Buprenorphine: Difference between revisions

{{Short description|Opioid used to treat pain & opioid use disorder}}

{{Distinguish|Bupropion}}

<!-- Both are often called "BUP" and both are often used with NTX (naltrexone), including in FDCs in both cases, *but for different indications*. Confusion among patients should be expected, given such sloppy ambiguous notation. -->

{{Use dmy dates|date=August 2023}}

{{Use American English|date=December 2017}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 457118559

| image = Buprenorphine.svg

| width = 220

| alt = Skeletal formula of buprenorphine

| image2 = Buprenorphine molecule from xtal ball.png

| width2 = 220

| alt2 = Ball-and-stick model of the buprenorphine molecule

| caption =

<!-- Clinical data -->

| pronounce = bew-pre-nor-feen

| tradename = Subutex, Sublocade, Brixadi, others

| Drugs.com = {{drugs.com|monograph|buprenorphine-hydrochloride}}

| MedlinePlus = a605002

| DailyMedID = Buprenorphine

| pregnancy_AU = C

| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Buprenorphine Use During Pregnancy | website=Drugs.com | date=14 October 2019 | url=https://www.drugs.com/pregnancy/buprenorphine.html | access-date=17 May 2020 | archive-date=10 November 2020 | archive-url=https://web.archive.org/web/20201110201941/https://www.drugs.com/pregnancy/buprenorphine.html | url-status=live }}</ref><ref name="Buprenorphine AusPAR">{{cite report |title=Australian Public Assessment Report for Buprenorphine |url=https://www.tga.gov.au/sites/default/files/auspar-buprenorphine-191106.pdf |publisher=[[Therapeutic Goods Administration]] |date=November 2019 |archive-url=https://web.archive.org/web/20240320144416/https://www.tga.gov.au/sites/default/files/auspar-buprenorphine-191106.pdf |archive-date=20 March 2024 |url-status=live}}</ref>

| pregnancy_category =

| dependency_liability = [[Psychological dependence|Psychological]]: High [[Physical dependence|Physical]]: Moderate<ref>{{cite book |vauthors=Bonewit-West K, Hunt AS, Applegate E |title=Today's Medical Assistant: Clinical and Administrative Procedures |date=2012 |page=571 |publisher=Elsevier Health Sciences |isbn=9781455701506 |url=https://books.google.com/books?id=YalYPI1KqTQC&pg=PA571 |access-date=16 February 2020 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110030031/https://books.google.com/books?id=YalYPI1KqTQC&pg=PA571 |url-status=live }}</ref>

| addiction_liability =

| routes_of_administration = [[Sublingual|Under the tongue]], [[Buccal administration|through the cheek]], [[intramuscular]], [[intravenous]], [[transdermal]], [[intranasal]], [[Rectal administration|rectally]], [[oral administration|by mouth]], [[Subcutaneous administration|subcutaneous]]

| class =

| ATC_prefix = N02

| ATC_suffix = AE01

| ATC_supplemental = {{ATC|N07|BC01}}

<!-- Legal status -->

| legal_AU = S8

| legal_AU_comment = <ref name="Buprenorphine AusPAR" />

| legal_BR = A1

| legal_BR_comment = <ref>{{cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023}}</ref>

| legal_CA = Schedule I

| legal_CA_comment = <ref>{{cite web |title= ARCHIVED - Report Stakeholder Workshop on a National Buprenorphine Program |url=https://www.canada.ca/en/health-canada/services/drugs-health-products/reports-publications/drug-products/report-stakeholder-workshop-national-buprenorphine-program-november-18-2004-health-canada.html |website=[[Health Canada]] |access-date=10 January 2020 |date=6 December 2004 |archive-date=26 March 2020 |archive-url=https://web.archive.org/web/20200326042128/https://www.canada.ca/en/health-canada/services/drugs-health-products/reports-publications/drug-products/report-stakeholder-workshop-national-buprenorphine-program-november-18-2004-health-canada.html |url-status=live }}</ref><ref>{{cite web | title= Neurological therapies | website=[[Health Canada]] | date=9 May 2018 | url=https://www.canada.ca/en/services/health/drug-health-products/drug-medical-device-highlights-2017/approved-drugs/neurological-therapies.html | access-date=13 April 2024}}</ref>

| legal_DE = Anlage III

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = Class C

| legal_UK_comment =

| legal_US = Schedule III

| legal_US_comment = <ref>{{cite web | title=Subutex (buprenorphine sublingual tablets), CIII Initial U.S. Approval: 1981 | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=660696 | access-date=26 May 2023 | archive-date=27 May 2023 | archive-url=https://web.archive.org/web/20230527012727/https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=660696 | url-status=live }}</ref><ref>{{cite web | title=Sublocade- buprenorphine solution | website=DailyMed | date=15 March 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6189fb21-9432-45f8-8481-0bfaf3ccde95 | access-date=26 May 2023 | archive-date=27 May 2023 | archive-url=https://web.archive.org/web/20230527012729/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6189fb21-9432-45f8-8481-0bfaf3ccde95 | url-status=live }}</ref><ref>{{cite web | title=Butrans- buprenorphine patch, extended release | website=DailyMed | date=26 June 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=794aa355-66de-41b8-aedf-f2c40f6bc664 | access-date=26 May 2023 | archive-date=27 May 2023 | archive-url=https://web.archive.org/web/20230527015432/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=794aa355-66de-41b8-aedf-f2c40f6bc664 | url-status=live }}</ref><ref name="Brixadi FDA label">{{cite web | title=Brixadi- buprenorphine injection | website=DailyMed | date=21 June 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d8a8fd0-8619-422a-a664-d1d2e8970f48 | access-date=25 June 2023 | archive-date=26 June 2023 | archive-url=https://web.archive.org/web/20230626054011/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d8a8fd0-8619-422a-a664-d1d2e8970f48 | url-status=live }}</ref><ref>{{cite press release | title=FDA Approves New Buprenorphine Treatment Option for Opioid Use Disorder | website=U.S. Food and Drug Administration | date=23 May 2023 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-buprenorphine-treatment-option-opioid-use-disorder | access-date=26 May 2023}}</ref>

| legal_EU = Rx-only

| legal_EU_comment =

| legal_UN = P III <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->| bioavailability = Sublingual: 30%<ref name="pmid9048270">{{cite journal | vauthors = Mendelson J, Upton RA, Everhart ET, Jacob P, Jones RT | title = Bioavailability of sublingual buprenorphine | journal = Journal of Clinical Pharmacology | volume = 37 | issue = 1 | pages = 31–37 | date = January 1997 | pmid = 9048270 | doi = 10.1177/009127009703700106 | s2cid = 31735116 }}</ref><br />Intranasal: 48%<ref name="pmid2576057">{{cite journal | vauthors = Eriksen J, Jensen NH, Kamp-Jensen M, Bjarnø H, Friis P, Brewster D | title = The systemic availability of buprenorphine administered by nasal spray | journal = The Journal of Pharmacy and Pharmacology | volume = 41 | issue = 11 | pages = 803–805 | date = November 1989 | pmid = 2576057 | doi = 10.1111/j.2042-7158.1989.tb06374.x | s2cid = 1286222 }}</ref><br />Buccal: 65%<ref>{{cite web|url=https://www.pbm.va.gov/PBM/clinicalguidance/abbreviatedreviews/Buprenorphine_NX_Buccal_Film_BUNAVAIL_%20Abbreviated_Review.pdf|title=Buprenorphine / Naloxone Buccal Film (BUNAVAIL) C-III|date=September 2014|website=Pharmacy Benefits Management (PBM) Services|access-date=10 February 2020|archive-date=20 October 2020|archive-url=https://web.archive.org/web/20201020045302/https://www.pbm.va.gov/PBM/clinicalguidance/abbreviatedreviews/Buprenorphine_NX_Buccal_Film_BUNAVAIL_%20Abbreviated_Review.pdf|url-status=live}}</ref><ref name="BUNAVAIL_prescribing_information">{{cite web | title=Bunavail (buprenorphine and naloxone buccal film), CIII Initial U.S. Approval: 2002 | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=657905 | access-date=26 May 2023 | archive-date=27 May 2023 | archive-url=https://web.archive.org/web/20230527012731/https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=657905 | url-status=live }}</ref>

| protein_bound = 96%

| metabolism = [[Liver]] ([[CYP3A4]], [[CYP2C8]])

| metabolites =

| onset = Within 30 min<ref name=ASHP2017/>

| elimination_half-life = 37 hours (range 20–70 hours)

| duration_of_action = Up to 24 hrs<ref name=ASHP2017/>

| excretion = [[Bile duct]] and [[kidney]]

<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 52485-79-7

| CAS_supplemental =

| PubChem = 644073

| IUPHAR_ligand = 1670

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00921

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 559124

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 40D3SCR4GZ

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D07132

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 3216

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 511142

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = <!-- Chemical and physical data -->

| IUPAC_name = (2''S'')-2-[(5''R'',6''R'',7''R'',14''S'')-17-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl]-3,3-dimethylbutan-2-ol

| C = 29

| H = 41

| N = 1

| O = 4

| SMILES = Oc7ccc5c1c7O[C@H]3[C@]6(OC)[C@H](C[C@@]2([C@H](N(CC[C@@]123)CC4CC4)C5)CC6)[C@@](O)(C)C(C)(C)C

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C29H41NO4/c1-25(2,3)26(4,32)20-15-27-10-11-29(20,33-5)24-28(27)12-13-30(16-17-6-7-17)21(27)14-18-8-9-19(31)23(34-24)22(18)28/h8-9,17,20-21,24,31-32H,6-7,10-16H2,1-5H3/t20-,21-,24-,26+,27-,28+,29-/m1/s1

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = RMRJXGBAOAMLHD-IHFGGWKQSA-N

| density =

| density_notes =

| melting_point =

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

<!-- Definition and medical uses -->

'''Buprenorphine''', sold under the brand name '''Subutex''' among others, is an [[opioid]] used to treat [[opioid addiction|opioid use disorder]], acute [[pain]], and [[chronic pain]].<ref name=ASHP2017/> It can be used [[sublingual|under the tongue (sublingual)]], [[buccal administration|in the cheek (buccal)]], by [[Injection (medicine)|injection]] ([[intravenous]] and [[Subcutaneous administration|subcutaneous]]), as a [[transdermal patch|skin patch (transdermal)]], or as an [[medical implant|implant]].<ref name=ASHP2017/><ref>{{cite press release |title=FDA approves first buprenorphine implant for treatment of opioid dependence |url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-buprenorphine-implant-treatment-opioid-dependence |website=U.S. Food and Drug Administration|date=26 May 2016|access-date=12 December 2017|archive-date=30 November 2017|archive-url=https://web.archive.org/web/20171130112207/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm503719.htm|url-status=live}}</ref> For opioid use disorder, the patient must have moderate opioid withdrawal symptoms before buprenorphine can be administered under direct observation of a health-care provider.<ref name=ASHP2017/>

In the United States, the combination formulation of [[buprenorphine/naloxone]] (Suboxone) is usually prescribed to discourage misuse by injection.<ref name=ASHP2017/> However, more recently the efficacy of naloxone in preventing misuse has been brought into question, and preparations of buprenorphine combined with naloxone could potentially be less safe than buprenorphine alone.<ref name=reconsidering2020>{{cite journal | vauthors = Blazes CK, Morrow JD | title = Reconsidering the Usefulness of Adding Naloxone to Buprenorphine | journal = Frontiers in Psychiatry | volume = 11 | pages = 549272 | date = 11 September 2020 | pmid = 33061915 | doi = 10.3389/fpsyt.2020.549272 | pmc = 7517938 | doi-access = free }}</ref> Maximum pain relief is generally within an hour with effects up to 24 hours.<ref name=ASHP2017/> Buprenorphine affects different types of [[opioid receptors]] in different ways.<ref name="ASHP2017" /> Depending on the type of [[opioid receptor]], it may be an [[agonist]], [[partial agonist]], or [[Receptor antagonist|antagonist]].<ref name="ASHP2017" /> Buprenorphine's activity as an agonist/antagonist is important in the treatment of opioid use disorder: it relieves withdrawal symptoms from other opioids and induces some euphoria, but also blocks the ability for many other opioids, including heroin, to cause an effect. Unlike full agonists like heroin or methadone, buprenorphine has a ceiling effect, such that taking more medicine past a certain point will not increase the effects of the drug.<ref name="pmid22346191">{{cite journal | vauthors = Whelan PJ, Remski K | title = Buprenorphine vs methadone treatment: A review of evidence in both developed and developing worlds | journal = Journal of Neurosciences in Rural Practice | volume = 3 | issue = 1 | pages = 45–50 | date = January 2012 | pmid = 22346191 | pmc = 3271614 | doi = 10.4103/0976-3147.91934 | doi-access = free }}</ref>

<!-- Side effects and mechanism -->

Side effects may include [[respiratory depression]] (decreased breathing), sleepiness, [[adrenal insufficiency]], [[QT prolongation]], [[hypotension|low blood pressure]], [[allergic reaction]]s, [[constipation]], and opioid addiction.<ref name=ASHP2017/><ref>{{cite web|title=Buprenorphine|date=15 June 2015|publisher=The Substance Abuse and Mental Health Services Administration|url=https://www.samhsa.gov/medication-assisted-treatment/medications-counseling-related-conditions/buprenorphine|access-date=14 October 2020|archive-date=26 August 2020|archive-url=https://web.archive.org/web/20200826213906/https://www.samhsa.gov/medication-assisted-treatment/medications-counseling-related-conditions/buprenorphine|url-status=live}}</ref> Among those with a history of [[seizures]], a risk exists of further seizures.<ref name=ASHP2017/> [[Opioid withdrawal]] following stopping buprenorphine is generally less severe than with other opioids.<ref name=ASHP2017/> Whether use during [[pregnancy]] is safe is unclear, but use while [[breastfeeding]] is probably safe, since the dose the infant receives is 1-2% that of the maternal dose, on a weight basis.<ref>{{cite web |url= https://www.drugs.com/breastfeeding/buprenorphine.html |title=Buprenorphine use while Breastfeeding |website=Drugs.com |access-date=7 February 2021 |archive-date=10 November 2020 |archive-url= https://web.archive.org/web/20201110125323/https://www.drugs.com/breastfeeding/buprenorphine.html |url-status=live}}</ref><ref name=ASHP2017/>

<!-- History and culture -->

Buprenorphine was patented in 1965, and approved for medical use in the United States in 1981.<ref name=ASHP2017>{{cite web|title=Buprenorphine Hydrochloride|url=https://www.drugs.com/monograph/buprenorphine-hydrochloride.html|website=drugs.com|publisher=American Society of Health-System Pharmacists|access-date=17 March 2017|date=26 January 2017|archive-date=18 July 2017|archive-url=https://web.archive.org/web/20170718164516/https://www.drugs.com/monograph/buprenorphine-hydrochloride.html|url-status=live}}</ref><ref name=Fis2006>{{cite book |vauthors=Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=528 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA528 |access-date=29 May 2020 |archive-date=10 January 2023 |archive-url=https://web.archive.org/web/20230110212258/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA528 |url-status=live }}</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 addition to prescription as an analgesic it is a common medication used to treat opioid use disorders, such as addiction to [[heroin]].<ref name="DEA2019" /> In 2020, it was the 186th most commonly prescribed medication in the United States, with more than 2.8{{nbsp}}million prescriptions.<ref>{{cite web | title = The Top 300 of 2020 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date = 7 October 2022 | archive-date = 12 February 2021 | archive-url = https://web.archive.org/web/20210212142534/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status = live }}</ref><ref>{{cite web | title = Buprenorphine - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Buprenorphine | access-date = 7 October 2022 | archive-date = 11 October 2022 | archive-url = https://web.archive.org/web/20221011050244/https://clincalc.com/DrugStats/Drugs/Buprenorphine | url-status = live }}</ref> Buprenorphine may also be used recreationally for the [[euphoria|high]] it can produce.<ref name=DEA2019/> In the United States, buprenorphine is a [[Controlled Substances Act#Schedule III controlled substances|schedule III]] [[controlled substance]].<ref name="DEA2019">{{cite web |date=July 2019 |title=Buprenorphine |url= https://www.samhsa.gov/medication-assisted-treatment/medications-counseling-related-conditions/buprenorphine |url-status=live |archive-url=https://web.archive.org/web/20200820141229/https://www.samhsa.gov/medication-assisted-treatment/medications-counseling-related-conditions/buprenorphine |archive-date=20 August 2020 |access-date=9 January 2020|website=SAMHSA Center for Substance Abuse Treatment (CSAT)}}</ref>

{{TOC limit}}

==Medical uses==

===Opioid use disorder===

[[File:Butrans10mcg.jpeg|thumb|left|Buprenorphine patches in the pouch with packaging: A removed patch is shown on the left. In Britain, buprenorphine patches are named Butec 5, Butec 10, and so on.]]

Buprenorphine is used to treat people with [[opioid addiction|opioid use disorder]].<ref name="ASHP2017" /><ref name="Levounis_2018">{{cite book | vauthors = Levounis P, Avery J | chapter = Patient Assessment | veditors = Renner Jr JA, Levounis P, LaRose AT |title=Office-based buprenorphine treatment of opioid use disorder |publisher=American Psychiatric Association Publishing |year=2018 |isbn=978-1-61537-170-9 |location=Arlington, VA |oclc=1002302926 }}</ref>{{Rp|84–7}} In the U.S., the combination formulation of [[buprenorphine/naloxone]] is generally prescribed to deter injection, since [[naloxone]], an opioid antagonist, is believed to cause acute withdrawal if the formulation is crushed and injected.<ref name="ASHP2017" /><ref name="Restrepo_2018">{{cite book | vauthors = Restrepo R, Levounis P | chapter = Clinical Use of Buprenorphine | veditors = Renner Jr JA, Levounis P, LaRose AT |title=Office-based buprenorphine treatment of opioid use disorder |publisher=American Psychiatric Association Publishing|year=2018|isbn=978-1-61537-170-9 |location=Arlington, VA |oclc=1002302926 }}</ref>{{Rp|99}} Taken orally, the naloxone has virtually no effect, due to the drug's extremely high [[first-pass metabolism]] and low [[bioavailability]] (2%).<ref name=AHFS2015>{{cite web|title=Naloxone Hydrochloride|url=https://www.drugs.com/monograph/naloxone-hydrochloride.html|publisher=The American Society of Health-System Pharmacists|access-date=2 January 2015|url-status=live|archive-url=https://web.archive.org/web/20150102115454/http://www.drugs.com/monograph/naloxone-hydrochloride.html|archive-date=2 January 2015}}</ref> However, the efficacy of naloxone in preventing misuse by injection has more recently been brought into question and preparations including naloxone could even be less safe than preparations containing solely buprenorphine. Anecdotally, posters on drug-related online forums have stated that they were able to attain a high by injecting preparations of buprenorphine despite being combined with naloxone.<ref name="reconsidering2020"></ref>

Before starting buprenorphine, individuals are generally advised to wait long enough after their last dose of opioid until they have some withdrawal symptoms to allow for the medication to bind the receptors, since if taken too soon, buprenorphine can displace other opioids bound to the receptors and precipitate an acute withdrawal. The dose of buprenorphine is then adjusted until symptoms improve, and individuals remain on a maintenance dose of 8–16&nbsp;mg.<ref name="Restrepo_2018" />{{Rp|99–100}}<ref name="SAM2016" /> Because withdrawal is uncomfortable and a deterrent for many patients, many have begun to call for different means of treatment initiation.<ref>{{cite journal | vauthors = Sue KL, Cohen S, Tilley J, Yocheved A | title = A Plea From People Who Use Drugs to Clinicians: New Ways to Initiate Buprenorphine Are Urgently Needed in the Fentanyl Era | journal = Journal of Addiction Medicine | volume = 16 | issue = 4 | pages = 389–391 | date = January 2022 | pmid = 35020693 | doi = 10.1097/ADM.0000000000000952 | s2cid = 245925947 }}</ref> Some providers have begun to use the Bernese method, also known as microdosing, in which very small doses of buprenorphine are given while patients are still using street opioids, and without precipitating withdrawal, with medicine levels slowly titrated upward.<ref>{{cite journal | vauthors = Hämmig R, Kemter A, Strasser J, von Bardeleben U, Gugger B, Walter M, Dürsteler KM, Vogel M | title = Use of microdoses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method | journal = Substance Abuse and Rehabilitation | volume = 7 | pages = 99–105 | date = 20 July 2016 | pmid = 27499655 | pmc = 4959756 | doi = 10.2147/SAR.S109919 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ahmed S, Bhivandkar S, Lonergan BB, Suzuki J | title = Microinduction of Buprenorphine/Naloxone: A Review of the Literature | journal = The American Journal on Addictions | volume = 30 | issue = 4 | pages = 305–315 | date = July 2021 | pmid = 33378137 | doi = 10.1111/ajad.13135 | s2cid = 229721826 }}</ref>

====Buprenorphine versus methadone====

Both buprenorphine and [[methadone]] are medications used for detoxification and [[opioid replacement therapy]], and appear to have similar effectiveness based on limited data.<ref>{{cite journal | vauthors = Gowing L, Ali R, White JM, Mbewe D | title = Buprenorphine for managing opioid withdrawal | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 2 | pages = CD002025 | date = February 2017 | pmid = 28220474 | pmc = 6464315 | doi = 10.1002/14651858.CD002025.pub5 }}</ref> Both are safe for pregnant women with opioid use disorder,<ref name="Restrepo_2018" />{{Rp|101}}<ref name="SAM2016" /> although preliminary evidence suggests that methadone is more likely to cause [[neonatal abstinence syndrome]].<ref>{{cite journal | vauthors = Lemon LS, Caritis SN, Venkataramanan R, Platt RW, Bodnar LM | title = Methadone Versus Buprenorphine for Opioid Use Dependence and Risk of Neonatal Abstinence Syndrome | language = en-US | journal = Epidemiology | volume = 29 | issue = 2 | pages = 261–268 | date = March 2018 | pmid = 29112519 | pmc = 5792296 | doi = 10.1097/EDE.0000000000000780 | quote = Methadone is associated with increased risk of neonatal abstinence syndrome compared with buprenorphine in infants exposed ''in utero''. This association is subject to minimal bias due to unmeasured confounding by severity of addiction. }}</ref> In the US and European Union, only designated clinics can prescribe methadone for opioid use disorder, requiring patients to travel to the clinic daily. If patients are drug free for a period they may be permitted to receive "take home doses," reducing their visits to as little as once a week. Alternatively, up to a month's supply of buprenorphine has been able to be prescribed by clinicians in the US or Europe who have completed a basic training (8–24 hours in the US) and received a waiver/licence allowing prescription of the medicine.<ref name="Levounis_2018" />{{Rp|84–5}} In France, buprenorphine prescription for opioid use disorder has been permitted without any special training or restrictions since 1995, resulting in treatment of approximately ten times more patients per year with buprenorphine than with methadone in the following decade.<ref>{{cite journal | vauthors = Auriacombe M, Fatséas M, Dubernet J, Daulouède JP, Tignol J | title = French field experience with buprenorphine | journal = The American Journal on Addictions | volume = 13 | issue = Suppl 1 | pages = S17–S28 | date = 2004 | pmid = 15204673 | doi = 10.1080/10550490490440780 }}</ref> In 2021, seeking to address record levels of opioid overdose, the United States also removed the requirement for a special waiver for prescribing physicians.<ref>{{cite web | author = Office of the Assistant Secretary for Health (OASH)|date=14 January 2021|title=HHS Expands Access to Treatment for Opioid Use Disorder |url= https://www.hhs.gov/about/news/2021/01/14/hhs-expands-access-to-treatment-for-opioid-use-disorder.html |access-date=5 January 2022|website=HHS.gov|archive-date=25 January 2022|archive-url=https://web.archive.org/web/20220125001024/https://www.hhs.gov/about/news/2021/01/14/hhs-expands-access-to-treatment-for-opioid-use-disorder.html|url-status=live}}</ref> Whether this change will be sufficient to impact prescription is unclear, since even before the change as many as half of physicians with a waiver permitting them to prescribe buprenorphine did not do so, and one third of non-waivered physicians reported that nothing would induce them to prescribe buprenorphine for opioid use disorder.<ref>{{cite journal | title = Removing The X-Waiver Is One Small Step Toward Increasing Treatment Of Opioid Use Disorder, But Great Leaps Are Needed | journal = Health Affairs Forefront | url = https://www.healthaffairs.org/do/10.1377/forefront.20210419.311749/full/ | access-date = 5 January 2022 | vauthors = Stringfellow EJ, Humphreys K, Jalali MS | year = 2021 | doi = 10.1377/forefront.20210419.311749 | archive-date = 14 October 2022 | archive-url = https://web.archive.org/web/20221014051149/https://www.healthaffairs.org/do/10.1377/forefront.20210419.311749/full/ | url-status = live }}</ref>

===Chronic pain===

A [[transdermal patch]] is available for the treatment of chronic pain.<ref name=ASHP2017/> These patches are not indicated for use in acute pain, pain that is expected to last only for a short period of time, or pain after surgery, nor are they recommended for opioid addiction.<ref>{{cite web|title=Butrans Medication Guide|url=http://app.purduepharma.com/xmlpublishing/pi.aspx?id=b&medguide=1|website=Butrans Medication Guide|publisher=Purdue Pharma L.P.|access-date=7 July 2014|archive-date=14 July 2014|archive-url=https://web.archive.org/web/20140714150342/http://app.purduepharma.com/xmlpublishing/pi.aspx?id=b&medguide=1|url-status=live}}</ref>

===Potency===

With respect to [[equianalgesic]] dosing, when used sublingually, the potency of buprenorphine is about 40 to 70 times that of morphine.<ref name=Cote2014/><ref>"{{cite book | chapter-url = http://www.dea.gov/pubs/abuse/4-narc.htm | chapter = Ch. 4 Narcotics: Narcotics Treatment Drugs: Buprenorphine | title = Drugs of Abuse | author = Drug Enforcement Administration | publisher = U.S. Department of Justice | date = 2005 | archive-url = https://web.archive.org/web/20061102144614/http://www.dea.gov/pubs/abuse/4-narc.htm | archive-date = 2 November 2006 }}</ref><ref>{{cite web|url=https://ww2.health.wa.gov.au/~/media/Files/Corporate/general%20documents/Health%20Networks/WA%20Cancer%20and%20Palliative%20Care/How-to-use-the-Opioid-Conversion-Guide.pdf|title=Opioid Conversion Guide|date=February 2016|website=Department of Health, Government of Western Australia|access-date=10 February 2020|archive-date=18 April 2020|archive-url=https://web.archive.org/web/20200418072615/https://ww2.health.wa.gov.au/~/media/Files/Corporate/general%20documents/Health%20Networks/WA%20Cancer%20and%20Palliative%20Care/How-to-use-the-Opioid-Conversion-Guide.pdf|url-status=live}}</ref> When used as a transdermal patch, the potency of buprenorphine may be 100 to 115 times that of morphine.<ref name=Cote2014>{{cite journal | vauthors = Cote J, Montgomery L | title = Sublingual buprenorphine as an analgesic in chronic pain: a systematic review | journal = Pain Medicine | volume = 15 | issue = 7 | pages = 1171–1178 | date = July 2014 | pmid = 24995716 | doi = 10.1111/pme.12386 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Khanna IK, Pillarisetti S | title = Buprenorphine - an attractive opioid with underutilized potential in treatment of chronic pain | journal = Journal of Pain Research | volume = 8 | pages = 859–870 | date = 2015 | pmid = 26672499 | pmc = 4675640 | doi = 10.2147/JPR.S85951 | doi-access = free }}</ref>

==Adverse effects==

[[File:Rational scale to assess the harm of drugs (mean physical harm and mean dependence).svg|thumb|upright=1.3|A 2007 assessment of harm from recreational drug use (mean physical harm and mean dependence liability): Buprenorphine was ranked 9th in dependence, 8th in physical harm, and 11th in social harm.<ref>{{cite journal | vauthors = Nutt D, King LA, Saulsbury W, Blakemore C | title = Development of a rational scale to assess the harm of drugs of potential misuse | journal = Lancet | volume = 369 | issue = 9566 | pages = 1047–1053 | date = March 2007 | pmid = 17382831 | doi = 10.1016/S0140-6736(07)60464-4 | s2cid = 5903121 }}</ref>]]

Common [[adverse drug reaction]]s associated with the use of buprenorphine, similar to those of other opioids, include nausea and vomiting, drowsiness, dizziness, headache, memory loss, cognitive and neural inhibition, perspiration, itchiness, dry mouth, shrinking of the pupils of the eyes ([[miosis]]), [[orthostatic hypotension]], male ejaculatory difficulty, decreased libido, and [[urinary retention]]. [[Constipation]] and central nervous system (CNS) effects are seen less frequently than with morphine.<ref name="Budd">Budd K, Raffa RB. (eds.) ''Buprenorphine – The unique opioid analgesic''. Thieme, 200, {{ISBN|3-13-134211-0}}</ref> [[Central sleep apnea]] has also been reported as a side effect of long-term buprenorphine use.<ref name=opioidcase>{{cite journal | vauthors = Tchikrizov V, Richert AC, Bhardwaj SB | title = Case of buprenorphine-associated central sleep apnea resolving with dose reduction | journal = Journal of Opioid Management | volume = 18 | issue = 4 | pages = 391–394 | date = 1 July 2022 | pmid = 36052936 | doi = 10.5055/jom.2022.0732 | s2cid = 251959885 }}</ref><ref name=sleep>{{cite journal | vauthors = DeVido J, Connery H, Hill KP | title = Sleep-disordered breathing in patients with opioid use disorders in long-term maintenance on buprenorphine-naloxone: A case series | journal = Journal of Opioid Management | volume = 11 | issue = 4 | pages = 363–366 | date = 1 July 2015 | pmid = 26312963 | doi = 10.5055/jom.2015.0285 | pmc = 4754775 }}</ref>

===Respiratory effects===

The most severe side effect associated with buprenorphine is respiratory depression (insufficient breathing).<ref name=ASHP2017/> It occurs more often in those who are also taking [[benzodiazepine]]s or [[ethanol|alcohol]], or have underlying lung disease.<ref name=ASHP2017/> The usual reversal agents for opioids, such as naloxone, may be only partially effective, and additional efforts to support breathing may be required.<ref name=ASHP2017/> Respiratory depression may be less than with other opioids, particularly with chronic use.<ref name=SAM2016>{{cite web|title=Buprenorphine|url=https://www.samhsa.gov/medication-assisted-treatment/treatment/buprenorphine|website=www.samhsa.gov|access-date=3 December 2017|date=31 May 2016|archive-date=9 July 2021|archive-url=https://web.archive.org/web/20210709105557/https://www.samhsa.gov/medication-assisted-treatment/medications-counseling-related-conditions/buprenorphine|url-status=live}}</ref> In the setting of acute pain management, though, buprenorphine appears to cause the same rate of respiratory depression as other opioids such as morphine.<ref>{{cite journal | vauthors = White LD, Hodge A, Vlok R, Hurtado G, Eastern K, Melhuish TM | title = Efficacy and adverse effects of buprenorphine in acute pain management: systematic review and meta-analysis of randomised controlled trials | journal = British Journal of Anaesthesia | volume = 120 | issue = 4 | pages = 668–678 | date = April 2018 | pmid = 29576108 | doi = 10.1016/j.bja.2017.11.086 | doi-access = free }}</ref> Central sleep apnea is possible with long-term use, possibly resolving with dose reduction.<ref name=opioidcase></ref><ref name=sleep></ref>

===Buprenorphine dependence===

Buprenorphine treatment carries the risk of causing psychological or physiological (physical) dependencies. It has a slow onset of activity, with a long duration of action, and a long half-life of 24 to 60 hours. Once a patient has stabilised on the (buprenorphine) medication and programme, three options remain - continual use (buprenorphine-only medication), switching to a buprenorphine/naloxone combination, or a medically supervised withdrawal.<ref name=SAM2016/>

===Pain management===

Achieving acute opioid [[analgesia]] is difficult in persons using buprenorphine for pain management.<ref>{{cite journal | vauthors = Alford DP, Compton P, Samet JH | title = Acute pain management for patients receiving maintenance methadone or buprenorphine therapy | journal = Annals of Internal Medicine | volume = 144 | issue = 2 | pages = 127–134 | date = January 2006 | pmid = 16418412 | pmc = 1892816 | doi = 10.7326/0003-4819-144-2-200601170-00010 }}</ref> However, a systematic review found no clear benefit to bridging or stopping buprenorphine when used in opioid substitution therapy to facilitate perioperative pain management, but failure to restart it was found to pose concerns for relapse. Therefore, it is recommended that buprenophine opioid substitution therapy is continued in the perioperative period when possible. In addition preoperative pain management in patients taking buprenorphine should use an interdisciplinary approach with multimodal analgesia.<ref>Disha Mehta, Vinod Thomas, Jacinta Johnson, Brooke Scott, Sandra Cortina, Landon Berger. 2020 Continuation of Buprenorphine to Facilitate Postoperative Pain Management for Patients on Buprenorphine Opioid Agonist Therapy. 23;E163-E174. https://www.painphysicianjournal.com/current/pdf?article=NzAzMQ%3D%3D&journal=125 {{Webarchive|url=https://web.archive.org/web/20230518071739/https://www.painphysicianjournal.com/current/pdf?article=NzAzMQ%3D%3D&journal=125 |date=18 May 2023 }}</ref>

==Pharmacology==

===Pharmacodynamics===

{| class="wikitable floatright" style="font-size:small;"

|+ Buprenorphine<ref name="PDSP">{{cite web | title = PDSP K_i Database | work = Psychoactive Drug Screening Program (PDSP) | vauthors = Roth BL, Driscol J | author1-link = Bryan Roth | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 14 August 2017 | url = https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=buprenorphine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query | archive-date = 29 August 2021 | archive-url = https://web.archive.org/web/20210829111648/https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=buprenorphine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query | url-status = live }}</ref>

|-

! Site !! K_i (nM) !! Action !! Species !! Ref

|-

| {{abbrlink|MOR|μ-Opioid receptor}} || 0.7-2.3 <br />0.081 || Partial agonist || Human<br />Monkey || <ref name="pmid9686407">{{cite journal | vauthors = Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS | title = Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications | journal = NIDA Research Monograph | volume = 178 | pages = 440–466 | date = March 1998 | pmid = 9686407 }}</ref><ref name="pmid19713488">{{cite journal | vauthors = Khroyan TV, Polgar WE, Jiang F, Zaveri NT, Toll L | title = Nociceptin/orphanin FQ receptor activation attenuates antinociception induced by mixed nociceptin/orphanin FQ/mu-opioid receptor agonists | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 331 | issue = 3 | pages = 946–953 | date = December 2009 | pmid = 19713488 | pmc = 2784721 | doi = 10.1124/jpet.109.156711 }}</ref><ref name="pmid24903063">{{cite journal | vauthors = Khroyan TV, Wu J, Polgar WE, Cami-Kobeci G, Fotaki N, Husbands SM, Toll L | title = BU08073 a buprenorphine analogue with partial agonist activity at μ-receptors in vitro but long-lasting opioid antagonist activity in vivo in mice | journal = British Journal of Pharmacology | volume = 172 | issue = 2 | pages = 668–680 | date = January 2015 | pmid = 24903063 | pmc = 4292977 | doi = 10.1111/bph.12796 }}</ref><br /><ref name="pmid12409994">{{cite journal | vauthors = Negus SS, Bidlack JM, Mello NK, Furness MS, Rice KC, Brandt MR | title = Delta opioid antagonist effects of buprenorphine in rhesus monkeys | journal = Behavioural Pharmacology | volume = 13 | issue = 7 | pages = 557–570 | date = November 2002 | pmid = 12409994 | doi = 10.1097/00008877-200211000-00005 }}</ref>

|-

| {{abbrlink|DOR|δ-Opioid receptor}} || 2.9–6.1<br />0.82 || Antagonist || Human<br />Monkey || <ref name="pmid9686407" /><ref name="pmid24903063" /><ref name="pmid18997874">{{cite journal | vauthors = Lutfy K, Cowan A | title = Buprenorphine: a unique drug with complex pharmacology | journal = Current Neuropharmacology | volume = 2 | issue = 4 | pages = 395–402 | date = October 2004 | pmid = 18997874 | pmc = 2581407 | doi = 10.2174/1570159043359477 }}</ref><br /><ref name="pmid12409994" />

|-

| {{abbrlink|KOR|κ-Opioid receptor}} || 0.62–2.5<br />0.44 || Antagonist || Human<br />Monkey || <ref name="pmid9686407" /><ref name="pmid24903063" /><ref name="pmid18997874" /><br /><ref name="pmid12409994" />

|-

| {{abbrlink|NOP|Nociceptin receptor}} || 77.4 || Partial agonist || Human || <ref name="pmid19713488" /><ref name="pmid24903063" /><ref name="pmid18997874" />

|-

| [[Sigma-1 receptor|σ₁]] || >100,000 || {{abbr|ND|No data}} || {{abbr|ND|No data}} || <ref name="Freye1987">{{cite book| vauthors = Freye E |title=Opioid Agonists, Antagonists and Mixed Narcotic Analgesics|chapter=Interaction of Mixed Agonist-Antagonists with Different Receptor Sites Using Nalbuphine as a Model Substance|year=1987|pages=67–78|doi=10.1007/978-3-642-71854-0_6|isbn=978-3-540-17471-4}}</ref>

|-

| [[Sigma-2 receptor|σ₂]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}

|-

| {{abbrlink|NMDA|N-Methyl-D-aspartate receptor}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}

|-

| {{abbrlink|TLR4|Toll-like receptor 4}} || >10,000 || Agonist || Human || <ref name="pmid19679181">{{cite journal | vauthors = Hutchinson MR, Zhang Y, Shridhar M, Evans JH, Buchanan MM, Zhao TX, Slivka PF, Coats BD, Rezvani N, Wieseler J, Hughes TS, Landgraf KE, Chan S, Fong S, Phipps S, Falke JJ, Leinwand LA, Maier SF, Yin H, Rice KC, Watkins LR | title = Evidence that opioids may have toll-like receptor 4 and MD-2 effects | journal = Brain, Behavior, and Immunity | volume = 24 | issue = 1 | pages = 83–95 | date = January 2010 | pmid = 19679181 | pmc = 2788078 | doi = 10.1016/j.bbi.2009.08.004 }}</ref>

|-

| {{abbrlink|SERT|Serotonin transporter}} || >100,000 || {{abbr|ND|No data}} || Rat || <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 = 1263–1270 | date = September 1995 | pmid = 7562497 }}</ref>

|-

| {{abbrlink|NET|Norepinephrine transporter}} || >100,000 || {{abbr|ND|No data}} || Rat || <ref name="pmid7562497" />

|-

| {{abbrlink|DAT|Dopamine transporter}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}

|-

| {{abbrlink|VGSC|Voltage-gated sodium channel}} || 33,000 ([[IC50|IC₅₀]]) || Inhibitor || Rodent || <ref name="pmid22504149">{{cite journal | vauthors = Leffler A, Frank G, Kistner K, Niedermirtl F, Koppert W, Reeh PW, Nau C | title = Local anesthetic-like inhibition of voltage-gated Na(+) channels by the partial μ-opioid receptor agonist buprenorphine | journal = Anesthesiology | volume = 116 | issue = 6 | pages = 1335–1346 | date = June 2012 | pmid = 22504149 | doi = 10.1097/ALN.0b013e3182557917 | doi-access = free }}</ref>

|-

|- class="sortbottom"

| colspan="5" | Values are K_i (nM), unless otherwise noted. The smaller<br />the value, the more strongly the drug binds to the site.

|}

====Opioid receptor modulator====

Buprenorphine has been reported to possess these following [[pharmacological activity|pharmacological activities]]:<ref name="pmid24903063" />

* [[μ-Opioid receptor]] (MOR): Very high affinity [[partial agonist]]:<ref name="Gudin_2020">{{cite journal | vauthors = Gudin J, Fudin J | title = A Narrative Pharmacological Review of Buprenorphine: A Unique Opioid for the Treatment of Chronic Pain | journal = Pain and Therapy | volume = 9 | issue = 1 | pages = 41–54 | date = June 2020 | pmid = 31994020 | pmc = 7203271 | doi = 10.1007/s40122-019-00143-6 }}</ref> at low doses, the MOR-mediated effects of buprenorphine are comparable to those of other narcotics, but these effects reach a "ceiling" as the receptor population is saturated.<ref name="pmid18997874" /> This behavior is responsible for several unique properties: buprenorphine greatly reduces the effect of most other MOR agonists,<ref name="pmid12481193" /> can cause precipitated withdrawal when used in actively opioid dependent persons,<ref name="pmid12481193" /> and has a lower incidence of respiratory depression and fatal overdose relative to full MOR agonists.<ref>{{cite journal | vauthors = Khanna IK, Pillarisetti S | title = Buprenorphine - an attractive opioid with underutilized potential in treatment of chronic pain | journal = Journal of Pain Research | volume = 8 | pages = 859–870 | date = 2015 | pmid = 26672499 | pmc = 4675640 | doi = 10.2147/JPR.S85951 | doi-access = free }}</ref>

* [[κ-Opioid receptor]] (KOR): High affinity antagonist<ref name="Gudin_2020" />—this activity is hypothesized to underlie some of the effects of buprenorphine on mood disorders and addiction.<ref>{{cite journal | vauthors = Madison CA, Eitan S | title = Buprenorphine: prospective novel therapy for depression and PTSD | journal = Psychological Medicine | volume = 50 | issue = 6 | pages = 881–893 | date = April 2020 | pmid = 32204739 | doi = 10.1017/S0033291720000525 | s2cid = 214630021 }}</ref><ref>{{cite journal | vauthors = Stefanowski B, Antosik-Wójcińska A, Święcicki Ł | title = The use of buprenorphine in the treatment of drug-resistant depression - an overview of the studies | journal = Psychiatria Polska | volume = 54 | issue = 2 | pages = 199–207 | date = April 2020 | pmid = 32772054 | doi = 10.12740/PP/102658 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Carlezon WA, Béguin C, Knoll AT, Cohen BM | title = Kappa-opioid ligands in the study and treatment of mood disorders | journal = Pharmacology & Therapeutics | volume = 123 | issue = 3 | pages = 334–343 | date = September 2009 | pmid = 19497337 | pmc = 2740476 | doi = 10.1016/j.pharmthera.2009.05.008 }}</ref>

* [[δ-Opioid receptor]] (DOR): High affinity antagonist<ref name="Gudin_2020" /><ref name="Ben2017">{{cite book|vauthors=Benzon H, Raja S, Fishman S, Liu SS, Cohen SP|url=https://books.google.com/books?id=w3g4DwAAQBAJ&pg=PA382|title=Essentials of Pain Medicine E-Book|date=2017|publisher=Elsevier Health Sciences|isbn=9780323445412|page=382|access-date=29 May 2020|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114153757/https://books.google.com/books?id=w3g4DwAAQBAJ&pg=PA382|url-status=live}}</ref>

* [[Nociceptin receptor]] (NOP, ORL-1): Weak affinity, very weak partial agonist<ref name="Gudin_2020" />

In simplified terms, buprenorphine can essentially be thought of as a nonselective, mixed [[agonist–antagonist]] [[opioid receptor modulator]],<ref name="pmid572694">{{cite journal | vauthors = Jacob JJ, Michaud GM, Tremblay EC | title = Mixed agonist-antagonist opiates and physical dependence | journal = British Journal of Clinical Pharmacology | volume = 7 | issue = Suppl 3 | pages = 291S–296S | year = 1979 | pmid = 572694 | pmc = 1429306 | doi = 10.1111/j.1365-2125.1979.tb04703.x }}</ref> acting as an unusually high affinity, weak [[partial agonist]] of the MOR, a high affinity [[receptor antagonist|antagonist]] of the KOR and DOR, and a relatively low affinity, very weak partial agonist of the ORL-1/NOP.<ref name="pmid18997874" /><ref name="pmid18567516">{{cite journal | vauthors = Kress HG | title = Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine | journal = European Journal of Pain | volume = 13 | issue = 3 | pages = 219–230 | date = March 2009 | pmid = 18567516 | doi = 10.1016/j.ejpain.2008.04.011 | s2cid = 8243410 }}</ref><ref name="pmid12481193">{{cite journal | vauthors = Robinson SE | title = Buprenorphine: an analgesic with an expanding role in the treatment of opioid addiction | journal = CNS Drug Reviews | volume = 8 | issue = 4 | pages = 377–390 | year = 2002 | pmid = 12481193 | pmc = 6741692 | doi = 10.1111/j.1527-3458.2002.tb00235.x }}</ref><ref name="RuizStrain2011">{{cite book | vauthors = Ruiz P, Strain EC | title = Lowinson and Ruiz's Substance Abuse: A Comprehensive Textbook | url = https://books.google.com/books?id=w4ZUJAdleTsC&pg=PA439 | year = 2011 | publisher = Lippincott Williams & Wilkins | isbn = 978-1-60547-277-5 | page = 439 | access-date = 14 March 2016 | archive-date = 14 January 2023 | archive-url = https://web.archive.org/web/20230114153759/https://books.google.com/books?id=w4ZUJAdleTsC&pg=PA439 | url-status = live }}</ref><ref name="pmid24484983">{{cite book | vauthors = Bidlack JM | title = Mixed κ/μ partial opioid agonists as potential treatments for cocaine dependence | chapter = Mixed Kappa/Mu Partial Opioid Agonists as Potential Treatments for Cocaine Dependence | series = Advances in Pharmacology | volume = 69 | pages = 387–418 | date = 2014 | pmid = 24484983 | doi = 10.1016/B978-0-12-420118-7.00010-X | isbn = 9780124201187 }}</ref><ref name="EhrichTurncliff2014">{{cite journal | vauthors = Ehrich E, Turncliff R, Du Y, Leigh-Pemberton R, Fernandez E, Jones R, Fava M | title = Evaluation of opioid modulation in major depressive disorder | journal = Neuropsychopharmacology | volume = 40 | issue = 6 | pages = 1448–1455 | date = May 2015 | pmid = 25518754 | pmc = 4397403 | doi = 10.1038/npp.2014.330 }}</ref>

Although buprenorphine is a partial agonist of the MOR, human studies have found that it acts like a full agonist with respect to analgesia in opioid-intolerant individuals.<ref name="pmid18958460">{{cite journal | vauthors = Coller JK, Christrup LL, Somogyi AA | title = Role of active metabolites in the use of opioids | journal = European Journal of Clinical Pharmacology | volume = 65 | issue = 2 | pages = 121–139 | date = February 2009 | pmid = 18958460 | doi = 10.1007/s00228-008-0570-y | s2cid = 9977741 }}</ref> Conversely, buprenorphine behaves like a partial agonist of the MOR with respect to [[respiratory depression]].<ref name="pmid18958460" />

Buprenorphine is also known to bind to with high affinity and antagonize the putative [[ε-opioid receptor]].<ref name="pmid12435410">{{cite journal | vauthors = Mizoguchi H, Wu HE, Narita M, Hall FS, Sora I, Uhl GR, Nagase H, Tseng LF | title = Antagonistic property of buprenorphine for putative epsilon-opioid receptor-mediated G-protein activation by beta-endorphin in pons/medulla of the mu-opioid receptor knockout mouse | journal = Neuroscience | volume = 115 | issue = 3 | pages = 715–721 | year = 2002 | pmid = 12435410 | doi = 10.1016/s0306-4522(02)00486-4 | s2cid = 54316989 }}</ref><ref name="pmid12721333">{{cite journal | vauthors = Mizoguchi H, Spaulding A, Leitermann R, Wu HE, Nagase H, Tseng LF | title = Buprenorphine blocks epsilon- and micro-opioid receptor-mediated antinociception in the mouse | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 306 | issue = 1 | pages = 394–400 | date = July 2003 | pmid = 12721333 | doi = 10.1124/jpet.103.048835 | s2cid = 44036890 }}</ref>

Full analgesic efficacy of buprenorphine requires both [[exon]] 11-<ref name="pmid19077058">{{cite journal | vauthors = Xu J, Xu M, Hurd YL, Pasternak GW, Pan YX | title = Isolation and characterization of new exon 11-associated N-terminal splice variants of the human mu opioid receptor gene | journal = Journal of Neurochemistry | volume = 108 | issue = 4 | pages = 962–972 | date = February 2009 | pmid = 19077058 | pmc = 2727151 | doi = 10.1111/j.1471-4159.2008.05833.x }}</ref> and exon 1-associated [[mu-opioid receptor|μ-opioid receptor]] [[splice variant]]s.<ref>Grinnell S et al. (2014): Buprenorphine analgesia requires exon 11-associated mu opioid receptor splice variants. ''The FASEB Journal''</ref>

The [[active metabolite]]s of buprenorphine are not thought to be clinically important in its CNS effects.<ref name="pmid18958460"/>

In [[positron emission tomography]] (PET) [[medical imaging|imaging]] studies, buprenorphine was found to decrease whole-brain MOR availability due to receptor occupancy by 41% (i.e., 59% availability) at 2&nbsp;mg, 80% (i.e., 20% availability) at 16&nbsp;mg, and 84% (i.e., 16% availability) at 32&nbsp;mg.<ref name="ColasantiLingford-HughesNutt2013">{{cite book | veditors = Miller PM | title = Biological Research on Addiction | series = Comprehensive Addictive Behaviors and Disorders | volume = 2 | vauthors = Colasanti A, Lingford-Hughes A, Nutt D | chapter = Opioids Neuroimaging | date = 2013 | pages = 675–687 | publisher = Elsevier | doi = 10.1016/B978-0-12-398335-0.00066-2 | isbn = 9780123983350 | url = }}</ref><ref name="pmid10942856">{{cite journal | vauthors = Zubieta J, Greenwald MK, Lombardi U, Woods JH, Kilbourn MR, Jewett DM, Koeppe RA, Schuster CR, Johanson CE | title = Buprenorphine-induced changes in mu-opioid receptor availability in male heroin-dependent volunteers: a preliminary study | journal = Neuropsychopharmacology | volume = 23 | issue = 3 | pages = 326–334 | date = September 2000 | pmid = 10942856 | doi = 10.1016/S0893-133X(00)00110-X | s2cid = 27350905 | doi-access = free }}</ref><ref name="pmid12902992">{{cite journal | vauthors = Greenwald MK, Johanson CE, Moody DE, Woods JH, Kilbourn MR, Koeppe RA, Schuster CR, Zubieta JK | title = Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers | journal = Neuropsychopharmacology | volume = 28 | issue = 11 | pages = 2000–2009 | date = November 2003 | pmid = 12902992 | doi = 10.1038/sj.npp.1300251 | s2cid = 20773085 | doi-access = free }}</ref><ref name="pmid16950210">{{cite journal | vauthors = Greenwald M, Johanson CE, Bueller J, Chang Y, Moody DE, Kilbourn M, Koeppe R, Zubieta JK | title = Buprenorphine duration of action: mu-opioid receptor availability and pharmacokinetic and behavioral indices | journal = Biological Psychiatry | volume = 61 | issue = 1 | pages = 101–110 | date = January 2007 | pmid = 16950210 | doi = 10.1016/j.biopsych.2006.04.043 | s2cid = 46105421 }}</ref>

====Other actions====

Unlike some other opioids and opioid antagonists, buprenorphine binds only weakly to and possesses little if any activity at the [[sigma receptor]].<ref name="Doweiko2014">{{cite book| vauthors = Doweiko HE |title=Concepts of Chemical Dependency|url=https://books.google.com/books?id=IuAbCgAAQBAJ&pg=PA149|date=14 March 2014|publisher=Cengage Learning|isbn=978-1-285-45717-8|pages=149–}}</ref><ref>{{cite book|title=USP DI.|year = 1997|url=https://books.google.com/books?id=I-SwfGseCqoC|publisher=United States Pharmacopeial Convention|isbn = 9780913595947}}</ref>

Buprenorphine also blocks [[voltage-gated sodium channel]]s via the [[local anesthetic]] binding site, and this underlies its potent local anesthetic properties.<ref name="pmid22504149" />

Similarly to various other opioids, buprenorphine has also been found to act as an agonist of the [[toll-like receptor 4]], albeit with very low affinity.<ref name="pmid19679181" />

===Pharmacokinetics===

Buprenorphine is [[metabolism|metabolized]] by the [[liver]], via [[CYP3A4]] (also [[CYP2C8]] seems to be involved) [[isozyme]]s of the [[cytochrome P450 oxidase|cytochrome P450]] [[enzyme]] system, into [[norbuprenorphine]] (by ''N''-dealkylation). The [[glucuronidation]] of buprenorphine is primarily carried out by [[UGT1A1]] and [[UGT2B7]], and that of norbuprenorphine by [[UGT1A1]] and [[UGT1A3]]. These glucuronides are then [[elimination (pharmacology)|eliminated]] mainly through [[excretion]] into [[bile]]. The [[elimination half-life]] of buprenorphine is 20 to 73 hours (mean 37 hours). Due to the mainly hepatic elimination, no risk of accumulation exists in people with [[renal impairment]].<ref>{{cite journal | vauthors = Moody DE, Fang WB, Lin SN, Weyant DM, Strom SC, Omiecinski CJ | title = Effect of rifampin and nelfinavir on the metabolism of methadone and buprenorphine in primary cultures of human hepatocytes | journal = Drug Metabolism and Disposition | volume = 37 | issue = 12 | pages = 2323–2329 | date = December 2009 | pmid = 19773542 | pmc = 2784702 | doi = 10.1124/dmd.109.028605 }}</ref>

One of the major [[active metabolite]]s of buprenorphine is norbuprenorphine, which, in contrast to buprenorphine itself, is a [[full agonist]] of the MOR, DOR, and ORL-1, and a partial agonist at the KOR.<ref name="pmid">{{cite journal | vauthors = Yassen A, Kan J, Olofsen E, Suidgeest E, Dahan A, Danhof M | title = Pharmacokinetic-pharmacodynamic modeling of the respiratory depressant effect of norbuprenorphine in rats | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 321 | issue = 2 | pages = 598–607 | date = May 2007 | pmid = 17283225 | doi = 10.1124/jpet.106.115972 | s2cid = 11921738 }}</ref><ref name="pmid11303059">{{cite journal | vauthors = Huang P, Kehner GB, Cowan A, Liu-Chen LY | title = Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 297 | issue = 2 | pages = 688–695 | date = May 2001 | pmid = 11303059 }}</ref> However, relative to buprenorphine, norbuprenorphine has extremely little antinociceptive potency (1/50th that of buprenorphine), but markedly depresses respiration (10-fold more than buprenorphine).<ref name="pmid22739506">{{cite journal | vauthors = Brown SM, Campbell SD, Crafford A, Regina KJ, Holtzman MJ, Kharasch ED | title = P-glycoprotein is a major determinant of norbuprenorphine brain exposure and antinociception | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 343 | issue = 1 | pages = 53–61 | date = October 2012 | pmid = 22739506 | pmc = 3464040 | doi = 10.1124/jpet.112.193433 }}</ref> This may be explained by very poor brain penetration of norbuprenorphine due to a high affinity of the compound for [[P-glycoprotein]].<ref name="pmid22739506" /> In contrast to norbuprenorphine, buprenorphine and its [[glucuronide]] metabolites are negligibly transported by P-glycoprotein.<ref name="pmid22739506" />

The glucuronides of buprenorphine and norbuprenorphine are also [[biological activity|biologically active]], and represent major active metabolites of buprenorphine.<ref name="pmid22037640">{{cite journal | vauthors = Brown SM, Holtzman M, Kim T, Kharasch ED | title = Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active | journal = Anesthesiology | volume = 115 | issue = 6 | pages = 1251–1260 | date = December 2011 | pmid = 22037640 | pmc = 3560935 | doi = 10.1097/ALN.0b013e318238fea0 }}</ref> [[Buprenorphine-3-glucuronide]] has affinity for the MOR (K_i = 4.9 pM), DOR (K_i = 270 nM) and ORL-1 (K_i = 36 μM), and no affinity for the KOR. It has a small antinociceptive effect and no effect on respiration. [[Norbuprenorphine-3-glucuronide]] has no affinity for the MOR or DOR, but does bind to the KOR (K_i = 300 nM) and ORL-1 (K_i = 18 μM). It has a sedative effect but no effect on respiration.

==Chemistry==

Buprenorphine is a semisynthetic derivative of [[thebaine]],<ref>{{cite journal | vauthors = Heel RC, Brogden RN, Speight TM, Avery GS | title = Buprenorphine: a review of its pharmacological properties and therapeutic efficacy | journal = Drugs | volume = 17 | issue = 2 | pages = 81–110 | date = February 1979 | pmid = 378645 | doi = 10.2165/00003495-197917020-00001 | s2cid = 19577410 }}</ref> and is fairly soluble in water, as its [[hydrochloride]] salt.<ref name = MD/> It degrades in the presence of light.<ref name = MD/>

===Detection in body fluids===

Buprenorphine and norbuprenorphine may be quantified in blood or urine to monitor use or non-medical recreational use, confirm a diagnosis of poisoning, or assist in a medicolegal investigation. A significant overlap of drug concentrations exists in body fluids within the possible spectrum of physiological reactions ranging from asymptomatic to comatose. Therefore, having knowledge of both the route of administration of the drug and the level of tolerance to opioids of the individual is critical when results are interpreted.<ref>{{cite book | vauthors = Baselt R | date = 2008 | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | pages = 190–192 | isbn = 978-0962652370}}</ref>

==History==

In 1969, researchers at Reckitt and Colman (now [[Reckitt Benckiser]]) had spent 10 years attempting to synthesize an opioid compound "with structures substantially more complex than morphine [that] could retain the desirable actions whilst shedding the undesirable side effects". [[Physical dependence]] and withdrawal from buprenorphine itself remain important issues, since buprenorphine is a long-acting opioid.<ref>{{cite web|title=IMPORTANT SAFETY INFORMATION|url=http://www.suboxone.com/medical-treatment/side-effects-adverse-events|access-date=25 June 2016|archive-url=https://web.archive.org/web/20190318223620/https://www.suboxone.com/medical-treatment/side-effects-adverse-events|archive-date=18 March 2019|url-status=dead}}</ref> Reckitt found success when researchers synthesized RX6029 which had showed success in reducing dependence in test animals. RX6029 was named buprenorphine and began trials on humans in 1971.<ref>{{cite journal | vauthors = Campbell ND, Lovell AM | title = The history of the development of buprenorphine as an addiction therapeutic | journal = Annals of the New York Academy of Sciences | volume = 1248 | issue = 1 | pages = 124–139 | date = February 2012 | pmid = 22256949 | doi = 10.1111/j.1749-6632.2011.06352.x | s2cid = 28395410 | bibcode = 2012NYASA1248..124C }}</ref><ref name="In Pursuit of the Holy Grail">{{cite book |url=http://rzbl04.biblio.etc.tu-bs.de:8080/docportal/servlets/MCRFileNodeServlet/DocPortal_derivate_00001868/NIDA179.pdf |title=Problems of Drug Dependence, 1998: Proceedings of the 66th Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc. |editor=Louis S. Harris |publisher=NIDA Research Monograph 179 |year=1998 |access-date=5 August 2012 |archive-url=https://web.archive.org/web/20161203055853/http://rzbl04.biblio.etc.tu-bs.de:8080/docportal/servlets/MCRFileNodeServlet/DocPortal_derivate_00001868/NIDA179.pdf |archive-date=3 December 2016 |url-status=dead }}</ref> By 1978, buprenorphine was first launched in the UK as an injection to treat severe pain, with a sublingual formulation released in 1982.

==Society and culture==

===Regulation===

====United States====

In the United States, buprenorphine and buprenorphine with naloxone were approved for opioid use disorder by the [[Food and Drug Administration]] in October 2002.<ref name=FDAApproval>{{cite letter | vauthors = McCormick CG | url = http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2002/20732,20733ltr.pdf | recipient = Reckitt Benckiser | subject = Subutex and Suboxone Approval Letter]. | publisher = U.S. Food and Drug Administration | date = 8 October 2002 }}</ref> The DEA rescheduled buprenorphine from a [[Controlled Substances Act|schedule V drug]] to a [[Controlled Substances Act|schedule III drug]] just before approval.<ref>{{Federal Register|67|62354}}, 7 October 2002</ref> The ACSCN for buprenorphine is 9064, and being a schedule III substance, it does not have an annual manufacturing quota imposed by the DEA.<ref>{{cite web | url = http://www.deadiversion.usdoj.gov/quotas/conv_factor/index.html | title = Quotas – Conversion Factors for Controlled Substances | work = Deadiversion.usdoj.gov | access-date = 7 November 2016 | archive-date = 2 March 2016 | archive-url = https://web.archive.org/web/20160302162948/http://deadiversion.usdoj.gov/quotas/conv_factor/index.html | url-status = dead }}</ref> The salt in use is the hydrochloride, which has a free-base conversion ratio of 0.928.

In the years before buprenorphine/naloxone was approved, Reckitt Benckiser had lobbied Congress to help craft the [[Drug Addiction Treatment Act]] of 2000, which gave authority to the Secretary of Health and Human Services to grant a waiver to physicians with certain training to prescribe and administer schedule III, IV, or V narcotic drugs for the treatment of addiction or detoxification. Before this law was passed, such treatment was permitted only in clinics designed specifically for drug addiction.<ref name=SAMHSA>{{cite web | url = http://buprenorphine.samhsa.gov/titlexxxv.html | title = Drug Addiction Treatment Act of 2000 | archive-url = https://web.archive.org/web/20130304203025/http://buprenorphine.samhsa.gov/titlexxxv.html | archive-date=4 March 2013 | work = SAMHSA, U.S. Department of Health & Human Services }}</ref>

The waiver, which can be granted after the completion of an eight-hour course, was required for outpatient treatment of opioid addiction with buprenorphine from 2000 to 2021. Initially, the number of people each approved physician could treat was limited to 10. This was eventually modified to allow approved physicians to treat up to 100 people with buprenorphine for opioid addiction in an outpatient setting.<ref>{{cite web | url = http://naabt.org/30_patient_limit.cfm/ | title = The National Alliance of Advocates for Buprenorphine Treatment | work = naabt.org | access-date = 19 May 2013 | archive-date = 12 November 2020 | archive-url = https://web.archive.org/web/20201112022606/http://www.naabt.org/30_patient_limit.cfm | url-status = live }}</ref> This limit was increased by the Obama administration, raising the number of patients to which doctors can prescribe to 275.<ref>{{cite web | url = http://www.businessinsider.com/obama-buprenorphine-suboxone-policy-2016-7 | title = Obama administration's change on buprenorphine policy | work = Business Insider | date = 6 July 2016 | access-date = 7 November 2016 | archive-date = 18 March 2020 | archive-url = https://web.archive.org/web/20200318181953/https://www.businessinsider.com/obama-buprenorphine-suboxone-policy-2016-7 | url-status = live }}</ref> On 14 January 2021, the US Department of Health and Human Services announced that the waiver would no longer be required to prescribe buprenorphine to treat up to 30 people concurrently.<ref>{{cite press release | url = https://www.hhs.gov/about/news/2021/01/14/hhs-expands-access-to-treatment-for-opioid-use-disorder.html | title = HHS Expands Access to Treatment for Opioid Use Disorder | work = US Deptartment of Health and Human Services | date = 14 January 2021 | access-date = 14 January 2021 | archive-date = 14 January 2021 | archive-url = https://web.archive.org/web/20210114212923/https://www.hhs.gov/about/news/2021/01/14/hhs-expands-access-to-treatment-for-opioid-use-disorder.html | url-status = dead }}</ref>

New Jersey authorized paramedics to give buprenorphine to people at the scene after they have recovered from an overdose.<ref>{{cite web|url=https://www.statnews.com/2019/06/26/new-jersey-paramedics-buprenorphine/|title=In national first, N.J. program will let paramedics administer buprenorphine|date=26 June 2019|website=STAT|access-date=21 November 2019|archive-date=3 October 2019|archive-url=https://web.archive.org/web/20191003145623/https://www.statnews.com/2019/06/26/new-jersey-paramedics-buprenorphine/|url-status=live}}</ref>

====Europe====

In the European Union, Subutex and Suboxone, buprenorphine's high-dose sublingual tablet preparations, were approved for opioid use disorder treatment in September 2006.<ref>{{cite web | url = http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000697/human_med_001067.jsp&mid=WC0b01ac058001d124 | title = Suboxone EU Approval | work = Ema.europa.eu | access-date = 7 November 2016 | archive-date = 24 December 2016 | archive-url = https://web.archive.org/web/20161224231647/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F000697%2Fhuman_med_001067.jsp&mid=WC0b01ac058001d124 | url-status = live }}</ref> In the [[Netherlands]], buprenorphine is a list II drug of the [[Opium Law]], though special rules and guidelines apply to its prescription and dispensation. In France, where buprenorphine prescription by general practitioners and dispensed by pharmacies has been permitted since the mid-1990s as a response to HIV and overdose risk. Deaths caused by heroin overdose were reduced by four-fifths between 1994 and 2002, and incidence of AIDS among people who inject drugs in France fell from 25% in the mid-1990s to 6% in 2010.<ref>{{cite journal | vauthors = Poloméni P, Schwan R | title = Management of opioid addiction with buprenorphine: French history and current management | journal = International Journal of General Medicine | volume = 7 | pages = 143–148 | date = 3 March 2014 | pmid = 24623988 | pmc = 3949694 | doi = 10.2147/IJGM.S53170 | doi-access = free }}</ref>

===Brand names===

Buprenorphine is available under the trade names Cizdol, Brixadi (approved in the US by FDA for addiction treatment in 2023), Suboxone (with naloxone), Subutex (typically used for opioid use disorder), Zubsolv, Bunavail, Buvidal (approved in the UK, Europe and Australia for addiction treatment in 2018), Sublocade (approved in the US in 2018),<ref>{{cite press release|url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-once-monthly-buprenorphine-injection-medication-assisted-treatment-option-opioid |title=FDA approves first once-monthly buprenorphine injection, a medication-assisted treatment option for opioid use disorder|website=U.S. Food and Drug Administration|date=30 November 2017|access-date=5 December 2017|archive-date=3 December 2017|archive-url=https://web.archive.org/web/20171203063547/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm587312.htm|url-status=live}}</ref><ref>{{cite news|url=https://www.reuters.com/article/us-indivior-opioids/indivior-drug-to-fight-opioid-addiction-approved-by-u-s-fda-idUSKBN1DV47M|title=Indivior drug to fight opioid addiction approved by U.S. FDA|date=2017|work=Reuters|access-date=5 December 2017|archive-date=5 December 2017|archive-url=https://web.archive.org/web/20171205093202/https://www.reuters.com/article/us-indivior-opioids/indivior-drug-to-fight-opioid-addiction-approved-by-u-s-fda-idUSKBN1DV47M|url-status=live}}</ref><ref>{{cite web|url=https://www.empr.com/home/news/sublocade-now-available-for-moderate-to-severe-opioid-use-disorder/|title=Sublocade Now Available for Moderate-to-Severe Opioid Use Disorder|date=1 March 2018|website=MPR|access-date=23 September 2019|archive-date=23 September 2019|archive-url=https://web.archive.org/web/20190923021822/https://www.empr.com/home/news/sublocade-now-available-for-moderate-to-severe-opioid-use-disorder/|url-status=live}}</ref> Probuphine, Temgesic ([[sublingual]] tablets for moderate to severe pain), Buprenex (solutions for injection often used for acute pain in primary-care settings), Norspan, and Butrans ([[transdermal patch|transdermal preparations]] used for chronic pain).<ref name = MD>{{cite web|title=Buprenorphine|work=Martindale: The Complete Drug Reference|publisher=Pharmaceutical Press|location=London, UK|date=14 January 2014|access-date=6 April 2014|url=http://www.medicinescomplete.com/mc/martindale/current/ms-19995-d.htm|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828013027/https://about.medicinescomplete.com/wp-content/themes/mc-marketing/assets/images/favicons-tiles/favicon.ico|url-status=live}}</ref> In Poland buprenorphine is available under the trade names Bunondol (for pain treatment, when morphine is too little; amounts of 0.2mg and 0.4mg) and Bunorfin (for addicts substitution in amount of 2 and 8mg).

==Research==

===Microdosing===

There is some evidence that a buprenorphine [[microdosing]] regime, started before [[opioid withdrawal]] symptoms have started, can be effective in helping people transitioning away from opioid dependence.<ref>{{cite journal |vauthors=Ahmed S, Bhivandkar S, Lonergan BB, Suzuki J |title=Microinduction of Buprenorphine/Naloxone: A Review of the Literature |journal=Am J Addict |volume=30 |issue=4 |pages=305–315 |date=July 2021 |pmid=33378137 |doi=10.1111/ajad.13135 |s2cid=229721826 |type=Review}}</ref>

===Depression===

Some evidence supports the use of buprenorphine for depression.<ref>{{cite journal | vauthors = Stanciu CN, Glass OM, Penders TM | title = Use of Buprenorphine in treatment of refractory depression-A review of current literature | journal = Asian Journal of Psychiatry | volume = 26 | pages = 94–98 | date = April 2017 | pmid = 28483102 | doi = 10.1016/j.ajp.2017.01.015 }}</ref> [[Buprenorphine/samidorphan]], a [[combination drug|combination product]] of buprenorphine and [[samidorphan]] (a preferential [[mu-opioid receptor|μ-opioid receptor]] [[receptor antagonist|antagonist]]), appears useful for [[treatment-resistant depression]].<ref>{{cite journal | vauthors = Ragguett RM, Rong C, Rosenblat JD, Ho RC, McIntyre RS | title = Pharmacodynamic and pharmacokinetic evaluation of buprenorphine + samidorphan for the treatment of major depressive disorder | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 14 | issue = 4 | pages = 475–482 | date = April 2018 | pmid = 29621905 | doi = 10.1080/17425255.2018.1459564 | s2cid = 4633923 }}</ref>

===Cocaine dependence===

In combination with [[samidorphan]] or naltrexone (μ-opioid receptor antagonists), buprenorphine is under investigation for the treatment of [[cocaine dependence]], and recently demonstrated effectiveness for this indication in a large-scale (n = 302) [[clinical trial]] (at a high buprenorphine dose of 16&nbsp;mg, but not a low dose of 4&nbsp;mg).<ref name="LingHillhouse2016">{{cite journal | vauthors = Ling W, Hillhouse MP, Saxon AJ, Mooney LJ, Thomas CM, Ang A, Matthews AG, Hasson A, Annon J, Sparenborg S, Liu DS, McCormack J, Church S, Swafford W, Drexler K, Schuman C, Ross S, Wiest K, Korthuis PT, Lawson W, Brigham GS, Knox PC, Dawes M, Rotrosen J | title = Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study | journal = Addiction | volume = 111 | issue = 8 | pages = 1416–1427 | date = August 2016 | pmid = 26948856 | pmc = 4940267 | doi = 10.1111/add.13375 }}</ref><ref name="Reuters2012">{{cite web | url = https://www.reuters.com/article/2012/05/29/idUS197896+29-May-2012+BW20120529 | work = Reuters | title = Alkermes Presents Positive Clinical Data of ALKS 5461 at 52nd Annual New Clinical Drug Evaluation Unit Meeting | year = 2012 | access-date = 30 June 2017 | archive-date = 24 September 2015 | archive-url = https://web.archive.org/web/20150924164224/http://www.reuters.com/article/2012/05/29/idUS197896+29-May-2012+BW20120529 | url-status = dead }}</ref>

===Neonatal abstinence===

Buprenorphine has been used in the treatment of the [[neonatal abstinence syndrome]],<ref>{{cite journal | vauthors = Kraft WK, Gibson E, Dysart K, Damle VS, Larusso JL, Greenspan JS, Moody DE, Kaltenbach K, Ehrlich ME | title = Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial | journal = Pediatrics | volume = 122 | issue = 3 | pages = e601–e607 | date = September 2008 | pmid = 18694901 | pmc = 2574639 | doi = 10.1542/peds.2008-0571 }}</ref> a condition in which newborns exposed to opioids during pregnancy demonstrate signs of withdrawal.<ref>{{cite journal | vauthors = Kraft WK, van den Anker JN | title = Pharmacologic management of the opioid neonatal abstinence syndrome | journal = Pediatric Clinics of North America | volume = 59 | issue = 5 | pages = 1147–1165 | date = October 2012 | pmid = 23036249 | pmc = 4709246 | doi = 10.1016/j.pcl.2012.07.006 }}</ref> In the United States, use currently is limited to infants enrolled in a clinical trial conducted under an FDA-approved investigational new drug (IND) application.<ref>{{ClinicalTrialsGov|NCT00521248|Buprenorphine for the Treatment of Neonatal Abstinence Syndrome}}</ref> Preliminary research suggests that buprenorphine is associated with shorter time in hospital for neonates, compared to methadone.<ref>{{cite journal | vauthors = Tran TH, Griffin BL, Stone RH, Vest KM, Todd TJ | title = Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women | journal = Pharmacotherapy | volume = 37 | issue = 7 | pages = 824–839 | date = July 2017 | pmid = 28543191 | doi = 10.1002/phar.1958 | quote = Currently, methadone and buprenorphine are both widely used as the backbone of MAT [medication-assisted treatment]. The distinguishing outcomes in studies among these two opioid agonists are that infants exposed to buprenorphine in clinical trials required shorter treatment duration, less medication to treat the NAS symptoms and experienced shorter hospitalizations compared to infants exposed to methadone. A caveat to these findings is that some of the supporting data were based on using buprenorphine in combination with naloxone instead of buprenorphine as a single agent. | s2cid = 13772333 }}</ref> An ethanolic formulation used in neonates is stable at room temperature for at least 30 days.<ref>{{cite journal | vauthors = Anagnostis EA, Sadaka RE, Sailor LA, Moody DE, Dysart KC, Kraft WK | title = Formulation of buprenorphine for sublingual use in neonates | journal = The Journal of Pediatric Pharmacology and Therapeutics | volume = 16 | issue = 4 | pages = 281–284 | date = October 2011 | pmid = 22768012 | pmc = 3385042 | doi = 10.5863/1551-6776-16.4.281 }}</ref>

== Veterinary uses ==

Veterinarians administer buprenorphine for [[perioperative]] pain, particularly in cats, where its effects are similar to morphine. The drug's legal status and lower potential for human abuse makes it an attractive alternative to other opioids.<ref>{{cite web |vauthors=Martinez M |title=Options in perioperative analgesia: buprenorphine v. methadone |url=https://www.veterinary-practice.com/article/options-in-perioperative-analgesia-buprenorphine-v-methadone |website=Veterinary Practice |date=May 2014 |access-date=19 January 2022 |archive-date=19 January 2022 |archive-url=https://web.archive.org/web/20220119231147/https://www.veterinary-practice.com/article/options-in-perioperative-analgesia-buprenorphine-v-methadone |url-status=live }}</ref>

It has veterinary medical use for treatment of pain in dogs and cats, as well as other animals.<ref name="Claude">{{cite web |url=http://www.cliniciansbrief.com/sites/default/files/attachments/MEDS_Bupreorphine.pdf |title=Buprenorphine | vauthors = Claude A |date=June 2015 |publisher=cliniciansbrief.com |access-date=25 February 2017 |archive-url=https://web.archive.org/web/20170516195037/http://www.cliniciansbrief.com/sites/default/files/attachments/MEDS_Bupreorphine.pdf |archive-date=16 May 2017 |url-status=dead }}</ref><ref name="Riviere & Papich">{{cite book |vauthors=Kukanich B, Papich MG |veditors=Riviere JE, Papich MG |title=Veterinary Pharmacology and Therapeutics |chapter-url=https://books.google.com/books?id=xAPa4WDzAnQC&pg=PA324 |edition=9th |date=14 May 2013 |publisher=John Wiley & Sons |isbn=9781118685907 |pages=323–325 |chapter=Opioid Analgesic Drugs |access-date=25 December 2021 |archive-date=1 May 2023 |archive-url=https://web.archive.org/web/20230501050348/https://books.google.com/books?id=xAPa4WDzAnQC&pg=PA324 |url-status=live }}</ref><ref>{{cite journal | vauthors = Steagall PV, Ruel HL, Yasuda T, Monteiro BP, Watanabe R, Evangelista MC, Beaudry F | title = Pharmacokinetics and analgesic effects of intravenous, intramuscular or subcutaneous buprenorphine in dogs undergoing ovariohysterectomy: a randomized, prospective, masked, clinical trial | journal = BMC Veterinary Research | volume = 16 | issue = 1 | pages = 154 | date = May 2020 | pmid = 32448336 | pmc = 7245774 | doi = 10.1186/s12917-020-02364-w | doi-access = free }}</ref>

== References ==

{{Reflist}}

== External links ==

* {{cite magazine | vauthors = McGray D | date = 1 April 2005 | url = https://www.wired.com/2005/04/bupe/ | title = The bitter pill | magazine = [[Wired (magazine)|Wired]] }}

* {{cite magazine | vauthors = Wood G | date = 7 May 2013 | url = https://newrepublic.com/article/113051/georgias-war-drugs-how-its-subutex-addiction-ended | title = Subu Must Die – How a nation of junkies went cold turkey | magazine = [[The New Republic|New Republic]] }}

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