Verstraete A | title = Detection time of drugs of abuse in urine | journal = Acta Clinica Belgica | volume = 55 | issue = 6 | pages = 323–33 | year = 2000 | pmid = 11484423 | doi = 10.1080/17843286.2000.11754319 | s2cid = 43808583 }}</ref> A 2009 review determined that, when the [[analyte]] is morphine and the [[limit of detection]] is 1{{space}}ng/ml, a 20{{space}}mg intravenous (IV) dose of morphine is detectable for 12–24 hours. A limit of detection of 0.6{{space}}ng/ml had similar results.<ref name="pmid15228165">{{cite journal | vauthors = Verstraete AG | title = Detection times of drugs of abuse in blood, urine, and oral fluid | journal = Therapeutic Drug Monitoring | volume = 26 | issue = 2 | pages = 200–5 | date = April 2004 | pmid = 15228165 | doi = 10.1097/00007691-200404000-00020 | s2cid = 385874 }}</ref>

=== Chirality and biological activity ===
Morphine is a pentacyclic 3°amine (alkaloid) with '''5 stereogenic centers''' and exists in '''32 stereoisomeric forms'''. But the desired analgesic activity resides exclusively in the natural product, the (-)-enantiomer with the configuration ('''5R,6S,9R,13S,14R).'''<ref>{{cite book | vauthors = Eliel EL, Wilen SH, Mander LN |url=https://www.worldcat.org/oclc/27642721 |title=Stereochemistry of organic compounds |date=1994 |publisher=Wiley |isbn=0-471-01670-5 |location=New York |oclc=27642721}}</ref><ref>{{cite web |title=Morphine – Chiralpedia |date=18 July 2022 |url=https://chiralpedia.com/blog/morphine/ |access-date=28 August 2022 }}</ref>

== Natural occurrence ==
{{See also|Opium}}
[[File:Slaapbol R0017600.JPG|thumb|Latex bleeding from a freshly-scored seed pod]]
Morphine is the most abundant opiate found in [[opium]], the dried [[latex]] extracted by shallowly scoring the unripe seedpods of the ''[[Papaver somniferum]]'' poppy. Morphine is generally 8–14% of the dry weight of opium.<ref name=Kapoor>{{cite book | vauthors = Kapoor L |title = Opium Poppy: Botany, Chemistry, and Pharmacology |year = 1995 |publisher = CRC Press |location = United States |isbn = 978-1-56024-923-8 |pages = 164 }}</ref> Przemko and Norman cultivars of the opium poppy, are used to produce two other alkaloids, [[thebaine]] and [[oripavine]], which are used in the manufacture of semi-synthetic and synthetic opioids like [[oxycodone]] and [[etorphine]]. ''[[Papaver bracteatum|P. bracteatum]]'' does not contain morphine or [[codeine]], or other narcotic [[phenanthrene]]-type, alkaloids. This species is rather a source of [[thebaine]].<ref name="pmid925935">{{cite journal | vauthors = Vincent PG, Bare CE, Gentner WA | title = Thebaine content of selections of Papaver bracteatum Lindl. at different ages | journal = Journal of Pharmaceutical Sciences | volume = 66 | issue = 12 | pages = 1716–9 | date = December 1977 | pmid = 925935 | doi = 10.1002/jps.2600661215 }}</ref> Occurrence of morphine in other [[Papaverales]] and [[Papaveraceae]], as well as in some species of [[hops]] and [[mulberry]] trees has not been confirmed. Morphine is produced most predominantly early in the life cycle of the plant. Past the optimum point for extraction, various processes in the plant produce codeine, [[thebaine]], and in some cases negligible amounts of [[hydromorphone]], [[dihydromorphine]], [[dihydrocodeine]], tetrahydro-thebaine, and [[hydrocodone]] (these compounds are rather synthesized from thebaine and oripavine).

In the brain of mammals, morphine is detectable in trace steady-state concentrations.<ref name="St2012" /> The human body also produces [[endorphins]], which are chemically related [[endogenous opioid]] [[peptide]]s that function as [[neuropeptide]]s and have similar effects to morphine.<ref>{{cite book | vauthors = Stewart O |title = Functional Neuroscience |year = 2000 |publisher = Springer |location = New York |isbn = 978-0-387-98543-5 |page = 116 |url = https://books.google.com/books?id=nNH3p29wjK4C&q=endorphins+neurotransmitter&pg=PA116 }}</ref>

===Human biosynthesis===
{{expand section|with = a more standard presentation, without a scheme-in-text, and with description of key enzymes, points of pathway regulation, etc | small = no | date=October 2016}}
Morphine is an [[endogenous opioid]] in humans. Various human cells are capable of synthesizing and releasing it, including [[white blood cell]]s.<ref name="St2012" /><ref name="IUPHAR - μ-opioid receptor">{{cite web |title = μ receptor |url = http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=319 |website = IUPHAR/BPS Guide to PHARMACOLOGY |publisher = International Union of Basic and Clinical Pharmacology |access-date = 28 December 2017 |date = 15 March 2017 |quote = Morphine occurs endogenously |url-status = live |archive-url = https://web.archive.org/web/20171107055107/http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=319 |archive-date = 7 November 2017 }}</ref><ref name="Poeaknapo_2004">{{cite journal | vauthors = Poeaknapo C, Schmidt J, Brandsch M, Dräger B, Zenk MH | title = Endogenous formation of morphine in human cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 39 | pages = 14091–6 | date = September 2004 | pmid = 15383669 | pmc = 521124 | doi = 10.1073/pnas.0405430101 | quote = Without doubt, human cells can produce the alkaloid morphine. | bibcode = 2004PNAS..10114091P | doi-access = free }}</ref> The primary biosynthetic pathway for morphine in humans consists of:<ref name="St2012" />
[[File:Morphine biosynthesis in humans.png|alt=Morphine biosynthesis in humans|center|thumb|770x770px|Morphine biosynthesis in humans]]
:[[L-tyrosine]] → [[tyramine|''para''-tyramine]] or [[L-DOPA]] → [[Dopamine]]
:L-tyrosine → L-DOPA → [[3,4-dihydroxyphenylacetaldehyde]] (DOPAL)
:Dopamine + DOPAL → [[tetrahydropapaveroline|(''S'')-norlaudanosoline]] →→→ (''S'')-[[reticuline]] → [[1,2-dehydroreticulinium]] → (''R'')-reticuline → [[salutaridine]] → [[salutaridinol]] → [[thebaine]] → [[neopinone]] → [[codeinone]] → [[codeine]] → morphine
The intermediate (''S'')-norlaudanosoline (also known as tetrahydropapaveroline) is synthesized through addition of DOPAL and dopamine.<ref name="St2012" /> [[CYP2D6]], a [[cytochrome P450]] isoenzyme is involved in two steps along the biosynthetic pathway, catalyzing both the biosynthesis of dopamine from tyramine and of morphine from codeine.<ref name="St2012" /><ref name="CYP2D6 tyramine-dopamine metabolism">{{cite journal | vauthors = Wang X, Li J, Dong G, Yue J | title = The endogenous substrates of brain CYP2D | journal = European Journal of Pharmacology | volume = 724 | pages = 211–8 | date = February 2014 | pmid = 24374199 | doi = 10.1016/j.ejphar.2013.12.025 | quote = Additionally, CYP2D is involved in the synthesis of endogenous morphine from various precursors, including L-3,4-dihydroxyphenylalanine (L-DOPA), reticulin, tetrahydropapaveroline (THP), and tyramine (Kulkarni, 2001; Mantione et al., 2008; Zhu, 2008). }}</ref>

Urinary concentrations of endogenous codeine and morphine have been found to significantly increase in individuals taking [[L-DOPA]] for the treatment of [[Parkinson's disease]].<ref name="St2012" />

===Biosynthesis in the opium poppy===
[[File:Morphine biosynthesis.png|thumb|center|750px|Morphine biosynthesis in the opium poppy]]
Biosynthesis of morphine in the [[Papaver somniferum|opium poppy]] begins with two tyrosine derivatives, [[dopamine]] and [[4-hydroxyphenylacetaldehyde]]. Condensation of these precursors yields the primary intermediate [[higenamine]] (norcoclaurine).<ref>{{cite journal | vauthors = Onoyovwe A, Hagel JM, Chen X, Khan MF, Schriemer DC, Facchini PJ | title = Morphine biosynthesis in opium poppy involves two cell types: sieve elements and laticifers | journal = Plant Cell | volume = 25 | issue = 10 | pages = 4110–4122 | date = 2013 | pmid = 24104569 | pmc = 3877807 | doi = 10.1105/tpc.113.115113 | doi-access = free | bibcode = 2013PlanC..25.4110O }}</ref> Subsequent action of four enzymes yields the tetrahydroisoquinoline [[reticuline]], which is converted into [[salutaridine]], [[thebaine]], and [[oripavine]]. The enzymes involved in this process are the [[salutaridine synthase]], [[Salutaridine reductase (NADPH)|salutaridine:NADPH 7-oxidoreductase]] and the [[Codeinone reductase (NADPH)|codeinone reductase]].<ref>{{cite journal |vauthors = Novak B, Hudlicky T, Reed J, Mulzer J, Trauner D |title = Morphine Synthesis and Biosynthesis-An Update |journal = Current Organic Chemistry |date = March 2000 |volume = 4 |issue = 3 |pages = 343–362 |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 = 19 June 2012 |citeseerx = 10.1.1.515.9096 }}</ref> Researchers are attempting to reproduce the biosynthetic pathway that produces morphine in [[genetically engineered]] [[yeast]].<ref>{{cite magazine |url = https://www.newscientist.com/article/dn27546-home-brew-heroin-soon-anyone-will-be-able-to-make-illegal-drugs/ |title = Home-brew heroin: soon anyone will be able to make illegal drugs |magazine = New Scientist | vauthors = Le Page M |date = 18 May 2015 |url-status = live |archive-url = https://web.archive.org/web/20160413033207/https://www.newscientist.com/article/dn27546-home-brew-heroin-soon-anyone-will-be-able-to-make-illegal-drugs/ |archive-date = 13 April 2016 }}</ref> In June 2015 the ''S''-reticuline could be produced from sugar and ''R''-reticuline could be converted to morphine, but the intermediate reaction could not be performed.<ref>{{cite web |url = https://www.science.org/content/article/final-step-sugar-morphine-conversion-deciphered |title = Final step in sugar-to-morphine conversion deciphered |publisher = Science | vauthors = Service RF |date = 25 June 2015 |url-status = live |archive-url = https://web.archive.org/web/20150821122148/http://news.sciencemag.org/biology/2015/06/final-step-sugar-morphine-conversion-deciphered |archive-date = 21 August 2015 }}</ref> In August 2015 the first complete synthesis of thebaine and hydrocodone in yeast was reported, but the process would need to be 100,000 times more productive to be suitable for commercial use.<ref>{{cite journal | vauthors = Galanie S, Thodey K, Trenchard IJ, Filsinger Interrante M, Smolke CD | title = Complete biosynthesis of opioids in yeast | journal = Science | volume = 349 | issue = 6252 | pages = 1095–100 | date = September 2015 | pmid = 26272907 | pmc = 4924617 | doi = 10.1126/science.aac9373 | bibcode = 2015Sci...349.1095G }}</ref><ref>{{cite web |title = Yeast-Based Opioid Production Completed |url = http://mobile.the-scientist.com/article/43739/yeast-based-opioid-production-completed |access-date = 15 August 2015 |date = 13 August 2015 |url-status = live |archive-url = https://web.archive.org/web/20150907025856/http://mobile.the-scientist.com/article/43739/yeast-based-opioid-production-completed |archive-date = 7 September 2015 }}</ref>

== Chemistry ==
{{multiple issues | section = yes |
 {{unreferenced section| date = February 2020}}
 {{original research|section| date = February 2020}}
}}
Elements of the morphine structure have been used to create completely synthetic drugs such as the [[morphinan]] family ([[levorphanol]], [[dextromethorphan]] and others) and other groups that have many members with morphine-like qualities.{{citation needed|date=February 2020}} The modification of morphine and the aforementioned synthetics has also given rise to non-narcotic drugs with other uses such as emetics, stimulants, antitussives, anticholinergics, muscle relaxants, local anaesthetics, general anaesthetics, and others.{{citation needed|date=February 2020}} Morphine-derived [[agonist–antagonist]] drugs have also been developed.{{citation needed|date=February 2020}}

===Structure description===
[[File:Benzylisoquinoline structure in Morphine.svg|thumb|class=skin-invert-image|Chemical structure of morphine. The [[benzylisoquinoline]] backbone is shown in green.]]
[[File:Morphine numbered.svg|thumb|class=skin-invert-image|Morphine structure showing its standard ring lettering and carbon numbering system{{citation needed|date=February 2020}}]]
[[File:Morphine chemical structure in 3D.png|thumb|class=skin-invert-image|Same structure, but in a three-dimensional perspective]]
Morphine is a [[benzylisoquinoline]] alkaloid with two additional ring closures.<ref>{{cite book |title=Triboluminescence: Theory, Synthesis, and Application | vauthors = Olawale DO, Okoli OO, Fontenot RS, Hollerman WA |edition=illustrated |publisher=Springer |year=2016 |isbn=978-3-319-38842-7 |page=193 |url=https://books.google.com/books?id=5G6zDAAAQBAJ}} [https://books.google.com/books?id=5G6zDAAAQBAJ&pg=PA193 Extract of page 193]</ref> As Jack DeRuiter of the Department of Drug Discovery and Development (formerly, Pharmacal Sciences), Harrison School of Pharmacy, Auburn University stated in his Fall 2000 course notes for that earlier department's "Principles of Drug Action 2" course, "Examination of the morphine molecule reveals the following structural features important to its pharmacological profile...{{blockquote|
# A rigid [[pentacyclic]] structure consisting of a [[benzene]] ring (A), two partially unsaturated [[cyclohexane]] rings (B and C), a [[piperidine]] ring (D) and a [[tetrahydrofuran]] ring (E). Rings A, B and C are the [[phenanthrene]] ring system. This ring system has little conformational flexibility...
# Two hydroxyl functional groups: a C3-[[phenol]]ic [hydroxyl group] (p''K''<sub>a</sub> 9.9) and a C6-[[allyl]]ic [hydroxyl group],
# An [[ether]] linkage between E4 and E5,
# [[Saturated and unsaturated compounds|Unsaturation]] between C7 and C8,
# A basic, [tertiary]-amine function at position 17, [and]
# [Five] centers of chirality (C5, C6, C9, C13 and C14) with morphine exhibiting a high degree of stereoselectivity of analgesic action."<ref name="urlwww.auburn.edu">{{cite web |url = http://www.auburn.edu/~deruija/opioids_morphine.pdf |title = Narcotic analgesics: morphine and "peripherally modified" morphine analogs | vauthors = DeRuiter J |date = Fall 2000 |website = Principles of Drug Action 2 |publisher = Auburn University |url-status = live |archive-url = https://web.archive.org/web/20120111171903/http://www.auburn.edu/~deruija/opioids_morphine.pdf |archive-date = 11 January 2012 }}</ref>{{better source needed|date=February 2020}}{{update after|2020|2|8}}}}<!-- THIS HANDOUT FOR A COLLEGE CLASS IS NOT AN ADEQUATE SOURCE, BUT IT SOLVES THE OPENING PLAGIARISM ISSUE. PLEASE RE-DEVELOP THIS PARAGRAPH, FROM A RELIABLE, PEER-REVIEWED SECONDARY SOURCE. -->

Morphine and most of its derivatives do not exhibit optical isomerism, although some more distant relatives like the morphinan series (levorphanol, dextrorphan and the racemic parent chemical racemorphan) do,<ref>{{cite journal | vauthors = Way EL, Adler TK | title = The biological disposition of morphine and its surrogates | journal = Bulletin of the World Health Organization | volume = 27 | pages = 359–394 | date = 1962 | issue = 3 | pmid = 13999272 | pmc = 2555766 }}</ref> and as noted above stereoselectivity in vivo is an important issue.{{citation needed|date=February 2020}}

===Uses and derivatives===
Most of the licit morphine produced is used to make [[codeine]] by methylation.<ref>{{cite web|title=UNODC - Bulletin on Narcotics - 1958 Issue 3 - 005|url=https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1958-01-01_3_page006.html|access-date=11 February 2022|website=United Nations : Office on Drugs and Crime}}</ref> It is also a precursor for many drugs including [[heroin]] (3,6-diacetylmorphine), [[hydromorphone]] (dihydromorphinone), and [[oxymorphone]] (14-hydroxydihydromorphinone).<ref>{{Citation |title=Opioids |date=2012 |url=http://www.ncbi.nlm.nih.gov/books/NBK547864/ |work=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury |access-date=14 November 2023 |place=Bethesda (MD) |publisher=National Institute of Diabetes and Digestive and Kidney Diseases |pmid=31643200}}</ref> Most semi-synthetic opioids, both of the morphine and [[codeine]] subgroups, are created by modifying one or more of the following:{{citation needed|date=February 2020}}<!-- IF ONE SOURCE COVERS ALL POINTS, PLACE ONE SOURCE. IF IT DOES NOT, PLACE RTH REQUIRED SOURCES FOR EACH BULLET POINT. -->
* Halogenating or making other modifications at positions 1 or 2 on the morphine carbon skeleton.
* The methyl group that makes morphine into codeine can be removed or added back, or replaced with another functional group like ethyl and others to make codeine analogues of morphine-derived drugs and vice versa. Codeine analogues of morphine-based drugs often serve as prodrugs of the stronger drug, as in codeine and morphine, hydrocodone and hydromorphone, oxycodone and oxymorphone, nicocodeine and nicomorphine, dihydrocodeine and dihydromorphine, etc.
* Saturating, opening, or other changes to the bond between positions 7 and 8, as well as adding, removing, or modifying functional groups to these positions; saturating, reducing, eliminating, or otherwise modifying the 7–8 bond and attaching a functional group at 14 yields [[hydromorphinol]]; the oxidation of the hydroxyl group to a carbonyl and changing the 7–8 bond to single from double changes codeine into oxycodone.
* Attachment, removal or modification of functional groups to positions 3 or 6 (dihydrocodeine and related, hydrocodone, nicomorphine); in the case of moving the methyl functional group from position 3 to 6, codeine becomes [[heterocodeine]], which is 72 times stronger, and therefore six times stronger than morphine
* Attachment of functional groups or other modification at position 14 (oxymorphone, oxycodone, naloxone)
* Modifications at positions 2, 4, 5 or 17, usually along with other changes to the molecule elsewhere on the morphine skeleton. Often this is done with drugs produced by catalytic reduction, hydrogenation, oxidation, or the like, producing strong derivatives of morphine and codeine.

Many morphine derivatives can also be manufactured using [[thebaine]] or codeine as a starting material.{{citation needed|date=February 2020}} Replacement of the ''N''-methyl group of morphine with an ''N''-phenylethyl group results in a product that is 18 times more powerful than morphine in its opiate agonist potency.{{citation needed|date=February 2020}} Combining this modification with the replacement of the 6-[[hydroxyl]] with a 6-[[methylene group]] produces a compound some 1,443 times more potent than morphine, stronger than the [[Bentley compounds]] such as [[etorphine]] (M99, the Immobilon tranquilliser dart) by some measures.{{citation needed|date=February 2020}} Closely related to morphine are the opioids morphine-''N''-oxide (genomorphine), which is a pharmaceutical that is no longer in common use;{{citation needed|date=February 2020}} and pseudomorphine, an alkaloid that exists in opium, form as degradation products of morphine.{{citation needed|date=February 2020}}

<!-- The structure-activity relationship of morphine has been extensively studied. THIS SENTENCE IS MEANINGLESS WITHOUT STATEMENT OF WHAT ACTIVITY OR ACTIVITIES ARE UNDER CONSIDERATION. -->As a result of the extensive study and use of this molecule, more than 250 morphine derivatives (also counting codeine and related drugs) have been developed since the last quarter of the 19th century.{{citation needed|date=February 2020}} These drugs range from 25% the analgesic strength of codeine (or slightly more than 2% of the strength of morphine) to several thousand times the strength of morphine, to powerful opioid antagonists, including [[naloxone]] (Narcan), [[naltrexone]] (Trexan), [[diprenorphine]] (M5050, the reversing agent for the Immobilon dart) and [[nalorphine]] (Nalline).{{citation needed|date=February 2020}} Some opioid agonist-antagonists, partial agonists, and inverse agonists are also derived from morphine.{{citation needed|date=February 2020}} The receptor-activation profile of the semi-synthetic morphine derivatives varies widely and some, like [[apomorphine]] are devoid of narcotic effects.{{citation needed|date=February 2020}}

===Chemical salts of Morphine===
{{More citations needed section|date=March 2021 |talk=Need for expert attention}}
Both morphine and its hydrated form<!-- , C<span style="font-size:100%;"><sub>17</sub></span>H<span style="font-size:100%;"><sub>19</sub></span>NO<span style="font-size:100%;"><sub>3</sub></span>H<span style="font-size:100%;"><sub>2</sub></span>O, THIS TYPE OF FORMULAIC REPRESENTATION IS ALMOST MEANINGLESS HERE; YOU WISH THE READER TO TAKE THE COMPARABLE FORMULA FOR THE ANHYDRATE, DO A SUBTRACTION, AND THEN FACTOR TO DETERMINE WHETHER IT IS A MONO_ OR HIGHER ORDER HYDRATE? **JUST STATE IT.** --> are sparingly soluble in water.<ref>{{cite book| vauthors = Loftsson T |url=http://worldcat.org/oclc/1136560730|title=Drug Stability for Pharmaceutical Scientists|publisher=Elsevier Science & Technology|year=2013|pages=82|oclc=1136560730}}</ref><!-- ABSENT TEMPERATURE, THE FOLLOWING STATEMENT IS MEANINGLESS; HERE IT IS FOR USE IN PLAGIARISM CHECKING OF THIS UNSOURCED SECTION: In five liters of water, only one gram of the hydrate will dissolve. --> For this reason, pharmaceutical companies produce sulfate and [[Hydrochloride|hydrochloride salts]] of the drug, both of which are over 300 times more water-soluble than their parent molecule.{{clarify|date=February 2020}}{{citation needed|date=February 2020}} Whereas the pH of a saturated morphine hydrate solution is 8.5, the salts are acidic.{{citation needed|date=February 2020}} Since they derive from a strong acid but weak base, they are both at about pH = 5;{{clarify|date=February 2020}}{{citation needed|date=February 2020}} as a consequence, the morphine salts are mixed with small amounts of [[Sodium hydroxide|NaOH]] to make them suitable for injection.{{citation needed|date=February 2020}}<!-- <ref name="urlMorphine">{{cite web |url = http://www.emsb.qc.ca/laurenhill/science/morphine.html |title = Morphine |website = LHA Science Page |publisher = LaurenHill Academy |url-status = live |archive-url = https://web.archive.org/web/20050215094332/http://www.emsb.qc.ca/laurenhill/science/morphine.html |archive-date = 15 February 2005 }}</ref> A HIGH SCHOOL WEB PAGE IS NOT AN APPROPRIATE SOURCE FOR THIS WIDELY STUDIED, AND UBUQUITOUSLY DESCRIBED, IMPORTANT MOLECULE. THE SAME IS TRUE AT ALL OCCURRENCES. AND PRESENTING A CITATION AT END OF PARAGRAPH IS ACTUALLY WORSE THAN PRESENTING NONE AT ALL< BECAUSE IT GIVES THE IMPRESSION THAT THE MATERIAL IS ADEQUATELY SOURCED, TO THE NAIVE READER. -->

A number of salts of morphine are used, with the most common in current clinical use being the hydrochloride, sulfate, tartrate, and citrate;{{citation needed|date=February 2020}} less commonly methobromide, hydrobromide, hydroiodide, lactate, chloride, and bitartrate and the others listed below.{{citation needed|date=February 2020}} Morphine diacetate (heroin) is not a salt, but rather a further derivative,{{citation needed|date=February 2020}} see above.<ref>Heroin (morphine diacetate) is a Schedule I controlled substance, so it is not used clinically in the United States;{{citation needed|date=February 2020}} it is a sanctioned medication in the [[United Kingdom]] and in [[Canada]] and some countries in Continental Europe, its use being particularly common (nearly to the degree of the hydrochloride salt){{clarify|date=February 2020}} in the United Kingdom.{{citation needed|date=February 2020}}</ref>

Morphine meconate is a major form of the alkaloid in the poppy, as is morphine pectinate, nitrate, sulfate, and some others.{{citation needed|date=February 2020}} Like codeine, dihydrocodeine and other (especially older) opiates, morphine has been used as the salicylate salt by some suppliers and can be easily compounded, imparting the therapeutic advantage of both the opioid and the [[NSAID]];{{citation needed|date=February 2020}} multiple [[barbiturate]] salts of morphine were also used in the past, as was/is morphine valerate, the salt of the acid being the active principle of [[valerian (herb)|valerian]].{{citation needed|date=February 2020}} [[Calcium morphenate]] is the intermediate in various latex and poppy-straw methods of morphine production, more rarely sodium morphenate takes its place.{{citation needed|date=February 2020}} Morphine ascorbate and other salts such as the tannate, citrate, and acetate, phosphate, valerate and others may be present in poppy tea depending on the method of preparation.{{citation needed|date=February 2020}}<ref>Morphine valerate was one ingredient of a medication available for both oral and parenteral administration popular many years ago in Europe and elsewhere called Trivalin—not to be confused with the current, unrelated herbal preparation of the same name—which also included the valerates of [[caffeine]] and [[cocaine]].{{citation needed|date=February 2020}} A version containing codeine valerate as a fourth ingredient is distributed under the name Tetravalin.{{citation needed|date=February 2020}}</ref>

The salts listed by the [[United States Drug Enforcement Administration]] for reporting purposes, in addition to a few others, are as follows:{{citation needed|date=February 2020}}
{| class="talk collapsed collapsible"
|-
! Select salts of morphine with their [[Controlled Substances Act]] (CSA) schedule, [[Administrative Controlled Substances Code Number]] (ACSCN), and free base conversion ratio.{{clarify|date=February 2020}}{{citation needed|date=February 2020}}
|- style="text-align: left;"
|
{| class="wikitable"
|-
! Salt or drug !! [[Controlled Substances Act|CSA]] schedule !! [[Administrative Controlled Substances Code Number|ACSCN]] !! Free base conversion ratio
|-
| Morphine (base)
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 1
|-
| Morphine citrate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.81
|-
| Morphine bitartrate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.66
|-
| Morphine stearate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.51
|-
| Morphine phthalate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.89
|-
| Morphine hydrobromide
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.78
|-
| Morphine hydrobromide (2 H<sub>2</sub>O)
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.71
|-
| Morphine hydrochloride
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.89
|-
| Morphine hydrochloride (3 H<sub>2</sub>O)
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.76
|-
| Morphine acetate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.71
|-
| Morphine hydriodide (2 H<sub>2</sub>O)
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.64
|-
| Morphine lactate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.76
|-
| Morphine monohydrate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.94
|-
| Morphine meconate (5 H<sub>2</sub>O)
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.66
|-
| Morphine mucate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.57
|-
| Morphine nitrate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.82
|-
| Morphine phosphate ({{frac|1|2}} H<sub>2</sub>O)
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.73
|-
| Morphine phosphate (7 H<sub>2</sub>O)
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.73
|-
| Morphine salicylate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
|
|-
| Morphine pectinate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.778
|-
| Morphine phenylpropionate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.65
|-
| Morphine methyliodide
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.67
|-
| Morphine isobutyrate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.76
|-
| Morphine hypophosphite
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.81
|-
| Morphine sulfate (5 H<sub>2</sub>O)
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.75
|-
| Morphine tannate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
|
|-
| Morphine tartrate (3 H<sub>2</sub>O)
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.74
|-
| Morphine valerate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.74
|-
| Morphine diethylbarbiturate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.619
|-
| Morphine cyclopentylallylbarbiturate
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9300
| 0.561
|-
| Morphine diacetate
| [[Controlled Substances Act#Schedule I controlled substances|I]]
| 9200
| 0.74
|-
| Morphine methylbromide
| [[Controlled Substances Act#Schedule I controlled substances|I]]
| 9305
| 0.75
|-
| Morphine methylsulfonate
| [[Controlled Substances Act#Schedule I controlled substances|I]]
| 9306
| 0.75
|-
| Morphine-N-oxide
| [[Controlled Substances Act#Schedule I controlled substances|I]]
| 9307
| 1
|-
| Morphine-N-oxide quinate
| [[Controlled Substances Act#Schedule I controlled substances|I]]
| 9307
| 0.60
|-
| Morphine dinicotinate HCl (Nicomorphine)
| [[Controlled Substances Act#Schedule II controlled substances|II]]
| 9312
| 0.931
|}
|}

== Production ==
[[File:Alkaloids.png|thumb|upright=1.3|First generation production of alkaloids from licit latex-derived opium]]
In the [[opium poppy]], the alkaloids are bound to [[meconic acid]]. The method is to extract from the crushed plant with diluted sulfuric acid, which is a stronger acid than meconic acid, but not so strong to react with alkaloid molecules. The [[Extraction (chemistry)|extraction]] is performed in many steps (one amount of crushed plant is extracted at least six to ten times, so practically every [[alkaloid]] goes into the solution). From the solution obtained at the last extraction step, the alkaloids are precipitated by either ammonium hydroxide or sodium carbonate. The last step is purifying and separating morphine from other opium alkaloids. The somewhat similar Gregory process was developed in the United Kingdom during the Second World War, which begins with stewing the entire plant, in most cases save the roots and leaves, in plain or mildly acidified water, then proceeding through steps of concentration, extraction, and purification of alkaloids.{{Citation needed|date=January 2014}} Other methods of processing "poppy straw" (i.e., dried pods and stalks) use steam, one or more of several types of alcohol, or other organic solvents.

The poppy straw methods predominate in Continental Europe and the British Commonwealth, with the latex method in most common use in India. The latex method can involve either vertical or horizontal slicing of the unripe pods with a two-to five-bladed knife with a guard developed specifically for this purpose to the depth of a fraction of a millimetre and scoring of the pods can be done up to five times. An alternative latex method sometimes used in China in the past is to cut off the poppy heads, run a large needle through them, and collect the dried latex 24 to 48 hours later.{{Citation needed|date=January 2014}}

In India, opium harvested by licensed poppy farmers is dehydrated to uniform levels of hydration at government processing centers, and then sold to pharmaceutical companies that extract morphine from the opium. However, in Turkey and Tasmania, morphine is obtained by harvesting and processing the fully mature dry seed pods with attached stalks, called ''poppy straw''. In Turkey, a water extraction process is used, while in Tasmania, a solvent extraction process is used.{{Citation needed|date=April 2014}}

Opium poppy contains at least 50 different alkaloids, but most of them are of very low concentration. Morphine is the principal alkaloid in raw opium and constitutes roughly 8–19% of [[opium]] by dry weight (depending on growing conditions).<ref name="Jenkins AJ 2008" /> Some purpose-developed strains of poppy now produce opium that is up to 26% morphine by weight.{{Citation needed|date=January 2014}} A rough rule of thumb to determine the morphine content of pulverised dried poppy straw is to divide the percentage expected for the strain or crop via the latex method by eight or an empirically determined factor, which is often in the range of 5 to 15.{{Citation needed|date=January 2014}} The Norman strain of ''P. somniferum'', also developed in [[Tasmania]], produces down to 0.04% morphine but with much higher amounts of [[thebaine]] and [[oripavine]], which can be used to synthesise semi-synthetic opioids as well as other drugs like stimulants, emetics, opioid antagonists, anticholinergics, and smooth-muscle agents.{{Citation needed|date=January 2014}}

In the 1950s and 1960s, [[Hungary]] supplied nearly 60% of Europe's total medication-purpose morphine production. To this day, poppy farming is legal in Hungary, but poppy farms are limited by law to {{convert|2|acre|m2}}. It is also legal to sell dried poppy in flower shops for use in floral arrangements.

It was announced in 1973 that a team at the National Institutes of Health in the United States had developed a method for total synthesis of morphine, [[codeine]], and thebaine using coal tar as a starting material. A shortage in codeine-hydrocodone class cough suppressants (all of which can be made from morphine in one or more steps, as well as from codeine or thebaine) was the initial reason for the research.

Most morphine produced for pharmaceutical use around the world is actually converted into codeine as the concentration of the latter in both raw opium and poppy straw is much lower than that of morphine; in most countries, the usage of codeine (both as end-product and precursor) is at least equal or greater than that of morphine on a weight basis.

=== Chemical synthesis ===
{{Main|Morphine total synthesis}}
The first [[morphine total synthesis]], devised by [[Marshall D. Gates, Jr.]] in 1952, remains a widely used example of [[total synthesis]].<ref>{{cite journal |vauthors = Gates M, Tschudi G |title = The Synthesis of Morphine |journal = Journal of the American Chemical Society |date = April 1956 |volume = 78 |issue = 7 |pages = 1380–1393 |doi = 10.1021/ja01588a033 }}</ref> Several other syntheses were reported, notably by the research groups of Rice,<ref>{{cite journal | vauthors = Rice KC |title = Synthetic opium alkaloids and derivatives. A short total synthesis of (±)-dihydrothebainone, (±)-dihydrocodeinone, and (±)-nordihydrocodeinone as an approach to a practical synthesis of morphine, codeine, and congeners |journal = The Journal of Organic Chemistry |date = July 1980 |volume = 45 |issue = 15 |pages = 3135–3137 |doi = 10.1021/jo01303a045 }}</ref> Evans,<ref>{{cite journal |vauthors = Evans DA, Mitch CH |title = Studies directed towards the total synthesis of morphine alkaloids |journal = Tetrahedron Letters |date = January 1982 |volume = 23 |issue = 3 |pages = 285–288 |doi = 10.1016/S0040-4039(00)86810-0 }}</ref> Fuchs,<ref>{{cite journal |vauthors = Toth JE, Hamann PR, Fuchs PL |title = Studies culminating in the total synthesis of (dl)-morphine |journal = The Journal of Organic Chemistry |date = September 1988 |volume = 53 |issue = 20 |pages = 4694–4708 |doi = 10.1021/jo00255a008 }}</ref> Parker,<ref>{{cite journal |vauthors = Parker KA, Fokas D |title = Convergent synthesis of (±)-dihydroisocodeine in 11 steps by the tandem radical cyclization strategy. A formal total synthesis of (±)-morphine |journal = Journal of the American Chemical Society |date = November 1992 |volume = 114 |issue = 24 |pages = 9688–9689 |doi = 10.1021/ja00050a075 }}</ref> Overman,<ref>{{cite journal |vauthors = Hong CY, Kado N, Overman LE |title = Asymmetric synthesis of either enantiomer of opium alkaloids and morphinans. Total synthesis of (−)- and (+)-dihydrocodeinone and (−)- and (+)-morphine |journal = Journal of the American Chemical Society |date = November 1993 |volume = 115 |issue = 23 |pages = 11028–11029 |doi = 10.1021/ja00076a086 }}</ref> Mulzer-Trauner,<ref>{{cite journal |vauthors = Mulzer J, Dürner G, Trauner D |title = Formal Total Synthesis of(—)-Morphine by Cuprate Conjugate Addition |journal = Angewandte Chemie International Edition in English |date = December 1996 |volume = 35 |issue = 2324 |pages = 2830–2832 |doi = 10.1002/anie.199628301 }}</ref> White,<ref>{{cite journal |vauthors = White JD, Hrnciar P, Stappenbeck F |title = Asymmetric Total Synthesis of (+)-Codeine via Intramolecular Carbenoid Insertion |journal = The Journal of Organic Chemistry |date = October 1999 |volume = 64 |issue = 21 |pages = 7871–7884 |doi = 10.1021/jo990905z }}</ref> Taber,<ref>{{cite journal | vauthors = Taber DF, Neubert TD, Rheingold AL | title = Synthesis of (-)-morphine | journal = Journal of the American Chemical Society | volume = 124 | issue = 42 | pages = 12416–7 | date = October 2002 | pmid = 12381175 | doi = 10.1021/ja027882h | s2cid = 32048193 }}</ref> Trost,<ref>{{cite journal | vauthors = Trost BM, Tang W | title = Enantioselective synthesis of (-)-codeine and (-)-morphine | journal = Journal of the American Chemical Society | volume = 124 | issue = 49 | pages = 14542–3 | date = December 2002 | pmid = 12465957 | doi = 10.1021/ja0283394 | url = https://figshare.com/articles/Enantioselective_Synthesis_of_-Codeine_and_-Morphine/3646293 }}</ref> Fukuyama,<ref>{{cite journal | vauthors = Uchida K, Yokoshima S, Kan T, Fukuyama T | title = Total synthesis of (+/-)-morphine | journal = Organic Letters | volume = 8 | issue = 23 | pages = 5311–3 | date = November 2006 | pmid = 17078705 | doi = 10.1021/ol062112m }}</ref> Guillou,<ref>{{cite journal | vauthors = Varin M, Barré E, Iorga B, Guillou C | title = Diastereoselective total synthesis of (+/-)-codeine | journal = Chemistry: A European Journal | volume = 14 | issue = 22 | pages = 6606–8 | year = 2008 | pmid = 18561354 | doi = 10.1002/chem.200800744 }}</ref> and Stork.<ref>{{cite journal | vauthors = Stork G, Yamashita A, Adams J, Schulte GR, Chesworth R, Miyazaki Y, Farmer JJ | title = Regiospecific and stereoselective syntheses of (+/-) morphine, codeine, and thebaine via a highly stereocontrolled intramolecular 4 + 2 cycloaddition leading to a phenanthrofuran system | journal = Journal of the American Chemical Society | volume = 131 | issue = 32 | pages = 11402–6 | date = August 2009 | pmid = 19624126 | doi = 10.1021/ja9038505 | url = https://figshare.com/articles/Regiospecific_and_Stereoselective_Syntheses_of_Morphine_Codeine_and_Thebaine_via_a_Highly_Stereocontrolled_Intramolecular_4_2_Cycloaddition_Leading_to_a_Phenanthrofuran_System/2834536 }}</ref> Because of the stereochemical complexity and consequent synthetic challenge presented by this [[Polycyclic compound|polycyclic]] structure, Michael Freemantle has expressed the view that it is "highly unlikely" that a chemical synthesis will ever be cost-effective such that it could compete with the cost of producing morphine from the opium poppy.<ref>{{cite web |url = http://pubs.acs.org/cen/coverstory/83/8325/8325morphine.html |title = The Top Pharmaceuticals That Changed The World-Morphine |publisher = Chemical and Engineering News | vauthors = Freemantle M |date = 20 June 2005 }}</ref>

===GMO 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>

== Precursor to other opioids ==

=== Pharmaceutical ===
{{expand section | with = sourced content that brielfy summarises how morphine is used, industrially and globally, to produce other compounds with utility in medicine or research | small = no|date=February 2020}}
Morphine is a precursor in the manufacture in a number of opioids such as [[dihydromorphine]], [[hydromorphone]], [[hydrocodone]], and [[oxycodone]] as well as [[codeine]], which itself has a large family of semi-synthetic derivatives.<ref>{{cite web|title=Narcotics (Opioids) {{!}} DEA|url=https://www.dea.gov/taxonomy/term/331|access-date=21 January 2021|website=www.dea.gov}}</ref><!-- Morphine is commonly treated with [[acetic anhydride]] and ignited to yield heroin.<ref>{{cite book |vauthors = Small LF, Lutz RE |title = Chemistry of the Opium Alkaloids |publisher = U. S. Government Printing Office |location = Washington, D. C. |year = 1932 |pages = 153–154 |asin = B000H4LBY8 }}</ref>
Throughout Europe there is growing acceptance within the medical community of the use of slow release oral morphine as a substitution treatment alternative to methadone and buprenorphine for patients not able to tolerate the side-effects of buprenorphine and methadone. Slow-release oral morphine has been in widespread use for opiate maintenance therapy in Austria, Bulgaria, and Slovakia for many years and it is available on a small scale in many other countries including the UK. The long-acting nature of slow-release morphine mimics that of buprenorphine because the sustained blood levels are relatively flat so there is no "high" per se that a patient would feel but rather a sustained feeling of wellness and avoidance of withdrawal symptoms. For patients sensitive to the side-effects that in part may be a result of the unnatural pharmacological actions of buprenorphine and methadone, slow-release oral morphine formulations offer a promising future for use managing opiate addiction.
The pharmacology of heroin and morphine is identical except the two [[acetyl]] groups increase the [[lipophilicity|lipid solubility]] of the heroin molecule, causing heroin to cross the [[blood–brain barrier]] and enter the [[Human brain|brain]] more rapidly in injection. Once in the brain, these acetyl groups are removed to yield morphine, which causes the subjective effects of heroin. Thus, heroin may be thought of as a more rapidly acting form of morphine.<ref name="Klous 2005">{{cite journal | vauthors = Klous MG, Van den Brink W, Van Ree JM, Beijnen JH | title = Development of pharmaceutical heroin preparations for medical co-prescription to opioid dependent patients | journal = Drug and Alcohol Dependence | volume = 80 | issue = 3 | pages = 283–95 | date = December 2005 | pmid = 15916865 | doi = 10.1016/j.drugalcdep.2005.04.008 }}</ref> -->

=== Illicit ===
Illicit morphine is produced, though rarely, from codeine found in over-the-counter cough and pain medicines.{{citation needed|date=February 2020}}<!-- This demethylation reaction is often performed using pyridine and hydrochloric acid.<ref>{{cite journal |vauthors = Rapoport H, Lovell CH, Tolbert BM |title = The Preparation of Morphine-N-methyl-C<sup>14</sup> |journal = Journal of the American Chemical Society |date = December 1951 |volume = 73 |issue = 12 |pages = 5900 |doi = 10.1021/ja01156a543 }}</ref>

 --> Another illicit source is morphine extracted from extended-release morphine products<!-- , which yield a morphine solution that can be injected -->.<ref>{{cite journal | vauthors = Crews JC, Denson DD | title = Recovery of morphine from a controlled-release preparation. A source of opioid abuse | journal = Cancer | volume = 66 | issue = 12 | pages = 2642–4 | date = December 1990 | pmid = 2249204 | doi = 10.1002/1097-0142(19901215)66:12<2642::AID-CNCR2820661229>3.0.CO;2-B | doi-access = free }}</ref><!-- As an alternative, the tablets can be crushed and snorted, injected or swallowed, although this provides much less euphoria but retains some of the extended-release effect, and the extended-release property is why MS-Contin is used in some countries alongside [[methadone]], [[dihydrocodeine]], [[buprenorphine]], [[dihydroetorphine]], [[piritramide]], [[Levacetylmethadol|levo-alpha-acetylmethadol]] ([[LAAM]]), and special 24-hour formulations of [[hydromorphone]] for maintenance and detoxification of those physically dependent on opioids.

Another means of using or misusing morphine is to use --> Chemical reactions can then be used to convert morphine, dihydromorphine, and hydrocodone into [[heroin]] or other opioids [e.g., [[diacetyldihydromorphine]] (Paralaudin), and [[thebacon]]].{{citation needed|date=February 2020}}<!-- Morphine can, using a technique reported in New Zealand (where the initial precursor is codeine) and elsewhere known as home-bake, be turned into what is usually a mixture of morphine, heroin, 3-monoacetylmorphine, 6-monoacetylmorphine, and codeine derivatives like acetylcodeine if the process is using morphine made from demethylating codeine.

Since heroin is one of a series of 3,6 diesters of morphine, it is possible to convert morphine to [[nicomorphine]] (Vilan) using nicotinic anhydride, [[dipropanoylmorphine]] with propionic anhydride, dibutanoylmorphine and disalicyloylmorphine with the respective acid anhydrides. Glacial [[acetic acid]] can be used to obtain a mixture high in 6-monoacetylmorphine, [[niacin]] (vitamin B<sub>3</sub>) in some form would be precursor to 6-nicotinylmorphine, salicylic acid may yield the salicyoyl analogue of 6-MAM, and so on.

 --> Other clandestine conversions—of morphine, into ketones of the hydromorphone class, or other derivatives like [[dihydromorphine]] (Paramorfan), [[desomorphine]] (Permonid), [[metopon]], etc., and of codeine into [[hydrocodone]] (Dicodid), [[dihydrocodeine]] (Paracodin), etc. <!-- is more involved, time-consuming, requires lab equipment of various types, and usually requires expensive catalysts and large amounts of morphine at the outset and is less common but still has been discovered by authorities in various ways during the last 20 years or so. -->—require greater expertise, and types and quantities of chemicals and equipment that are more difficult to source, and so are more rarely used, illicitly (but cases have been recorded).{{citation needed|date=February 2020}}

== History ==
[[File:Friedrich Wilhelm Adam Sertuerner.jpg|thumb|[[Friedrich Sertürner]]]]

The earliest known reference to morphine can be traced back to Theophrastus in the 3rd century BC, however, possible references to morphine may go as far back as 2100 BC as Sumerian clay tablets which records lists of medical prescriptions include opium-based cures.<ref>{{cite journal | vauthors = Norn S, Kruse PR, Kruse E | title = [History of opium poppy and morphine] | journal = Dansk Medicinhistorisk Arbog | volume = 33 | pages = 171–184 | date = 2005 | pmid = 17152761 | url = https://pubmed.ncbi.nlm.nih.gov/17152761 }}</ref>

An opium-based elixir has been ascribed to [[Alchemy|alchemists]] of [[Byzantine Empire|Byzantine]] times, but the specific formula was lost during the Ottoman conquest of [[Constantinople]] ([[Istanbul]]).<ref>{{cite journal |vauthors = Ramoutsaki IA, Askitopoulou H, Konsolaki E |title = Pain relief and sedation in Roman Byzantine texts: ''Mandragoras officinarum'', ''Hyoscyamos niger'' and ''Atropa belladonna'' |journal = International Congress Series |date = December 2002 |volume = 1242 |pages = 43–50 |doi = 10.1016/S0531-5131(02)00699-4 }}</ref> Around 1522, [[Paracelsus]] made reference to an opium-based elixir that he called ''laudanum'' from the Latin word ''laudāre'', meaning "to praise". He described it as a potent painkiller, but recommended that it be used sparingly. The recipe given differs substantially from that of modern-day laudanum.<ref name="Sigerist">{{cite journal | vauthors = Sigerist HE |title=Laudanum in the Works of Paracelsus |journal=Bull. Hist. Med. |date=1941 |volume=9 |pages=530–544 |url=http://www.samorini.it/doc1/alt_aut/sz/sigerist-laudanum-in-the-work-of-paracelsus.pdf |access-date=5 September 2018}}</ref>

Morphine was discovered as the first active alkaloid extracted from the [[opium poppy]] plant in December 1804 in [[Paderborn, Germany|Paderborn]] by German pharmacist [[Friedrich Sertürner]]<ref name="pmid18443637"/>.<ref name=Luch2009 /><ref>{{cite journal | title = Friedrich Sertürner (Untitled letter to the editor) | date = 1805 | url = https://books.google.com/books?id=8A09AAAAcAAJ&pg=PA229 | archive-url = https://web.archive.org/web/20160817101928/https://books.google.com/books?id=8A09AAAAcAAJ&pg=PA229 | archive-date=17 August 2016 | journal = Journal der Pharmacie für Aerzte, Apotheker und Chemisten | trans-title = Journal of Pharmacy for Physicians, Apothecaries, and Chemists | language = de | volume = 13 | pages = 229–243; see especially "III. Säure im Opium" (acid in opium), pp. 234–235, and "I. Nachtrag zur Charakteristik der Säure im Opium" (Addendum on the characteristics of the acid in opium), pp. 236–241 }}</ref> In 1817, Sertürner reported experiments in which he administered morphine to himself, three young boys, three dogs, and a mouse; all four people almost died.<ref name=Dahan2010>{{cite journal | vauthors = Dahan A, Aarts L, Smith TW | title = Incidence, Reversal, and Prevention of Opioid-induced Respiratory Depression | journal = Anesthesiology | volume = 112 | issue = 1 | pages = 226–38 | date = January 2010 | pmid = 20010421 | doi = 10.1097/ALN.0b013e3181c38c25 | doi-access = free }}</ref> Sertürner originally named the substance ''morphium'' after the Greek god of dreams, [[Morpheus (mythology)|Morpheus]], as it has a tendency to cause sleep.<ref name=Clay2013/><ref>Sertürner coined the term ''morphium'' in: Sertuerner (1817) [https://babel.hathitrust.org/cgi/pt?id=uc1.b4433519;view=1up;seq=74 "Ueber das Morphium, eine neue salzfähige Grundlage, und die Mekonsäure, als Hauptbestandtheile des Opiums"] (On morphine, a new salifiable [i.e., precipitable], fundamental substance, and meconic acid, as principal components of opium), ''Annalen der Physik'', '''55''' : 56–89. It was [[Joseph Louis Gay-Lussac|Gay-Lussac]], a French chemist and editor of ''Annales de Chimie et de Physique'', who coined the word ''morphine'' in a French translation of Sertuener's original German article: Sertuener (1817) [https://babel.hathitrust.org/cgi/pt?id=nyp.33433062742444;view=1up;seq=29 "Analyse de l'opium: De la morphine et de l'acide méconique, considérés comme parties essentielles de l'opium"] (Analysis of opium: On morphine and on meconic acid, considered as essential constituents of opium), ''Annales de Chimie et de Physique'', 2nd series, '''5''' : 21–42. From p. 22: ''" ... car il a pris pour cette substance, que j'appelle ''morphine'' (''morphium''), ce qui n'en était qu'une combinaison avec ''l'acide de l'opium''."'' ( ... for he [i.e., French chemist and pharmacist Charles Derosne (1780–1846)] took as that substance [i.e., the active ingredient in opium], which I call "morphine" (or ''morphium''), what was only a compound of it with ''acid of opium''.)</ref> Sertürner's morphium was six times stronger than opium. He hypothesized that, because lower doses of the drug were needed, it would be less addictive. However Sertürner became addicted to the drug, warning that "I consider it my duty to attract attention to the terrible effects of this new substance I called morphium in order that calamity may be averted."<ref>{{cite journal | vauthors = Offit P |title=God's Own Medicine |journal=[[Skeptical Inquirer]] |date=March–April 2017 |volume=41 |issue=2 |page=44}}</ref>

The drug was first marketed to the general public by Sertürner and Company in 1817 as a [[analgesic|pain medication]], and also as a treatment for opium and alcohol addiction. It was first used as a poison in 1822 when [[Edme Castaing]] of France was convicted of murdering a patient.<ref>{{cite book |title = Annual Register |date = 1824 |publisher = J. Dodsley |page = [https://archive.org/details/annualregister03dodsgoog/page/n2 1] |url = https://archive.org/details/annualregister03dodsgoog |quote = Edme. |access-date = 1 September 2015 }}</ref> Commercial production began in Darmstadt, Germany, in 1827 by the pharmacy that became the pharmaceutical company Merck, with morphine sales being a large part of their early growth.<ref>{{cite book | vauthors = Kirsch DR |url=https://www.worldcat.org/oclc/966360188 |title=Drug Hunters. |date=2016 |publisher=Arcade Publishing |isbn=978-1-62872-719-7 |oclc=966360188}}</ref><ref>{{cite book |url=https://www.worldcat.org/oclc/1162209949 |title=Cocaine global histories |date=1999 |publisher=Routledge | vauthors = Gootenberg P |isbn=92-9078-018-5 |location=London |pages=90 |oclc=1162209949}}</ref> In the 1850s, [[Alexander Wood (physician)|Alexander Wood]] reported that he had injected morphine into his wife Rebecca as an experiment; the myth goes that this killed her because of respiratory depression,<ref name=Dahan2010/> but she outlived her husband by ten years.<ref>{{cite book | title= The Pursuit of Oblivion: A Global History of Narcotics| vauthors = Davenport-Hines R | page=68| publisher=W.W. Norton | year=2003 | isbn=978-0-393-32545-4}}</ref>

Later it was found that morphine was more addictive than either alcohol or opium, and its extensive use during the [[American Civil War]] allegedly resulted in over 400,000<ref>{{cite journal | vauthors = Vassallo SA |title = Lewis H. Wright Memorial Lecture |journal = ASA Newsletter |date = July 2004 |volume = 68 |issue = 7 |pages = 9–10 |url = http://www.asahq.org/For-Members/Publications-and-Research/Periodicals/ASA-Newsletter/July-2004-ASA-Newsletter.aspx |url-status = dead |archive-url = https://web.archive.org/web/20140202213600/http://www.asahq.org/For-Members/Publications-and-Research/Periodicals/ASA-Newsletter/July-2004-ASA-Newsletter.aspx |archive-date = 2 February 2014 }}</ref> people with the "soldier's disease" of morphine addiction.<ref name="urlCanadian Government Commission – Opiate Narcotics">{{cite web |url = http://www.druglibrary.org/schaffer/library/studies/ledain/nonmed4.htm |title = Opiate Narcotics |website = The Report of the Canadian Government Commission of Inquiry into the Non-Medical Use of Drugs |publisher = Canadian Government Commission |url-status = live |archive-url = https://web.archive.org/web/20070404004733/http://druglibrary.org/schaffer/Library/studies/ledain/nonmed4.htm |archive-date = 4 April 2007 }}</ref> This idea has been a subject of controversy, as there have been suggestions that such a disease was in fact a fabrication; the first documented use of the phrase "soldier's disease" was in 1915.<ref name="urlMythical Roots of US Drug Policy – Soldiers Disease and Addicts in the Civil War">{{cite web |url = http://www.druglibrary.org/schaffer/history/soldis.htm |title = Mythical Roots of US Drug Policy – Soldier's Disease and Addicts in the Civil War | vauthors = Mandel J |url-status = live |archive-url = https://web.archive.org/web/20070405235357/http://druglibrary.org/schaffer/history/soldis.htm |archive-date = 5 April 2007 }}</ref><ref name="urlSoldiers Disease A Historical Hoax?">{{cite web |url = http://www.amusingfacts.com/facts/Detail/soldiers-disease-morphine.html |title = Soldiers Disease A Historical Hoax? |year = 2006 |publisher = iPromote Media Inc |url-status = dead |archive-url = https://web.archive.org/web/20070927041927/http://www.amusingfacts.com/facts/Detail/soldiers-disease-morphine.html |archive-date = 27 September 2007 }}</ref>

Diacetylmorphine (better known as [[heroin]]) was synthesized from morphine in 1874 and brought to market by [[Bayer]] in 1898. Heroin is approximately 1.5 to 2 times more potent than morphine weight for weight. Due to the [[lipophilicity|lipid solubility]] of diacetylmorphine, it can cross the [[blood–brain barrier]] faster than morphine, subsequently increasing the reinforcing component of addiction.<ref name="pmid11961074">{{cite journal | vauthors = Winger G, Hursh SR, Casey KL, Woods JH | title = Relative reinforcing strength of three N-methyl-D-aspartate antagonists with different onsets of action | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 301 | issue = 2 | pages = 690–7 | date = May 2002 | pmid = 11961074 | doi = 10.1124/jpet.301.2.690 | s2cid = 17860947 }}</ref> Using a variety of subjective and objective measures, one study estimated the relative potency of heroin to morphine administered intravenously to post-addicts to be 1.80–2.66&nbsp;mg of morphine sulfate to 1&nbsp;mg of diamorphine hydrochloride (heroin).<ref name="martin and fraser">{{cite journal | vauthors = Martin WR, Fraser HF | title = A comparative study of physiological and subjective effects of heroin and morphine administered intravenously in postaddicts | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 133 | pages = 388–99 | date = September 1961 | pmid = 13767429 }}</ref>

[[File:MorphineAdvertisement1900 - no watermark.JPG|thumb|Advertisement for curing morphine addiction, c. 1900<ref>{{cite journal |year = 1900 |title = Morphine Easy Home Cure |journal = Overland Monthly |volume = 35 |issue = 205 |pages = 14 |url = http://quod.lib.umich.edu/m/moajrnl/ahj1472.2-35.205/22:6?page=root;rgn=full+text;size=100;view=image |url-status = live |archive-url = https://web.archive.org/web/20140201235613/http://quod.lib.umich.edu/m/moajrnl/ahj1472.2-35.205/22%3A6?page=root%3Brgn%3Dfull+text%3Bsize%3D100%3Bview%3Dimage |archive-date = 1 February 2014 }}</ref>]]
[[File:Morphine Monojet.jpg|thumb|left|An ampoule of morphine with integral needle for immediate use. Also known as a "[[syrette]]". From WWII. On display at the [[Army Medical Services Museum]].]]
Morphine became a controlled substance in the US under the [[Harrison Narcotics Tax Act]] of 1914, and possession without a prescription in the US is a criminal offense.
Morphine was the most commonly abused narcotic analgesic in the world until heroin was synthesized and came into use. In general, until the synthesis of [[dihydromorphine]] ({{circa|1900}}), the dihydromorphinone class of opioids (1920s), and [[oxycodone]] (1916) and similar drugs, there were no other drugs in the same efficacy range as opium, morphine, and heroin, with synthetics still several years away ([[pethidine]] was invented in Germany in 1937) and opioid agonists among the semi-synthetics were analogues and derivatives of codeine such as [[dihydrocodeine]] (Paracodin), [[ethylmorphine]] (Dionine), and [[benzylmorphine]] (Peronine). Even today, morphine is the most sought after prescription narcotic by heroin addicts when heroin is scarce, all other things being equal; local conditions and user preference may cause [[hydromorphone]], [[oxymorphone]], high-dose oxycodone, or [[methadone]] as well as [[dextromoramide]] in specific instances such as 1970s Australia, to top that particular list. The stop-gap drugs used by the largest absolute number of heroin addicts is probably codeine, with significant use also of [[dihydrocodeine]], poppy straw derivatives like poppy pod and poppy seed tea, [[propoxyphene]], and [[tramadol]].

The structural formula of morphine was determined by 1925 by [[Robert Robinson (organic chemist)|Robert Robinson]].<ref>{{cite journal | vauthors = Gulland JM, Robinson R |title=Constitution of codeine and thebaine |journal=Memoirs and Proceedings of the Literary and Philosophical Society of Manchester |date=1925 |volume=69 |pages=79–86}}</ref> At least three methods of total synthesis of morphine from starting materials such as coal tar and petroleum distillates have been patented, the first of which was announced in 1952, by [[Marshall D. Gates, Jr.]] at the [[University of Rochester]].<ref name="urlMarshall D. Gates, Chemist to First Synthesize Morphine, Dies : Rochester News">{{cite web |url = http://www.rochester.edu/news/show.php?id=20 | vauthors = Dickman S |title = Marshall D. Gates, Chemist to First Synthesize Morphine, Dies |date = 3 October 2003 |website = Press Release |publisher = University of Rochester |url-status = live |archive-url = https://web.archive.org/web/20101201103129/http://www.rochester.edu/news/show.php?id=20 |archive-date = 1 December 2010 }}</ref> Still, the vast majority of morphine is derived from the opium poppy by either the traditional method of gathering latex from the scored, unripe pods of the poppy, or processes using poppy straw, the dried pods and stems of the plant, the most widespread of which was invented in Hungary in 1925 and announced in 1930 by Hungarian pharmacologist [[János Kabay]].<ref>{{cite journal | vauthors = Bayer I | title = [János Kabay and the poppy straw process. Commemoration on the 50th anniversary of his death] | journal = Acta Pharmaceutica Hungarica | volume = 57 | issue = 3–4 | pages = 105–10 | date = July 1987 | pmid = 3314338 }}</ref>

In 2003, there was discovery of endogenous morphine occurring naturally in the human body. Thirty years of speculation were made on this subject because there was a receptor that, it appeared, reacted only to morphine: the [[μ-opioid receptor|μ<sub>3</sub>-opioid receptor]] in human tissue.<ref>{{cite journal | vauthors = Zhu W, Cadet P, Baggerman G, Mantione KJ, Stefano GB | title = Human white blood cells synthesize morphine: CYP2D6 modulation | journal = Journal of Immunology | volume = 175 | issue = 11 | pages = 7357–62 | date = December 2005 | pmid = 16301642 | doi = 10.4049/jimmunol.175.11.7357 | doi-access = free }}</ref> Human cells that form in reaction to cancerous [[neuroblastoma]] cells have been found to contain trace amounts of endogenous morphine.<ref name="Poeaknapo_2004" />

== Society and culture ==

=== Legal status ===
* In Australia, morphine is classified as a [[Standard for the Uniform Scheduling of Drugs and Poisons#Schedule 8 Controlled Drug (Possession without authority illegal)|Schedule 8]] drug under the variously titled State and Territory Poisons Acts.
* In Canada, morphine is classified as a [[Controlled Drugs and Substances Act#Schedule I|Schedule I]] drug under the [[Controlled Drugs and Substances Act]].
* In France, morphine is in the strictest schedule of controlled substances, based upon the December 1970 French controlled substances law.
* In Germany, morphine is a ''verkehrsfähiges und verschreibungsfähiges Betäubungsmittel'' listed under ''Anlage III'' (the equivalent of CSA Schedule II) of the [[Betäubungsmittelgesetz]].<ref>{{cite web | url = http://www.gesetze-im-internet.de/btmg_1981/anlage_iii_61.html | title = Anlage III (zu §&nbsp;1 Abs.&nbsp;1) verkehrsfähige und verschreibungsfähige Betäubungsmittel | trans-title = Appendix III (to §1 paragraph 1) marketable and prescription narcotics | language = de | work = Bundesamt für Justiz (Federal Office of Justice) | archive-url = https://web.archive.org/web/20140428231820/http://www.gesetze-im-internet.de/btmg_1981/anlage_iii_61.html | archive-date = 28 April 2014 }}</ref>
* In Switzerland, morphine is scheduled similarly to Germany's legal classification of the drug.
* In Japan, morphine is classified as a narcotic under the [[:ja:麻薬及び向精神薬取締法|Narcotics and Psychotropics Control Act]] ({{lang|ja|麻薬及び向精神薬取締法}}, ''mayaku oyobi kōseishinyaku torishimarihō'').
* In the Netherlands, morphine is classified as a List 1 drug under the [[Opium Law]].
* In New Zealand, morphine is classified as a Class B drug under the [[Misuse of Drugs Act 1975]].<ref>{{cite web|archive-date=27 January 2021|archive-url=https://web.archive.org/web/20210127113036/https://www.legislation.govt.nz/act/public/1975/0116/latest/DLM436586.html|date=13 January 2022|title=Misuse of Drugs Act 1975, sch 2|url=https://www.legislation.govt.nz/act/public/1975/0116/latest/DLM436586.html|url-status=live}}</ref>
* In the United Kingdom, morphine is listed as a Class A drug under the [[Misuse of Drugs Act 1971]] and a Schedule 2 Controlled Drug under the [[Misuse of Drugs Regulations 2001]].
* In the United States, morphine is classified as a [[Controlled Substances Act#Schedule II controlled substances|Schedule II]] controlled substance under the [[Controlled Substances Act]] under main [[Administrative Controlled Substances Code Number]]&nbsp;9300. Morphine pharmaceuticals are subject to annual manufacturing quotas; in 2017 these quotas were 35.0 [[tonnes]] of production for sale, and 27.3 tonnes of production as an intermediate, or chemical precursor, for conversion into other drugs.<ref>{{Federal Register|82|51293}}</ref> Morphine produced for use in extremely dilute formulations is excluded from the manufacturing quota.{{citation needed|date=November 2018}}
* [[United Nations|Internationally]] (UN), morphine is a Schedule I drug under the [[Single Convention on Narcotic Drugs]].<ref>{{cite journal |date = March 2011 |title = List of narcotic drugs under international control |type = PDF |edition = 50th |page = 5 |url = http://www.incb.org/documents/Narcotic-Drugs/Yellow_List/NAR_2011_YellowList_50edition_EN.pdf |journal = Yellow List |url-status = live |archive-url = https://web.archive.org/web/20141222073522/http://www.incb.org/documents/Narcotic-Drugs/Yellow_List/NAR_2011_YellowList_50edition_EN.pdf |archive-date = 22 December 2014 }}</ref>

=== Non-medical use ===
[[File:Morphine DOJ.jpg|thumb|Example of different morphine tablets]]

The euphoria, comprehensive alleviation of distress and therefore all aspects of suffering, promotion of sociability and empathy, "body high", and [[anxiolysis]] provided by narcotic drugs including the opioids can cause the use of high doses in the absence of pain for a protracted period, which can impart a craving for the drug in the user.<ref>{{Citation | vauthors = Moini J, Koenitzer J, LoGalbo A |title=Chapter 22 - The opioid epidemic |date=1 January 2021 |url=https://www.sciencedirect.com/science/article/pii/B9780323858373000194 |work=Global Emergency of Mental Disorders |pages=401–418 | veditors = Moini J, Koenitzer J, LoGalbo A |access-date=11 January 2024 |publisher=Academic Press |doi=10.1016/B978-0-323-85837-3.00019-4 |isbn=978-0-323-85837-3 |s2cid=236695938 }}</ref> As the prototype of the entire opioid class of drugs, morphine has properties that may lead to its misuse. Morphine addiction is the model upon which the current perception of addiction is based.{{medical citation needed|date=October 2015}}

Animal and human studies and clinical experience back up the contention that morphine is one of the most euphoric drugs known, and via all but the IV route heroin and morphine cannot be distinguished according to studies because heroin is a prodrug for the delivery of systemic morphine. Chemical changes to the morphine molecule yield other euphorigenics such as [[dihydromorphine]], [[hydromorphone]] (Dilaudid, Hydal), and [[oxymorphone]] (Numorphan, Opana), as well as the latter three's methylated equivalents [[dihydrocodeine]], [[hydrocodone]], and oxycodone, respectively; in addition to heroin, there are [[dipropanoylmorphine]], [[diacetyldihydromorphine]], and other members of the 3,6 morphine diester category like [[nicomorphine]] and other similar semi-synthetic opiates like [[desomorphine]], [[hydromorphinol]], etc. used clinically in many countries of the world but also produced illicitly in rare instances.{{medical citation needed|date=October 2015}}

In general, non-medical use of morphine entails taking more than prescribed or outside of medical supervision, injecting oral formulations, mixing it with unapproved potentiators such as alcohol, cocaine, and the like, or defeating the extended-release mechanism by chewing the tablets or turning into a powder for snorting or preparing injectables. The latter method can be as time-consuming and involved as traditional methods of smoking opium. This and the fact that the liver destroys a large percentage of the drug on the first pass impacts the demand side of the equation for clandestine re-sellers, as many customers are not needle users and may have been disappointed with ingesting the drug orally. As morphine is generally as hard or harder to divert than [[oxycodone]] in a lot of cases, morphine in any form is uncommon on the street, although ampoules and phials of morphine injection, pure pharmaceutical morphine powder, and soluble multi-purpose tablets are very popular where available.{{medical citation needed|date=October 2015}}

Morphine is also available in a paste that is used in the production of heroin, which can be smoked by itself or turned to a soluble salt and injected; the same goes for the penultimate products of the Kompot (Polish Heroin) and black tar processes. Poppy straw as well as opium can yield morphine of purity levels ranging from poppy tea to near-pharmaceutical-grade morphine by itself or with all of the more than 50 other alkaloids. It also is the active narcotic ingredient in opium and all of its forms, derivatives, and analogues as well as forming from breakdown of heroin and otherwise present in many batches of illicit heroin as the result of incomplete acetylation.{{medical citation needed|date=October 2015}}

=== Names ===
Morphine is [[marketing|marketed]] under many different brand names in various parts of the world.<ref name="drugs.com-page">{{cite web | url = https://www.drugs.com/international/morphine.html | work = Drugs.com | title = International listings for Morphine | archive-url = https://web.archive.org/web/20150614052020/http://www.drugs.com/international/morphine.html | archive-date=14 June 2015 | access-date = 2 June 2015 }}</ref> It was formerly called Morphia in British English.<ref name="Morphia"/>

Informal names for morphine include: Cube Juice, Dope, Dreamer, Emsel, First Line, God's Drug, Hard Stuff, Hocus, Hows, Lydia, Lydic, M, Miss Emma, Mister Blue, Monkey, Morf, Morph, Morphide, Morphie, Morpho, Mother, MS, Ms. Emma, Mud, New Jack Swing (if mixed with [[heroin]]), Sister, Tab, Unkie, Unkie White, and Stuff.<ref>{{cite book |url = https://books.google.com/books?id=G7As-qawdzMC&q=happy+powder&pg=PA95 |title = The Encyclopedia of Addictive Drugs | vauthors = Miller RL |date = 1 January 2002 |publisher = [[Greenwood Publishing Group]] |isbn = 978-0-313-31807-8 |page = 306 }}</ref>

MS Contin tablets are known as misties, and the 100&nbsp;mg extended-release tablets as greys and blockbusters. The "[[speedball (drug)|speedball]]" can use morphine as the opioid component, which is combined with cocaine, [[amphetamines]], [[methylphenidate]], or similar drugs. "Blue Velvet" is a combination of morphine with the antihistamine [[tripelennamine]] (Pyrabenzamine, PBZ, Pelamine) taken by injection.

=== Access in developing countries ===
Although morphine is cheap, people in poorer countries often do not have access to it. According to a 2005 estimate by the [[International Narcotics Control Board]], six countries (Australia, Canada, France, Germany, the United Kingdom, and the United States) consume 79% of the world's morphine. The less affluent countries, accounting for 80% of the world's population, consumed only about 6% of the global morphine supply.<ref>{{cite book | vauthors = Milani B |title = Scholten |publisher = World Health Organization |location = Switzerland |pages = 1–22 |edition = 3rd |url = http://apps.who.int/medicinedocs/en/d/Js18062en/ |access-date = 17 January 2018 |url-status = dead |archive-url = https://web.archive.org/web/20180605033251/http://apps.who.int/medicinedocs/en/d/Js18062en/ |archive-date = 5 June 2018 }}</ref> Some countries{{which|date=June 2017}} import virtually no morphine, and in others{{which|date=June 2017}} the drug is rarely available even for relieving severe pain while dying.<ref>{{cite web | author = Human Rights Watch |title=Global State of Pain Treatment; Access to Palliative Care as a Human Right |date=2 June 2011 |url=https://www.hrw.org/report/2011/06/02/global-state-pain-treatment/access-medicines-and-palliative-care#_ftn22 |publisher=Human Rights Watch |access-date=27 January 2020 |ref=p.1-3}}</ref>

Experts in pain management attribute the under-distribution of morphine to an unwarranted fear of the drug's potential for addiction and abuse. While morphine is clearly addictive, Western doctors believe it is worthwhile to use the drug and then wean the patient off when the treatment is over.<ref>{{cite news | vauthors = McNeil Jr DG |title = Drugs Banned, Many of World's Poor Suffer in Pain |url = https://www.nytimes.com/2007/09/10/health/10pain.html |newspaper = [[The New York Times]] |date = 10 September 2007 |access-date = 11 September 2007 |url-status = live |archive-url = https://web.archive.org/web/20230512162123/https://www.nytimes.com/2007/09/10/health/10pain.html |archive-date = 12 May 2023 }}</ref>

== References ==
{{Reflist}}

== External links ==
{{Commons}}
* {{cite web | title=Morphine Injection | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a601161.html }}
* {{cite web | title=Morphine Rectal | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a606006.html }}

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[[Category:Morphine| ]]
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