View source for Diazepam

{{Short description|Benzodiazepine sedative}}
{{Use American English|date=December 2022}}
{{Use dmy dates|date=February 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 443634166
| image = Diazepam structure.svg
| image_class = skin-invert-image
| width = 200
| alt = 
| caption = 
| image2 = Diazepam-from-xtal-3D-balls.png
| alt2 = <!-- Clinical data -->
| pronounce = {{IPAc-en|d|aɪ|ˈ|æ|z|ᵻ|p|æ|m}} {{respell|dy|AZ|ip|am}}
| tradename = Valium, others<ref name="auto"/>
| Drugs.com = {{drugs.com|monograph|diazepam}}
| MedlinePlus = a682047
| DailyMedID = Diazepam
| pregnancy_AU = C
| pregnancy_AU_comment = <ref name="Valium PI" />
| pregnancy_category = 
| dependency_liability = High<ref name="Edmunds-2013">{{cite book |vauthors=Edmunds M, Mayhew M |year=2013 |title=Pharmacology for the Primary Care Provider |url=https://books.google.com/books?id=8FwdEsvnw8oC&pg=PA545 |edition=4th |publisher=Mosby |page=545 |isbn=978-0-323-08790-2 |access-date=13 July 2020 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114192427/https://books.google.com/books?id=8FwdEsvnw8oC&pg=PA545 |url-status=live }}</ref>
| addiction_liability = Moderate<ref name="Cambridge University Press-2010">{{cite book|title=Clinical Addiction Psychiatry|date=2010|publisher=Cambridge University Press|isbn=978-1-139-49169-3|page=156|url=https://books.google.com/books?id=xD-R7Z27UBEC&pg=PA156|url-status=live|archive-url=https://web.archive.org/web/20170908135445/https://books.google.com/books?id=xD-R7Z27UBEC&pg=PA156|archive-date=8 September 2017}}</ref><ref name="Ries-2009">{{cite book| vauthors = Ries RK |title= Principles of addiction medicine|date=2009|publisher=Wolters Kluwer/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-7477-2|page=106|edition=4|url=https://books.google.com/books?id=j6GGBud8DXcC&pg=PA106|url-status=live|archive-url=https://web.archive.org/web/20170908135444/https://books.google.com/books?id=j6GGBud8DXcC&pg=PA106|archive-date=8 September 2017}}</ref>
| routes_of_administration = [[Oral administration|Oral]], [[Intramuscular injection|intramuscular]], [[Intravenous therapy|intravenous]], [[Rectal administration|rectal]], [[Nasal administration|intranasal]],<ref name="valtoco">{{cite web | title=Valtoco – diazepam spray | website=DailyMed | date=13 January 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a8bcc90-68fa-474d-832c-0df01e825f39 | access-date=13 February 2020 | archive-date=1 August 2020 | archive-url=https://web.archive.org/web/20200801111151/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a8bcc90-68fa-474d-832c-0df01e825f39 | url-status=live }}</ref> [[Buccal administration|buccal]]
| class = [[Benzodiazepine]]
| ATC_prefix = N05
| ATC_suffix = BA01
| ATC_supplemental = <!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref name="Valium PI">{{cite web | title=Valium | website=NPS MedicineWise | date=31 January 2020 | url=https://www.nps.org.au/medicine-finder/valium-tablets#full-pi | access-date=9 January 2023 | archive-date=29 July 2020 | archive-url=https://web.archive.org/web/20200729210249/https://www.nps.org.au/medicine-finder/valium-tablets#full-pi | url-status=live }}</ref>
| legal_BR = B1
| legal_BR_comment = 
| legal_CA = Schedule IV
| legal_CA_comment = 
| legal_DE = Rx-only/Anlage III
| legal_DE_comment = 
| legal_NZ = Class C5
| legal_NZ_comment = 
| legal_UK = Class C<ref>{{cite web |url=https://www.legislation.gov.uk/ukpga/1971/38/schedule/2/part/III/paragraph/1|title=Misuse of Drugs Act 1971}}</ref>
| legal_UK_comment = <ref name="Diazepam SmPC" /><ref name="Diazepam Injection SmPC">{{cite web | title=Diazepam Injection BP Summary of Product Characteristics (SmPC) | website=emc | date=17 January 2022 | url=https://www.medicines.org.uk/emc/product/6274/smpc | access-date=11 February 2024 | archive-date=25 January 2023 | archive-url=https://web.archive.org/web/20230125104650/https://www.medicines.org.uk/emc/product/6274/smpc | url-status=live }}</ref>
| legal_US = Schedule IV
| legal_US_comment = <ref name="Valium FDA label" /><ref>{{cite web | title=Libervant- diazepam film | website=DailyMed | date=27 April 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=12527569-8eb3-4624-b3c0-5c0e0c5f88c9 | access-date=18 May 2024}}</ref>
| legal_EU = 
| legal_EU_comment = 
| legal_UN = Psychotropic schedule IV
| legal_UN_comment = 
| legal_status = Rx-only
<!-- | legal_status      = SE: Förteckning IV -->

<!-- Pharmacokinetic data -->| bioavailability = [[Oral administration|Oral]]: 76% (64–97%)<br />[[Rectal administration|Rectal]]: 81% (62–98%)<ref name="pmid7059446">{{cite journal | vauthors = Dhillon S, Oxley J, Richens A | title = Bioavailability of diazepam after intravenous, oral and rectal administration in adult epileptic patients | journal = British Journal of Clinical Pharmacology | volume = 13 | issue = 3 | pages = 427–32 | date = March 1982 | pmid = 7059446 | pmc = 1402110 | doi = 10.1111/j.1365-2125.1982.tb01397.x }}</ref>
| protein_bound = 
| metabolism = [[Liver]] – [[CYP2B6]] (minor route) to [[desmethyldiazepam]], [[CYP2C19]] (major route) to inactive metabolites, [[CYP3A4]] (major route) to [[temazepam]]
| metabolites = * [[Temazepam]]<ref>{{cite book | vauthors = Goodkin HP | date = 2010 | chapter = Diazepam | veditors = Panayiotopoulos CP | title = Atlas of Epilepsies | pages = 1727–1731 | publisher = Springer | location = London | doi = 10.1007/978-1-84882-128-6_263 | isbn = 978-1-84882-128-6 }}</ref>
* [[Oxazepam]]<ref>{{cite journal| title=Pharmacokinetics of Diazepam and Its Metabolites in Urine of Chinese Participants | journal=Drugs in R&D | date=2022 | volume=22 | issue=1 | pages=43–50 | doi=10.1007/s40268-021-00375-y | pmid=35099786 | pmc=8885946 | vauthors = Wang LL, Ren XX, He Y, Cui GF, Liu JJ, Jia J, Cao J, Liu Y, Cong B, Wei ZW, Yun KM }}</ref>
* [[Nordiazepam]]<ref>{{cite journal| title=Pharmacokinetics of Diazepam and Its Metabolites in Urine of Chinese Participants | journal=Drugs in R&D | date=2022 | volume=22 | issue=1 | pages=43–50 | doi=10.1007/s40268-021-00375-y | pmid=35099786 | pmc=8885946 | vauthors = Wang LL, Ren XX, He Y, Cui GF, Liu JJ, Jia J, Cao J, Liu Y, Cong B, Wei ZW, Yun KM }}</ref>
| onset = 15-60 minutes orally and 1-3 minutes IV<ref>{{cite web|url=https://www.ncbi.nlm.nih.gov/books/NBK537022/#:~:text=15-60 minutes}}</ref>
| elimination_half-life = ({{Val|50|u=hour}}); {{Val|20|-|100|u=hour}} ({{Val|32|-|200|u=hour}} for main active metabolite desmethyldiazepam)<ref name="Valium FDA label" /><ref name="Diazepam SmPC">{{cite web | title=Diazepam Tablets BP {{Val|10|u=mg}} – Summary of Product Characteristics (SmPC) | website=(emc) | date=16 September 2019 | url=https://www.medicines.org.uk/emc/product/4522/smpc | access-date=25 July 2020 | archive-date=25 July 2020 | archive-url=https://web.archive.org/web/20200725234327/https://www.medicines.org.uk/emc/product/4522/smpc }}</ref><ref name="Diazepam Injection SmPC" />
| duration_of_action = 
| excretion = [[Kidney]]

<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 439-14-5
| CAS_supplemental = 
| PubChem = 3016
| IUPHAR_ligand = 3364
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB00829
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2908
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = Q3JTX2Q7TU
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00293
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 49575
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 12
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = <!-- Chemical and physical data -->
| IUPAC_name = 7-chloro-1-methyl-5-phenyl-3''H''-1,4-benzodiazepin-2-one
| C = 16
| H = 13
| Cl = 1
| N = 2
| O = 1
| SMILES = c1ccccc1C2=NCC(=O)N(C)c3ccc(Cl)cc23
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C16H13ClN2O/c1-19-14-8-7-12(17)9-13(14)16(18-10-15(19)20)11-5-3-2-4-6-11/h2-9H,10H2,1H3
| StdInChI_comment = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = AAOVKJBEBIDNHE-UHFFFAOYSA-N
| density = 
| density_notes = 
| melting_point = 
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}

<!-- Definition and medical uses -->
'''Diazepam''', sold under the brand name '''Valium''' among others, is a medication of the [[benzodiazepine]] family that acts as an [[anxiolytic]].<ref name="pmid24552479"/> It is used to treat a range of conditions, including [[anxiety disorder|anxiety]], [[seizure]]s, [[alcohol withdrawal syndrome]], [[muscle spasms]], [[insomnia]], and [[restless legs syndrome]].<ref name="pmid24552479"/> It may also be used to cause [[amnesia|memory loss]] during certain medical procedures.<ref name="PubChem">{{Cite web |title=Diazepam |url=https://pubchem.ncbi.nlm.nih.gov/compound/3016 |access-date=2 February 2024 |work=PubChem |publisher=U.S. National Library of Medicine}}</ref><ref name=AHFS2015/> It can be taken [[Oral administration|orally]] (by mouth), as a [[suppository]] inserted into the rectum, [[Intramuscular injection|intramuscularly]] (injected into muscle), [[Intravenous therapy|intravenously]] (injection into a vein) or used as a [[nasal spray]].<ref name=valtoco/><ref name=AHFS2015/> When injected intravenously, effects begin in one to five minutes and last up to an hour.<ref name=AHFS2015>{{cite web|title=Diazepam|url=https://www.drugs.com/monograph/diazepam.html|publisher=The American Society of Health-System Pharmacists|access-date=5 June 2015|url-status=live|archive-url=https://web.archive.org/web/20150630144220/http://www.drugs.com/monograph/diazepam.html|archive-date=30 June 2015}}</ref> When taken by mouth, effects begin after 15 to 60 minutes.<ref name="pmid30725707">{{cite book|vauthors=Dhaliwal JS, Saadabadi A|chapter=Diazepam|date=September 2022|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK537022/|title=StatPearls [Internet]|publisher=StatPearls Publishing|pmid=30725707|access-date=13 October 2019|archive-date=8 March 2021|archive-url=https://web.archive.org/web/20210308201231/http://www.ncbi.nlm.nih.gov/books/NBK537022/|url-status=live}}</ref>

<!-- Adverse effects and mechanism -->
Common side effects include sleepiness and trouble with coordination.<ref name="Valium FDA label">{{cite web | title=Valium – diazepam tablet | website=DailyMed | date=8 November 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=554baee5-b171-4452-a50a-41a0946f956c | access-date=30 December 2019 | archive-date=28 June 2019 | archive-url=https://web.archive.org/web/20190628202244/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=554baee5-b171-4452-a50a-41a0946f956c | url-status=live }}</ref><ref name="AHFS2015" /> Serious side effects are rare.<ref name="pmid24552479" /> They include increased risk of [[suicide]], decreased breathing, and a paradoxical increased risk of seizures if used too frequently in those with [[epilepsy]].<ref name="pmid24552479" /><ref name="AHFS2015" /><ref name="pmid28257172">{{cite journal | vauthors = Dodds TJ | title = Prescribed Benzodiazepines and Suicide Risk: A Review of the Literature | journal = The Primary Care Companion for CNS Disorders | volume = 19 | issue = 2 | date = March 2017 | pmid = 28257172 | doi = 10.4088/PCC.16r02037 | doi-access = free }}</ref> Occasionally, excitement or [[Psychomotor agitation|agitation]] may occur.<ref name="pmid18384456">{{cite journal | vauthors = Riss J, Cloyd J, Gates J, Collins S | title = Benzodiazepines in epilepsy: pharmacology and pharmacokinetics | journal = Acta Neurologica Scandinavica | volume = 118 | issue = 2 | pages = 69–86 | date = August 2008 | pmid = 18384456 | doi = 10.1111/j.1600-0404.2008.01004.x | s2cid = 24453988 | doi-access = free }}</ref><ref name="Perkin-2008">{{cite book| vauthors = Perkin RM |title=Pediatric hospital medicine: textbook of inpatient management|date=2008|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-0-7817-7032-3|page=862|edition=2nd|url=https://books.google.com/books?id=sV6-ifUGoMYC&pg=PA862}}</ref> [[Long-term effects of benzodiazepines|Long-term use]] can result in [[drug tolerance|tolerance]], [[benzodiazepine dependence|dependence]], and withdrawal symptoms on dose reduction.<ref name="pmid24552479" /> Abrupt stopping after long-term use can be potentially dangerous.<ref name="pmid24552479" /> After stopping, [[cognitive]] problems may persist for six months or longer.<ref name="pmid18384456" /> It is not recommended during pregnancy or breastfeeding.<ref name="AHFS2015" /> Its mechanism of action works by increasing the effect of the neurotransmitter [[gamma-Aminobutyric acid|''gamma''-aminobutyric acid]] (GABA).<ref name="pmid18384456" />

<!-- History, society, and culture -->Diazepam was patented in 1959 by [[Hoffmann-La Roche]].<ref name="pmid24552479" /><ref name="Fis2006">{{cite book |vauthors=Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=535 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA535 |access-date=5 June 2020 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114172419/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA535 |url-status=live }}</ref><ref name="worldwide.espacenet.com-1968">{{cite patent |country=US |number=3371085 |status=patent |title=5-ARYL-3H-1,4-BENZODIAZEPIN-2(1H)-ONES |pubdate=1968-02-27 |gdate=1968-02-27 |fdate=1961-11-20 |pridate=1959-12-10 | inventor = Sternbach LH, Reeder E |assign1=Hoffmann La Roche AG |url=https://patents.google.com/patent/US3371085A/en?oq=us+3371085 }}</ref> It has been one of the most frequently prescribed medications in the world since its launch in 1963.<ref name="pmid24552479" /> In the United States it was the best-selling medication between 1968 and 1982, selling more than 2{{nbsp}}billion tablets in 1978 alone.<ref name="pmid24552479" /> In 2023, it was the 183rd most commonly prescribed medication in the United States, with more than 2{{nbsp}}million prescriptions.<ref name="Top 300">{{cite web | title=Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Diazepam Drug Usage Statistics, United States, 2013 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Diazepam | access-date = 19 August 2025 }}</ref> In 1985, the patent ended, and there are more than 500 brands available on the market.<ref name="pmid24552479">{{cite journal | vauthors = Calcaterra NE, Barrow JC | title = Classics in chemical neuroscience: diazepam (valium) | journal = ACS Chemical Neuroscience | volume = 5 | issue = 4 | pages = 253–60 | date = April 2014 | pmid = 24552479 | pmc = 3990949 | doi = 10.1021/cn5000056 }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref>

==Medical uses==
[[File:Diazepam(Valium) DOJ.jpg|thumb|upright|Diazepam tablets (10, 5, and {{Val|2|u=mg}})]]

Diazepam is mainly used to treat anxiety, insomnia, panic attacks, and symptoms of acute alcohol withdrawal. It is also used as a [[premedication]] for inducing sedation, anxiolysis, or amnesia before certain medical procedures (e.g., [[endoscopy]]).<ref name="DrugBank">{{cite web | work = Drug Bank | title = Diazepam |url=http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD00642.txt |archive-url=https://web.archive.org/web/20061224154141/http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD00642.txt |archive-date=24 December 2006 }}</ref><ref name="pmid16053464">{{cite journal | vauthors = Bråthen G, Ben-Menachem E, Brodtkorb E, Galvin R, Garcia-Monco JC, Halasz P, Hillbom M, Leone MA, Young AB | title = EFNS guideline on the diagnosis and management of alcohol-related seizures: report of an EFNS task force | journal = European Journal of Neurology | volume = 12 | issue = 8 | pages = 575–81 | date = August 2005 | pmid = 16053464 | doi = 10.1111/j.1468-1331.2005.01247.x | s2cid = 25904252 | doi-access = free }}</ref> In 2020, it was approved for use in the United States as a [[nasal spray]] to interrupt seizure activity in people with [[epilepsy]].<ref name=valtoco/><ref name="drugs.com">{{cite web |title=FDA approves Valtoco |url=https://www.drugs.com/newdrugs/fda-approves-valtoco-diazepam-nasal-seizure-rescue-5141.html |publisher=Drugs.com |access-date=18 February 2020 |date=13 January 2020 |archive-date=18 February 2020 |archive-url=https://web.archive.org/web/20200218141202/https://www.drugs.com/newdrugs/fda-approves-valtoco-diazepam-nasal-seizure-rescue-5141.html |url-status=live }}</ref> Diazepam is the most commonly used benzodiazepine for "tapering" benzodiazepine dependence due to the drug's comparatively long half-life, allowing for more efficient dose reduction. Benzodiazepines have a relatively low toxicity in overdose.<ref name="pmid18384456" />

Diazepam has several uses, including:
* Treatment of anxiety, [[panic attack]]s, and states of [[Psychomotor agitation|agitation]]<ref name="DrugBank" /><ref name="NPS MedicineWise">{{cite web|url=https://www.nps.org.au/medicine-finder/valium-tablets|title=Valium Tablets|website=NPS MedicineWise|access-date=29 August 2019|archive-date=29 July 2020|archive-url=https://web.archive.org/web/20200729210249/https://www.nps.org.au/medicine-finder/valium-tablets|url-status=live}}</ref>
* Treatment of neurovegetative symptoms associated with [[Vertigo (medical)|vertigo]]<ref name="pmid15045617">{{cite journal | vauthors = Cesarani A, Alpini D, Monti B, Raponi G | s2cid = 25105327 | title = The treatment of acute vertigo | journal = Neurological Sciences | volume = 25 | issue = Suppl 1 | pages = S26-30 | date = March 2004 | pmid = 15045617 | doi = 10.1007/s10072-004-0213-8 }}</ref>
* Treatment of the symptoms of [[Alcohol withdrawal syndrome|alcohol]], [[Opioid withdrawal|opiate]], and [[benzodiazepine withdrawal]]<ref name="DrugBank" /><ref name="pmid19062773">{{cite journal | vauthors = Lader M, Tylee A, Donoghue J | s2cid = 113206 | title = Withdrawing benzodiazepines in primary care | journal = CNS Drugs | volume = 23 | issue = 1 | pages = 19–34 | year = 2009 | pmid = 19062773 | doi = 10.2165/0023210-200923010-00002 }}</ref>
* Short-term treatment of [[insomnia]]<ref name="DrugBank" />
* Treatment of muscle spasms
* Treatment of [[tetanus]], together with other measures of intensive treatment<ref name="pmid14974046">{{cite journal | vauthors = Okoromah CN, Lesi FE | title = Diazepam for treating tetanus | journal = The Cochrane Database of Systematic Reviews | issue = 1 | article-number = CD003954 | year = 2004 | volume = 2010 | pmid = 14974046 | doi = 10.1002/14651858.CD003954.pub2 | pmc = 8759227 | veditors = Okoromah CA }}</ref>
* Adjunctive treatment of spastic muscular [[paresis]] (paraplegia/tetraplegia) caused by cerebral or [[spinal cord]] conditions such as [[stroke]], [[multiple sclerosis]], or spinal cord injury (long-term treatment is coupled with other rehabilitative measures)<ref name="RXL.Indications" />
* Palliative treatment of [[stiff person syndrome]]<ref name="Drugs.com">{{cite web | publisher = Thomson Healthcare (Micromedex) | date= March 2000 | url= https://www.drugs.com/pdr/diazepam.html | title= Diazepam | work= Prescription Drug Information | access-date= 11 March 2006 | archive-url= https://web.archive.org/web/20060619102054/http://www.drugs.com/pdr/DIAZEPAM.html | archive-date= 19 June 2006 }}</ref>
* Pre- or postoperative sedation, anxiolysis or [[amnesia]] (e.g., before endoscopic or surgical procedures)<ref name="RXL.Indications" />
* Treatment of complications with [[stimulant]] overdoses and psychosis, such as [[cocaine]] or [[methamphetamine]]<ref name="Inchem" />
Used in the treatment of organophosphate poisoning and reduces the risk of seizure-induced brain and cardiac damage.
* Preventive treatment of [[oxygen toxicity]] during [[hyperbaric oxygen therapy]]<ref name="Hyperbaric">{{cite book | vauthors = Kindwall EP, Whelan HT | year = 1999 | title = Hyperbaric Medicine Practice | edition = 2nd | publisher = Best Publishing Company | isbn = 978-0-941332-78-1 }}</ref>

Dosages are typically determined on an individual basis, depending on the condition being treated, the severity of symptoms, the patient's body weight, and any other conditions the person may have.<ref name="Inchem" />

===Seizures===
Intravenous diazepam and [[lorazepam]] are first-line treatments for status epilepticus.<ref name="pmid18384456"/><ref name="pmid16179702">{{cite journal | vauthors = Walker M | title = Status epilepticus: an evidence based guide | journal = BMJ | volume = 331 | issue = 7518 | pages = 673–7 | date = September 2005 | pmid = 16179702 | pmc = 1226249 | doi = 10.1136/bmj.331.7518.673 }}</ref> However, intravenous [[lorazepam]] has advantages over intravenous diazepam, including a higher rate of terminating seizures and a more prolonged anticonvulsant effect. Diazepam gel was better than placebo gel in reducing the risk of non-cessation of seizures.<ref name="pmid25207925">{{cite journal | vauthors = Prasad M, Krishnan PR, Sequeira R, Al-Roomi K | title = Anticonvulsant therapy for status epilepticus | journal = The Cochrane Database of Systematic Reviews | volume = 2014 | issue = 9 | article-number = CD003723 | date = September 2014 | pmid = 25207925 | doi = 10.1002/14651858.CD003723.pub3 | pmc = 7154380 }}</ref> Diazepam is rarely used for the long-term treatment of [[epilepsy]] because tolerance to its anticonvulsant effects usually develops within six to twelve months of treatment, effectively rendering it useless for that purpose.<ref name="Inchem" /><ref name="pmid10030438">{{cite journal | vauthors = Isojärvi JI, Tokola RA | title = Benzodiazepines in the treatment of epilepsy in people with intellectual disability | journal = Journal of Intellectual Disability Research | volume = 42 | issue = Suppl 1 | pages = 80–92 | date = December 1998 | pmid = 10030438 }}</ref>

The anticonvulsant effects of diazepam can help in the treatment of seizures due to a drug overdose or chemical toxicity as a result of exposure to [[sarin]], [[VX (nerve agent)|VX]], or [[soman]] (or other [[organophosphate]] poisons), [[lindane]], [[chloroquine]], [[physostigmine]], or [[pyrethroid]]s.<ref name="Inchem" /><ref name="pmid15521192">{{cite book | vauthors = Bajgar J | title = Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment | volume = 38 | pages = 151–216 | year = 2004 | pmid = 15521192 | doi = 10.1016/S0065-2423(04)38006-6 | isbn = 978-0-12-010338-6 | series = Advances in Clinical Chemistry }}</ref>

Diazepam is sometimes used intermittently for the prevention of [[febrile seizure]]s that may occur in children under five years of age.<ref name="pmid18384456" /> Recurrence rates are reduced, but side effects are common, and the decision to treat febrile seizures (which are benign in nature) with medication uses these factors as part of the evaluation.<ref name="pmid34131913">{{cite journal | vauthors = Offringa M, Newton R, Nevitt SJ, Vraka K | title = Prophylactic drug management for febrile seizures in children | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 6 | article-number = CD003031 | date = June 2021 | pmid = 34131913 | pmc = 8207248 | doi = 10.1002/14651858.CD003031.pub4 }}</ref> Long-term use of diazepam for the management of epilepsy is not recommended;{{by whom|date=December 2024}} however, a subgroup of individuals with treatment-resistant epilepsy benefit from long-term benzodiazepines, and for such individuals, [[clorazepate]] has been recommended due to its slower onset of tolerance to the anticonvulsant effects.<ref name="pmid18384456" />

===Alcohol withdrawal===
Because of its relatively long duration of action and evidence of safety and efficacy, diazepam is preferred over other benzodiazepines for the treatment of persons experiencing moderate to severe alcohol withdrawal.<ref name="pmid28101764">{{cite journal |vauthors=Weintraub SJ |s2cid=42610220 |title=Diazepam in the Treatment of Moderate to Severe Alcohol Withdrawal |journal=CNS Drugs |volume=31 |issue=2 |pages=87–95 |date=February 2017 |pmid=28101764 |doi=10.1007/s40263-016-0403-y }}</ref> An exception to this is when a medication is required [[intramuscular]] in which case either [[lorazepam]] or [[midazolam]] is recommended.<ref name="pmid28101764"/>

===Other===
Diazepam is used for the emergency treatment of [[eclampsia]] when [[Intravenous therapy|IV]] [[magnesium sulfate]] and blood-pressure control measures have failed.<ref name="pmid15474770">{{cite journal | vauthors = Kaplan PW | title = Neurologic aspects of eclampsia | journal = Neurologic Clinics | volume = 22 | issue = 4 | pages = 841–61 | date = November 2004 | pmid = 15474770 | doi = 10.1016/j.ncl.2004.07.005 | doi-access = free }}</ref><ref name="pmid15749066">{{cite journal | vauthors = Duley L | title = Evidence and practice: the magnesium sulphate story | journal = Best Practice & Research. Clinical Obstetrics & Gynaecology | volume = 19 | issue = 1 | pages = 57–74 | date = February 2005 | pmid = 15749066 | doi = 10.1016/j.bpobgyn.2004.10.010 }}</ref> Benzodiazepines do not have any pain-relieving properties themselves and are generally recommended to be avoided in individuals with pain.<ref name="pmid19259638">{{cite journal | vauthors = Zeilhofer HU, Witschi R, Hösl K | s2cid = 5614111 | title = Subtype-selective GABAA receptor mimetics—novel antihyperalgesic agents? | journal = Journal of Molecular Medicine | volume = 87 | issue = 5 | pages = 465–9 | date = May 2009 | pmid = 19259638 | doi = 10.1007/s00109-009-0454-3 | hdl = 20.500.11850/20278 | url = https://www.zora.uzh.ch/id/eprint/17933/10/ZORA_NL_17933.pdf | hdl-access = free | access-date = 13 December 2019 | archive-date = 29 July 2020 | archive-url = https://web.archive.org/web/20200729222620/https://www.zora.uzh.ch/id/eprint/17933/10/ZORA_NL_17933.pdf | url-status = live }}</ref> However, benzodiazepines such as diazepam can be used for their muscle-relaxant properties to alleviate pain caused by muscle spasms and various [[dystonia]]s, including [[blepharospasm]].<ref name="pmid16248394">{{cite journal | vauthors = Mezaki T, Hayashi A, Nakase H, Hasegawa K | title = [Therapy of dystonia in Japan] | language = ja | journal = Rinsho Shinkeigaku = Clinical Neurology | volume = 45 | issue = 9 | pages = 634–42 | date = September 2005 | pmid = 16248394 }}</ref><ref name="pmid12235832">{{cite journal | vauthors = Kachi T | title = [Medical treatment of dystonia] | language = ja | journal = Rinsho Shinkeigaku = Clinical Neurology | volume = 41 | issue = 12 | pages = 1181–2 | date = December 2001 | pmid = 12235832 }}</ref> Tolerance often develops to the [[muscle relaxant]] effects of benzodiazepines such as diazepam.<ref name="pmid16639148">{{cite journal | vauthors = Ashton H | title = The diagnosis and management of benzodiazepine dependence | journal = Current Opinion in Psychiatry | volume = 18 | issue = 3 | pages = 249–55 | date = May 2005 | pmid = 16639148 | doi = 10.1097/01.yco.0000165594.60434.84 | s2cid = 1709063 | url = http://www.benzo.org.uk/amisc/ashdiag.pdf | access-date = 13 May 2010 | archive-date = 8 August 2017 | archive-url = https://web.archive.org/web/20170808161930/http://www.benzo.org.uk/amisc/ashdiag.pdf | url-status = live }}</ref> [[Baclofen]] is sometimes used as an alternative to diazepam.<ref name="pmid9929772">{{cite journal |vauthors=Mañon-Espaillat R, Mandel S |title=Diagnostic Algorithms for Neuromuscular Diseases |journal=Clinics in Podiatric Medicine and Surgery |volume=16 |issue=1 |pages=67–79 |date=January 1999 |doi=10.1016/S0891-8422(23)00935-7 |pmid=9929772 |s2cid=12493035 }}</ref>

===Availability===
Diazepam is marketed in over 500 brands throughout the world.<ref name="ILAE">{{cite web| url=http://www.ilae.org/Visitors/Centre/AEDs/index.cfm| title=International AED Database| access-date=16 September 2009| publisher=ILAE| archive-url=https://web.archive.org/web/20080509073033/http://www.ilae.org/Visitors/Centre/AEDs/index.cfm| archive-date=9 May 2008}}</ref> It is supplied in oral, injectable, inhalation, and rectal forms.<ref name="Inchem" /><ref name="ElephantCare">{{cite web |year=2005 |title=Diazepam |url=http://www.elephantcare.org/Drugs/diazepam.htm |archive-url=https://web.archive.org/web/20050908214617/http://www.elephantcare.org/Drugs/diazepam.htm |archive-date=8 September 2005 |work=The Elephant Formulary |publisher=Elephant Care International |vauthors=Mikota SK, Plumb DC}}</ref><ref name="US Patent 6,805,853-2004">{{cite web |title=Delivery of diazepam through an inhalation route |url=http://www.pharmcast.com/Patents100/Yr2004/Oct2004/101904/6805853_Diazepam101904.htm |work=US Patent 6,805,853 |publisher=PharmCast.com |date=19 October 2004 |access-date=12 December 2014 |archive-url=https://web.archive.org/web/20151017131331/http://www.pharmcast.com/Patents100/Yr2004/Oct2004/101904/6805853_Diazepam101904.htm |archive-date=17 October 2015 }}</ref>

The [[United States military]] employs a specialized diazepam preparation known as Convulsive Antidote, Nerve Agent ({{vanchor|CANA}}), which contains diazepam. One CANA kit is typically issued to service members, along with three [[Mark I NAAK]] kits, when operating in circumstances where chemical weapons in the form of [[nerve agent]]s are considered a potential hazard. Both of these kits deliver drugs using [[autoinjector]]s. They are intended for use in "buddy aid" or "self-aid" administration of the drugs in the field before [[decontamination]] and delivery of the patient to definitive medical care.<ref name="Medical Management-2000">[[United States Army Medical Research Institute of Chemical Defense|U.S. Army Medical Research Institute of Chemical Defense]], ''Medical Management of Chemical Casualties Handbook'', Third Edition (June 2000), [[Aberdeen Proving Ground]], MD, pp. 118–126.</ref>

==Contraindications==
Use of diazepam is avoided, when possible, in individuals with:<ref name="Epocrates Online">{{cite web | url = https://online.epocrates.com/u/103193/diazepam/Contraindications+Cautions | title = Diazepam Contraindications and Cautions | access-date = 16 December 2008 | author = Epocrates | publisher = Epocrates Online | location = US | url-status=live | archive-url = https://web.archive.org/web/20110710195415/https://online.epocrates.com/u/103193/diazepam/Contraindications+Cautions | archive-date = 10 July 2011 }}</ref>
* [[Ataxia]]
* Severe [[hypoventilation]]
* Acute narrow-angle [[glaucoma]]
* Severe [[hepatic]] deficiencies ([[hepatitis]] and liver [[cirrhosis]] decrease elimination by a factor of two)
* Severe [[renal]] deficiencies (for example, patients on [[Kidney dialysis|dialysis]])
* Liver disorders
* Severe [[sleep apnea]]
* Severe [[clinical depression|depression]], particularly when accompanied by suicidal tendencies
* [[Psychosis]]
* [[Pregnancy]] or [[breastfeeding]]<ref name="pmid36521643">{{cite journal | vauthors = Aparecido da Silva Junior C, Marques DA, Patrone LG, Biancardi V, Bícego KC, Gargaglioni LH | title = Intra-uterine diazepam exposure decreases the number of catecholaminergic and serotonergic neurons of neonate rats | journal = Neuroscience Letters | article-number = 137014 | date = December 2022 | volume = 795 | pmid = 36521643 | doi = 10.1016/j.neulet.2022.137014 | s2cid = 254555032 | doi-access = free }}</ref>
* Caution required in elderly or debilitated patients
* [[Coma]] or shock
* Abrupt discontinuation of therapy
* Acute intoxication with [[alcohol (drug)|alcohol]], [[narcotic]]s, or other psychoactive substances (with the exception of hallucinogens or some stimulants, where it is occasionally used as a treatment for overdose)
* History of alcohol or [[drug dependence]]
* [[Myasthenia gravis]], an [[autoimmune disorder]] causing marked fatiguability
* [[Hypersensitivity]] or [[allergy]] to any drug in the benzodiazepine class

===Abuse and special populations===
* Benzodiazepine abuse and misuse are guarded against when prescribed to those with alcohol or drug dependencies or who have [[psychiatric disorders]].<ref name="pmid19900604">{{cite journal | vauthors = Authier N, Balayssac D, Sautereau M, Zangarelli A, Courty P, Somogyi AA, Vennat B, Llorca PM, Eschalier A | title = Benzodiazepine dependence: focus on withdrawal syndrome | journal = Annales Pharmaceutiques Françaises | volume = 67 | issue = 6 | pages = 408–13 | date = November 2009 | pmid = 19900604 | doi = 10.1016/j.pharma.2009.07.001 }}</ref>
* Pediatric patients
** For those less than 18 years of age, this treatment is usually not indicated, except for treatment of epilepsy, and pre-or postoperative treatment. The smallest possible effective dose is typically used for this group of patients.<ref name="PDRhealth" />
** Under 6 months of age, safety and effectiveness have not been established; diazepam is not given to those in this age group.<ref name="Drugs.com" /><ref name="PDRhealth" />
* Elderly and very ill patients can experience [[apnea]] or [[cardiac arrest]]. Concomitant use of other central nervous system depressants increases this risk. The smallest possible effective dose is generally used for this group of people.<ref name="PDRhealth" /><ref name="RXL.Caution">{{cite web| date= 24 January 2005| url= http://www.rxlist.com/cgi/generic/diazepam_wcp.htm| title= Diazepam: precautions| work= Rxlist.com| publisher= RxList Inc.| access-date= 10 March 2006| archive-url= https://web.archive.org/web/20060407221843/http://www.rxlist.com/cgi/generic/diazepam_wcp.htm| archive-date= 7 April 2006| df= mdy-all}}</ref> The elderly metabolise benzodiazepines much more slowly than younger adults, and are also more sensitive to the effects of benzodiazepines, even at similar blood plasma levels. Doses of diazepam are recommended to be about half of those given to younger people, and treatment is limited to a maximum of two weeks. Long-acting benzodiazepines such as diazepam are not recommended for the elderly.<ref name="pmid18384456" /> Diazepam can also be dangerous in geriatric patients owing to a significantly increased risk of falls.<ref name="pmid7557666">{{cite journal | vauthors = Shats V, Kozacov S | title = [Falls in the geriatric department: responsibility of the caregiver and the hospital] | language = he | journal = Harefuah | volume = 128 | issue = 11 | pages = 690–3, 743 | date = June 1995 | pmid = 7557666 }}</ref>
* Intravenous or intramuscular injections in hypotensive people or those in shock are administered carefully, and vital signs are closely monitored.<ref name="RXL.Caution" />
* Benzodiazepines such as diazepam are [[lipophilic]] and rapidly penetrate membranes, thus rapidly cross over into the placenta with significant uptake of the drug. Use of benzodiazepines, including diazepam in late pregnancy, especially high doses, can result in [[floppy infant syndrome]].<ref name="pmid6124415">{{cite journal | vauthors = Kanto JH | s2cid = 27014006 | title = Use of benzodiazepines during pregnancy, labour and lactation, with particular reference to pharmacokinetic considerations | journal = Drugs | volume = 23 | issue = 5 | pages = 354–80 | date = May 1982 | pmid = 6124415 | doi = 10.2165/00003495-198223050-00002 }}</ref> Diazepam when taken late in pregnancy, during the [[third trimester]], causes a definite risk of a severe [[benzodiazepine withdrawal syndrome]] in the neonate with symptoms including [[hypotonia]], and reluctance to suck, to [[apnoeic]] spells, [[cyanosis]], and impaired [[metabolic]] responses to cold stress. Floppy infant syndrome and sedation in the newborn may also occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.<ref name="pmid7881198">{{cite journal | vauthors = McElhatton PR | title = The effects of benzodiazepine use during pregnancy and lactation | journal = Reproductive Toxicology | volume = 8 | issue = 6 | pages = 461–75 | year = 1994 | pmid = 7881198 | doi = 10.1016/0890-6238(94)90029-9 | bibcode = 1994RepTx...8..461M }}</ref>

==Adverse effects==
Benzodiazepines, such as diazepam, can cause [[anterograde amnesia]], confusion, and [[sedation]]. The elderly are more prone to diazepam's confusion, amnesia, ataxia, hangover symptoms, and falls. Long-term use of benzodiazepines, such as diazepam, induces tolerance, dependency, and withdrawal syndrome.<ref name="pmid18384456" /> Like other benzodiazepines, diazepam impairs short-term memory and learning new information. Diazepam and other benzodiazepines can produce anterograde amnesia, but not [[retrograde amnesia]], which means information learned before using benzodiazepines is not impaired. Short-term benzodiazepine use does not lead to tolerance, and the elderly are more sensitive to them.<ref name="the_american_psychiatric_publishing_textbook_of_neuropsychia">{{cite book | vauthors = Yudofsky SC, Hales RE | title = The American Psychiatric Publishing Textbook of Neuropsychiatry and Behavioral Neurosciences, Fifth Edition (American Psychiatric Press Textbook of Neuropsychiatry) | url = https://books.google.com/books?id=f5BEk-6yO_4C&pg=PA583 | date = 1 December 2007 | publisher = American Psychiatric Publishing, Inc. | location = US | isbn = 978-1-58562-239-9 | pages = 583–584 | url-status=live | archive-url = https://web.archive.org/web/20160507062907/https://books.google.com/books?id=f5BEk-6yO_4C&pg=PA583 | archive-date = 7 May 2016 }}</ref> Additionally, after stopping benzodiazepines, cognitive problems may last at least six months; it is unclear if these problems last for longer than six months or are permanent. Benzodiazepines may also cause or worsen depression.<ref name="pmid18384456" /> Infusions or repeated intravenous injections of diazepam when managing seizures, for example, may lead to drug toxicity, including respiratory depression, sedation, and [[hypotension]]. Drug tolerance may also develop to infusions of diazepam if it is given for longer than 24 hours.<ref name="pmid18384456" /> Sedatives and sleeping pills, including diazepam, have been associated with an increased risk of death.<ref name="pmid26563222">{{cite journal | vauthors = Kripke DF | s2cid = 7946506 | title = Mortality Risk of Hypnotics: Strengths and Limits of Evidence | journal = Drug Safety | volume = 39 | issue = 2 | pages = 93–107 | date = February 2016 | pmid = 26563222 | doi = 10.1007/s40264-015-0362-0 | url = https://escholarship.org/content/qt08d9f3d5/qt08d9f3d5.pdf?t=nz1gjv | doi-access = free | access-date = 2 September 2019 | archive-date = 14 March 2020 | archive-url = https://web.archive.org/web/20200314025805/https://escholarship.org/content/qt08d9f3d5/qt08d9f3d5.pdf?t=nz1gjv | url-status = live }}</ref>

In September 2020, the U.S. [[Food and Drug Administration]] (FDA) required the [[boxed warning]] be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class.<ref name="U.S. Food and Drug Administration (FDA)-2020">{{cite web | title=FDA expands Boxed Warning to improve safe use of benzodiazepine drug | website=U.S. [[Food and Drug Administration]] (FDA) | date=23 September 2020 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-boxed-warning-updated-improve-safe-use-benzodiazepine-drug-class | access-date=23 September 2020 | archive-date=24 September 2020 | archive-url=https://web.archive.org/web/20200924002523/https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-boxed-warning-updated-improve-safe-use-benzodiazepine-drug-class }} {{PD-notice}}</ref>

Diazepam has a range of side effects common to most benzodiazepines, including:
* Suppression of [[REM sleep]] and [[slow wave sleep]]
* Impaired motor function
** Impaired coordination
** Impaired balance
** [[Dizziness]]
* [[Tachycardia|Reflex tachycardia]]<!-- This term appears numerous times throughout Wikipedia, and yet nowhere is it properly and clearly defined. --><ref name="Cuny.edu" />

Less commonly, [[paradoxical reaction]]s can occur, including nervousness, irritability, excitement, worsening of seizures, insomnia, muscle cramps, changes in [[libido]], <!-- (increased or decreased libido – This is mentioned in "Roche Pharmaceuticals (AUS) – Valium Product Information link" --> and in some cases, rage and violence. These adverse reactions are more likely to occur in children, the elderly, and individuals with a history of a [[substance use disorder]], such as an [[alcohol use disorder]], or a history of aggressive behavior.<ref name="pmid18384456" /><ref name="pmid2826308">{{cite journal | vauthors = Marrosu F, Marrosu G, Rachel MG, Biggio G | title = Paradoxical reactions elicited by diazepam in children with classic autism | journal = Functional Neurology | volume = 2 | issue = 3 | pages = 355–61 | year = 1987 | pmid = 2826308 }}</ref><ref name=next_three>{{cite web | url = http://www.rxlist.com/cgi/generic/diazepam_ad.htm | title = Diazepam: Side Effects | access-date = 26 September 2006 | work = RxList.com | archive-url = https://web.archive.org/web/20061022201314/http://www.rxlist.com/cgi/generic/diazepam_ad.htm | archive-date = 22 October 2006 | df = mdy-all }}</ref><ref name="pmid15029082">{{cite journal | vauthors = Michel L, Lang JP | title = [Benzodiazepines and forensic aspects] | language = fr | journal = L'Encéphale | volume = 29 | issue = 6 | pages = 479–85 | year = 2003 | pmid = 15029082 | url = http://www.masson.fr/masson/portal/bookmark?Global=1&Page=18&MenuIdSelected=106&MenuItemSelected=0&MenuSupportSelected=0&CodeProduct4=539&CodeRevue4=ENC&Path=REVUE/ENC/2003/29/6/ARTICLE11106200473.xml&Locations= | url-status = live | archive-url = https://web.archive.org/web/20071127111542/http://www.masson.fr/masson/portal/bookmark?Global=1&Page=18&MenuIdSelected=106&MenuItemSelected=0&MenuSupportSelected=0&CodeProduct4=539&CodeRevue4=ENC&Path=REVUE%2FENC%2F2003%2F29%2F6%2FARTICLE11106200473.xml&Locations= | archive-date = 27 November 2007 }}</ref> In some people, diazepam may increase the propensity toward self-harming behavior and, in extreme cases, may provoke suicidal tendencies or acts.<ref name="pmid15316710">{{cite journal | vauthors = Berman ME, Jones GD, McCloskey MS | s2cid = 20629702 | title = The effects of diazepam on human self-aggressive behavior | journal = Psychopharmacology | volume = 178 | issue = 1 | pages = 100–6 | date = February 2005 | pmid = 15316710 | doi = 10.1007/s00213-004-1966-8 }}</ref> Very rarely [[dystonia]] can occur.<ref name="pmid1292648">{{cite journal | vauthors = Pérez Trullen JM, Modrego Pardo PJ, Vázquez André M, López Lozano JJ | title = Bromazepam-induced dystonia | journal = Biomedicine & Pharmacotherapy | volume = 46 | issue = 8 | pages = 375–6 | year = 1992 | pmid = 1292648 | doi = 10.1016/0753-3322(92)90306-R }}</ref>

Diazepam may impair the ability to drive vehicles or operate machinery. The impairment is worsened by the consumption of alcohol because both act as [[central nervous system depressants]].<ref name="Drugs.com" />

During therapy, tolerance to the sedative effects usually develops, but not to the anxiolytic and myorelaxant effects.<ref name="pmid14974234">{{cite journal | vauthors = Hriscu A, Gherase F, Năstasă V, Hriscu E | title = [An experimental study of tolerance to benzodiazepines] | journal = Revista Medico-Chirurgicala a Societatii de Medici Si Naturalisti Din Iasi | volume = 106 | issue = 4 | pages = 806–11 | date = October–December 2002 | pmid = 14974234 }}</ref>

Patients with severe attacks of [[apnea]] during sleep may experience [[respiratory depression]] (hypoventilation), leading to respiratory arrest and death.<ref name="pmid31554703">{{cite journal | vauthors = McNicholas WT, Hansson D, Schiza S, Grote L | title = Sleep in chronic respiratory disease: COPD and hypoventilation disorders | journal = European Respiratory Review | volume = 28 | issue = 153 | page = 190064 | date = September 2019 | pmid = 31554703 | doi = 10.1183/16000617.0064-2019 | pmc = 9488904 | s2cid = 203440265 | doi-access = free }}</ref>

Diazepam in doses of {{Val|5|u=mg}} or more causes significant deterioration in [[alertness]] performance combined with increased feelings of sleepiness.<ref name="pmid7675948">{{cite journal | vauthors = Kozená L, Frantik E, Horváth M | s2cid = 2618084 | title = Vigilance impairment after a single dose of benzodiazepines | journal = Psychopharmacology | volume = 119 | issue = 1 | pages = 39–45 | date = May 1995 | pmid = 7675948 | doi = 10.1007/BF02246052 }}</ref>

===Tolerance and withdrawal===
Diazepam, as with other [[benzodiazepine]] drugs, can cause tolerance, physical dependence, [[substance use disorder]], and [[benzodiazepine withdrawal syndrome]]. Withdrawal from diazepam or other benzodiazepines often leads to withdrawal symptoms similar to those seen during barbiturate or alcohol withdrawal. The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms.<ref name="pmid25560429">{{cite journal | vauthors = Best KM, Boullata JI, Curley MA | title = Risk factors associated with iatrogenic opioid and benzodiazepine withdrawal in critically ill pediatric patients: a systematic review and conceptual model | journal = Pediatric Critical Care Medicine | volume = 16 | issue = 2 | pages = 175–83 | date = February 2015 | pmid = 25560429 | pmc = 5304939 | doi = 10.1097/PCC.0000000000000306 }}</ref>

Withdrawal symptoms can occur from standard dosages and also after short-term use, and can range from insomnia and anxiety to more serious symptoms, including seizures and psychosis. Withdrawal symptoms can sometimes resemble pre-existing conditions and be misdiagnosed. Diazepam may produce less intense withdrawal symptoms due to its long [[elimination half-life]].<ref name="pmid28101764"/>

Benzodiazepine treatment is recommended to be discontinued as soon as possible by a slow and gradual dose reduction regimen.<ref name="pmid18384456" /><ref name="pmid6133446">{{cite journal | vauthors = MacKinnon GL, Parker WA | title = Benzodiazepine withdrawal syndrome: a literature review and evaluation | journal = The American Journal of Drug and Alcohol Abuse | volume = 9 | issue = 1 | pages = 19–33 | year = 1982 | pmid = 6133446 | doi = 10.3109/00952998209002608 }}</ref> Tolerance develops to the therapeutic effects of benzodiazepines; for example, tolerance occurs to the anticonvulsant effects and as a result benzodiazepines are not generally recommended for the long-term management of epilepsy. Dose increases may overcome the effects of tolerance, but tolerance may then develop to the higher dose, and adverse effects may increase. The mechanism of tolerance to benzodiazepines includes [[Uncoupling (neuropsychopharmacology)|uncoupling of receptor sites]], alterations in [[gene expression]], [[Receptor down-regulation|down-regulation of receptor sites]], and desensitisation of receptor sites to the effect of GABA. About one-third of individuals who take benzodiazepines for longer than four weeks become dependent and experience withdrawal syndrome on cessation.<ref name="pmid18384456" />

Differences in withdrawal rates (50–100%) vary depending on the patient sample. For example, a random sample of long-term benzodiazepine users typically finds around 50% experience few or no withdrawal symptoms, with the other 50% experiencing notable withdrawal symptoms. Certain select patient groups show a higher rate of notable withdrawal symptoms, up to 100%.<ref name="pmid2576073">{{cite journal | vauthors = Onyett SR | title = The benzodiazepine withdrawal syndrome and its management | journal = The Journal of the Royal College of General Practitioners | volume = 39 | issue = 321 | pages = 160–3 | date = April 1989 | pmid = 2576073 | pmc = 1711840 }}</ref>

[[Rebound anxiety]], more severe than baseline anxiety, is also a common withdrawal symptom when discontinuing diazepam or other benzodiazepines.<ref name="pmid6141609">{{cite journal | vauthors = Chouinard G, Labonte A, Fontaine R, Annable L | s2cid = 32967696 | title = New concepts in benzodiazepine therapy: rebound anxiety and new indications for the more potent benzodiazepines | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 7 | issue = 4–6 | pages = 669–73 | year = 1983 | pmid = 6141609 | doi = 10.1016/0278-5846(83)90043-X }}</ref> Diazepam is therefore only recommended for short-term therapy at the lowest possible dose owing to risks of severe withdrawal problems from low doses even after gradual reduction.<ref name="pmid2891684">{{cite journal | vauthors = Lader M | title = Long-term anxiolytic therapy: the issue of drug withdrawal | journal = The Journal of Clinical Psychiatry | volume = 48 | issue = Suppl | pages = 12–6 | date = December 1987 | pmid = 2891684 }}</ref> The risk of pharmacological dependence on diazepam is significant, and {{clarify span|text= patients experience symptoms of benzodiazepine withdrawal syndrome if it is taken for six weeks or longer. |explain= It's not clear whether this is saying that patients are guaranteed to experience withdrawal, or that it's a notable effect |date=December 2024}}<ref name="pmid2686797">{{cite journal | vauthors = Murphy SM, Owen R, Tyrer P | s2cid = 5024826 | title = Comparative assessment of efficacy and withdrawal symptoms after 6 and 12 weeks' treatment with diazepam or buspirone | journal = The British Journal of Psychiatry | volume = 154 | issue = 4 | pages = 529–34 | date = April 1989 | pmid = 2686797 | doi = 10.1192/bjp.154.4.529 }}</ref> In humans, tolerance to the anticonvulsant effects of diazepam occurs frequently.<ref name="pmid6373234">{{cite journal | vauthors = Loiseau P | title = [Benzodiazepines in the treatment of epilepsy] | journal = L'Encéphale | volume = 9 | issue = 4 Suppl 2 | pages = 287B–292B | year = 1983 | pmid = 6373234 }}</ref>

===Dependence===
Improper or excessive use of diazepam can lead to [[Substance dependence|dependence]]. At a particularly high risk for diazepam misuse, [[substance use disorder]], or dependence are:
* People with a history of a substance use disorder or substance dependence.<ref name="Drugs.com" /><ref name="RXL.Abuse">{{cite web| date= 24 January 2005| url= http://www.rxlist.com/cgi/generic/diazepam_ad.htm#DA| title= Diazepam: abuse and dependence| work= Rxlist.com| publisher= RxList Inc.| access-date= 10 March 2006| archive-url= https://web.archive.org/web/20060216025301/http://www.rxlist.com/cgi/generic/diazepam_ad.htm#DA| archive-date= 16 February 2006| df= mdy-all}}</ref> Research suggests that diazepam may increase motivation for alcohol consumption and cravings in some individuals with a history of problematic drinking.<ref name="pmid15472572">{{cite journal | vauthors = Poulos CX, Zack M | title = Low-dose diazepam primes motivation for alcohol and alcohol-related semantic networks in problem drinkers | journal = Behavioural Pharmacology | volume = 15 | issue = 7 | pages = 503–12 | date = November 2004 | pmid = 15472572 | doi = 10.1097/00008877-200411000-00006 | s2cid = 23040302 }}</ref>
* People with severe personality disorders, such as [[borderline personality disorder]].<ref name="pmid15830732">{{cite journal | vauthors = Vorma H, Naukkarinen HH, Sarna SJ, Kuoppasalmi KI | s2cid = 1366333 | title = Predictors of benzodiazepine discontinuation in subjects manifesting complicated dependence | journal = Substance Use & Misuse | volume = 40 | issue = 4 | pages = 499–510 | year = 2005 | pmid = 15830732 | doi = 10.1081/JA-200052433 }}</ref>

Patients from the aforementioned groups are monitored very closely during therapy for signs of abuse and the development of dependence. Therapy is recommended to be discontinued if any of these signs are noted. If dependence has developed, therapy is still discontinued gradually to avoid severe withdrawal symptoms. Long-term therapy in such instances is not recommended.<ref name="Drugs.com" /><ref name="RXL.Abuse" />

People suspected of being dependent on benzodiazepine drugs are very gradually tapered off the drug. Withdrawals can be life-threatening, particularly when excessive doses have been taken for extended periods. Therefore, equal prudence is used whether dependence has occurred in therapeutic or recreational contexts.<ref name="pmid18983627">{{cite journal | vauthors = Parr JM, Kavanagh DJ, Cahill L, Mitchell G, McD Young R | title = Effectiveness of current treatment approaches for benzodiazepine discontinuation: a meta-analysis | journal = Addiction | volume = 104 | issue = 1 | pages = 13–24 | date = January 2009 | pmid = 18983627 | doi = 10.1111/j.1360-0443.2008.02364.x }}</ref>

Diazepam is seen as a good choice for tapering for those using high doses of other benzodiazepines since it has a long half-life, thus withdrawal symptoms are tolerable.<ref name="Thirtala-2013">{{cite web | vauthors = Thirtala T, Kaur K, Karlapati SK, Lippmann S | url = https://www.mdedge.com/psychiatry/article/77248/addiction-medicine/consider-slow-taper-program-benzodiazepines | title = Consider this slow-taper program for benzodiazepines | work = Current Psychiatry | date = July 2013 | access-date = 29 August 2019 | archive-date = 29 July 2020 | archive-url = https://web.archive.org/web/20200729211831/https://www.mdedge.com/psychiatry/article/77248/addiction-medicine/consider-slow-taper-program-benzodiazepines | url-status = live }}</ref> The process is very slow (usually from 14 to 28 weeks) but is considered safe when done appropriately.<ref name="Tapering Benzodiazepines">{{cite web |title=Tapering Benzodiazepines |url=https://www.smchealth.org/sites/main/files/file-attachments/benzodiazepinetaper08-12-13.pdf |access-date=29 August 2019 |archive-date=13 July 2018 |archive-url=https://web.archive.org/web/20180713180251/http://www.smchealth.org/sites/main/files/file-attachments/benzodiazepinetaper08-12-13.pdf |url-status=live }}</ref>

==Overdose==
{{Main|Benzodiazepine overdose}}
An individual who has consumed too much diazepam typically displays one or more of these symptoms in approximately four hours immediately following a suspected overdose:<ref name="Drugs.com" /><ref name="RXL.Overdose">{{cite web| date= 24 January 2005| url= http://www.rxlist.com/cgi/generic/diazepam_od.htm| title= Diazepam: overdose| work= Rxlist.com| publisher= RxList Inc.| access-date= 10 March 2006| archive-url= https://web.archive.org/web/20060216025309/http://www.rxlist.com/cgi/generic/diazepam_od.htm| archive-date= 16 February 2006| df= mdy-all}}</ref>
* Drowsiness
* Mental confusion
* [[Hypotension]]
* Impaired motor function
** Impaired reflexes
** Impaired coordination
** Impaired balance
** Dizziness
* [[Coma]]

Although not usually fatal when taken alone, a diazepam overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. The [[antidote]] for an overdose of diazepam (or any other benzodiazepine) is [[flumazenil]] (Anexate). This drug is used only in cases with severe respiratory depression or cardiovascular complications. Because flumazenil is a short-acting drug, and the effects of diazepam can last for days, several doses of flumazenil may be necessary. [[Artificial respiration]] and stabilization of cardiovascular functions may also be necessary. Though not routinely indicated, [[activated charcoal]] can be used for decontamination of the stomach following a diazepam overdose. [[Emesis]] is contraindicated. [[Kidney dialysis|Dialysis]] is minimally effective. Hypotension may be treated with [[levarterenol]] or [[metaraminol]].<ref name="Drugs.com" /><ref name="Inchem" /><ref name="RXL.Overdose" /><ref name="Barondes1" />

The oral {{LD50}} (lethal dose in 50% of the population) of diazepam is {{Val|720|u=mg/kg}} in mice and {{Val|1240|u=mg/kg}} in rats.<ref name="Drugs.com" /> D. J. Greenblatt and colleagues reported in 1978 on two patients who had taken {{Val|500|u=mg}} and {{Val|2000|u=mg}} of diazepam, respectively, went into moderately-deep comas, and were discharged within 48 hours without having experienced any important complications, despite having high concentrations of diazepam and its metabolites [[desmethyldiazepam]], oxazepam, and temazepam, according to samples taken in the hospital and as follow-up.<ref name="pmid357765">{{cite journal | vauthors = Greenblatt DJ, Woo E, Allen MD, Orsulak PJ, Shader RI | title = Rapid recovery from massive diazepam overdose | journal = JAMA | volume = 240 | issue = 17 | pages = 1872–4 | date = October 1978 | pmid = 357765 | doi = 10.1001/jama.1978.03290170054026 }}</ref>

Overdoses of diazepam with alcohol, opiates, or other depressants may be fatal.<ref name="Barondes1" /><ref name="pmid16879940">{{cite journal | vauthors = Lai SH, Yao YJ, Lo DS | title = A survey of buprenorphine related deaths in Singapore | journal = Forensic Science International | volume = 162 | issue = 1–3 | pages = 80–6 | date = October 2006 | pmid = 16879940 | doi = 10.1016/j.forsciint.2006.03.037 }}</ref>

==Interactions==
If diazepam is administered concomitantly with other drugs, it is recommended that attention be paid to the possible pharmacological interactions. Particular care is taken with drugs that potentiate the effects of diazepam, such as barbiturates, [[phenothiazine]]s, [[opioid]]s, and [[antidepressant]]s.<ref name="Drugs.com" />

Diazepam does not increase or decrease hepatic enzyme activity and does not alter the metabolism of other compounds. No evidence has suggested that diazepam alters its metabolism with chronic administration.<ref name="Inchem" />

Agents with an effect on hepatic [[cytochrome P450]] pathways or [[Conjugation (pharmacokinetics)|conjugation]] can alter the rate of diazepam metabolism. These interactions would be expected to be most significant with long-term diazepam therapy, and their clinical significance is variable.<ref name="Inchem" />
* Diazepam increases the central depressive effects of alcohol, other [[hypnotic]]s/sedatives (e.g., barbiturates), other [[muscle relaxant]]s, certain antidepressants, sedative [[antihistamine]]s, [[opioid]]s, and [[antipsychotic]]s, as well as [[anticonvulsant]]s such as [[phenobarbital]], [[phenytoin]], and [[carbamazepine]]. The euphoriant effects of opioids may be increased, leading to an increased risk of psychological dependence.<ref name="pmid18384456" /><ref name="PDRhealth">{{cite web| year= 2006| url= http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/val1473.shtml| title= Diazepam| work= PDRHealth.com| access-date= 10 March 2006 |archive-url = https://web.archive.org/web/20060117065720/http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/val1473.shtml <!-- Bot retrieved archive --> |archive-date = 17 January 2006}}</ref><ref name="Holt">{{cite book | vauthors = Holt GA | year= 1998| title= Food and Drug Interactions: A Guide for Consumers| pages= 90–91| location= Chicago | publisher=Precept Press| isbn= 978-0-944496-59-6 }}</ref>
* [[Cimetidine]], [[omeprazole]], [[oxcarbazepine]], [[ticlopidine]], [[topiramate]], [[ketoconazole]], [[itraconazole]], [[disulfiram]], [[fluvoxamine]], [[isoniazid]], [[erythromycin]], [[probenecid]], [[propranolol]], [[imipramine]], [[ciprofloxacin]], [[fluoxetine]], and [[valproic acid]] prolong the action of diazepam by inhibiting its elimination.<ref name="pmid18384456" /><ref name="Inchem" /><ref name="ElephantCare" />
* [[Ethanol|Alcohol]] in combination with diazepam may cause a [[synergistic]] enhancement of the hypotensive properties of benzodiazepines and alcohol.<ref name="pmid7163374">{{cite journal | vauthors = Zácková P, Kvĕtina J, Nĕmec J, Nĕmcová J | title = Cardiovascular effects of diazepam and nitrazepam in combination with ethanol | journal = Die Pharmazie | volume = 37 | issue = 12 | pages = 853–6 | date = December 1982 | pmid = 7163374 }}</ref>
* Oral contraceptives significantly decrease the elimination of [[desmethyldiazepam]], a major metabolite of diazepam.<ref name="PDRhealth" /><ref name="pmid2191822">{{cite journal | vauthors = Back DJ, Orme ML | s2cid = 32523973 | title = Pharmacokinetic drug interactions with oral contraceptives | journal = Clinical Pharmacokinetics | volume = 18 | issue = 6 | pages = 472–84 | date = June 1990 | pmid = 2191822 | doi = 10.2165/00003088-199018060-00004 }}</ref>
* Rifampin, phenytoin, carbamazepine, and phenobarbital increase the metabolism of diazepam, thus decreasing drug levels and effects.<ref name="Inchem" /> [[Dexamethasone]] and [[Hypericum perforatum|St John's wort]] also increase the metabolism of diazepam.<ref name="pmid18384456" />
* Diazepam increases the serum levels of phenobarbital.<ref name="pmid7374896">{{cite journal | vauthors = Bendarzewska-Nawrocka B, Pietruszewska E, Stepień L, Bidziński J, Bacia T | title = [Relationship between blood serum luminal and diphenylhydantoin level and the results of treatment and other clinical data in drug-resistant epilepsy] | journal = Neurologia I Neurochirurgia Polska | volume = 14 | issue = 1 | pages = 39–45 | date = January–February 1980 | pmid = 7374896 }}</ref>
* [[Nefazodone]] can cause increased blood levels of benzodiazepines.<ref name="PDRhealth" />
* [[Cisapride]] may enhance the absorption, and therefore the sedative activity, of diazepam.<ref name="pmid3709647">{{cite journal | vauthors = Bateman DN | s2cid = 41495586 | title = The action of cisapride on gastric emptying and the pharmacodynamics and pharmacokinetics of oral diazepam | journal = European Journal of Clinical Pharmacology | volume = 30 | issue = 2 | pages = 205–8 | year = 1986 | pmid = 3709647 | doi = 10.1007/BF00614304 }}</ref>
* Small doses of [[theophylline]] may inhibit the action of diazepam.<ref name="pmid6374311">{{cite journal | vauthors = Mattila MJ, Nuotto E | title = Caffeine and theophylline counteract diazepam effects in man | journal = Medical Biology | volume = 61 | issue = 6 | pages = 337–43 | year = 1983 | pmid = 6374311 }}</ref>
* Diazepam may block the action of [[levodopa]] (used in the treatment of [[Parkinson's disease]]).<ref name="Holt" />
* Diazepam may alter [[digoxin]] serum concentrations.<ref name="Inchem" />
* Other drugs that may have interactions with diazepam include [[antipsychotic]]s (e.g. [[chlorpromazine]]), [[MAO inhibitors]], and [[ranitidine]].<ref name="PDRhealth" />
* Because it acts on the GABA receptor, the herb [[Valerian (herb)|valerian]] may produce an adverse effect.<ref name="University of Maryland Medical Center-2013">{{cite web |title=Possible Interactions with: Valerian |work=[[University of Maryland Medical Center]] |url=http://www.umm.edu/altmed/articles/valerian-000934.htm |date=13 May 2013 |access-date=12 December 2014 |url-status=live |archive-url=https://web.archive.org/web/20130121185201/http://www.umm.edu/altmed/articles/valerian-000934.htm |archive-date=21 January 2013 }}</ref>
* Foods that acidify the urine can lead to faster absorption and elimination of diazepam, reducing drug levels and activity.<ref name="Holt" />
* Foods that alkalinize the urine can lead to slower absorption and elimination of diazepam, increasing drug levels and activity.<ref name="Inchem" />
* Reports conflict as to whether food in general has any effects on the absorption and activity of orally administered diazepam.<ref name="Holt" />

==Pharmacology==
[[File:5mgrocheaus.jpg|thumb|{{Val|5|u=mg}} Valium Roche packaging Australia]]
Diazepam is a long-acting "classical" benzodiazepine. Other classical benzodiazepines include [[chlordiazepoxide]], [[clonazepam]], [[lorazepam]], [[oxazepam]], [[nitrazepam]], [[temazepam]], [[flurazepam]], [[bromazepam]], and [[clorazepate]].<ref name="pmid639854">{{cite journal | vauthors = Braestrup C, Squires RF | title = Pharmacological characterization of benzodiazepine receptors in the brain | journal = European Journal of Pharmacology | volume = 48 | issue = 3 | pages = 263–70 | date = April 1978 | pmid = 639854 | doi = 10.1016/0014-2999(78)90085-7 }}</ref> Diazepam has [[anticonvulsant]] properties.<ref name="pmid2983169">{{cite journal | vauthors = Chweh AY, Swinyard EA, Wolf HH, Kupferberg HJ | title = Effect of GABA agonists on the neurotoxicity and anticonvulsant activity of benzodiazepines | journal = Life Sciences | volume = 36 | issue = 8 | pages = 737–44 | date = February 1985 | pmid = 2983169 | doi = 10.1016/0024-3205(85)90193-6 }}</ref> Benzodiazepines act via [[micromolar]] benzodiazepine binding sites as [[calcium channel blocker]]s and significantly inhibit depolarization-sensitive [[calcium]] uptake in rat nerve cell preparations.<ref name="pmid6328498">{{cite journal | vauthors = Taft WC, DeLorenzo RJ | title = Micromolar-affinity benzodiazepine receptors regulate voltage-sensitive calcium channels in nerve terminal preparations | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 10 | pages = 3118–22 | date = May 1984 | pmid = 6328498 | pmc = 345232 | doi = 10.1073/pnas.81.10.3118 | url = http://www.pnas.org/cgi/reprint/81/10/3118.pdf | url-status = live | type = PDF | archive-url = https://web.archive.org/web/20080625212037/http://www.pnas.org/cgi/reprint/81/10/3118.pdf | archive-date = 25 June 2008 | bibcode = 1984PNAS...81.3118T | doi-access = free }}</ref>

Diazepam inhibits [[acetylcholine]] release in mouse hippocampal [[synaptosome]]s. This has been found by measuring sodium-dependent high-affinity choline uptake in [[mouse brain]] cells ''in vitro'', after pretreatment of the mice with diazepam ''in vivo''. This may play a role in explaining diazepam's anticonvulsant properties.<ref name="pmid3978310">{{cite journal | vauthors = Miller JA, Richter JA | title = Effects of anticonvulsants in vivo on high affinity choline uptake in vitro in mouse hippocampal synaptosomes | journal = British Journal of Pharmacology | volume = 84 | issue = 1 | pages = 19–25 | date = January 1985 | pmid = 3978310 | pmc = 1987204 | doi = 10.1111/j.1476-5381.1985.tb17368.x }}</ref>

Diazepam binds with high affinity to [[glial cells]] in animal cell cultures.<ref name="pmid6267221">{{cite journal | vauthors = Gallager DW, Mallorga P, Oertel W, Henneberry R, Tallman J | title = [3H]Diazepam binding in mammalian central nervous system: a pharmacological characterization | journal = The Journal of Neuroscience | volume = 1 | issue = 2 | pages = 218–25 | date = February 1981 | pmid = 6267221 | pmc = 6564145 | doi = 10.1523/JNEUROSCI.01-02-00218.1981 }}</ref> Diazepam at high doses has been found to decrease [[histamine]] turnover in mouse brain via diazepam's action at the benzodiazepine-GABA receptor complex.<ref name="pmid3089825">{{cite journal | vauthors = Oishi R, Nishibori M, Itoh Y, Saeki K | title = Diazepam-induced decrease in histamine turnover in mouse brain | journal = European Journal of Pharmacology | volume = 124 | issue = 3 | pages = 337–42 | date = May 1986 | pmid = 3089825 | doi = 10.1016/0014-2999(86)90236-0 }}</ref> Diazepam also decreases [[prolactin]] release in rats.<ref name="pmid6979001">{{cite journal | vauthors = Grandison L | title = Suppression of prolactin secretion by benzodiazepines in vivo | journal = Neuroendocrinology | volume = 34 | issue = 5 | pages = 369–73 | year = 1982 | pmid = 6979001 | doi = 10.1159/000123330 }}</ref>

===Mechanism of action===
{{See also|Benzodiazepine}}

Benzodiazepines are [[positive allosteric modulators]] of the GABA type A receptors ([[GABAA|GABA<sub>A</sub>]]). The GABA<sub>A</sub> receptors are [[Ligand-gated ion channel|ligand-gated chloride-selective ion channels]] that are activated by [[GABA]], the major [[inhibitory neurotransmitter]] in the brain. The binding of benzodiazepines to this receptor complex promotes the binding of GABA, which in turn increases the total conduction of chloride ions across the neuronal cell membrane. This increased chloride ion influx [[Hyperpolarization (biology)|hyperpolarizes]] the neuron's [[membrane potential]]. As a result, the difference between [[resting potential]] and [[threshold potential]] is increased, and firing is less likely. As a result, the arousal of the [[Cerebral cortex|cortical]] and [[limbic system]]s in the central nervous system is reduced.<ref name="auto">{{cite web |url=https://one.nhtsa.gov/people/injury/research/job185drugs/diazepam.htm |title=National Highway Traffic Safety Administration Drugs and Human Performance Fact Sheet- Diazepam |access-date=13 November 2017 |archive-url=https://web.archive.org/web/20170327233605/https://one.nhtsa.gov/people/INJURY/research/job185drugs/diazepam.htm |archive-date=27 March 2017 }}</ref>

The GABA<sub>A</sub> receptor is a [[heteromer]] composed of five subunits, the most common ones being two αs, two βs, and one γ (α2β2γ). For each subunit, many subtypes exist (α1–6, β1–3, and γ1–3). GABA<sub>A</sub> receptors containing the α1 subunit mediate the sedative, anterograde amnesic, and partly the anticonvulsive effects of diazepam. GABA<sub>A</sub> receptors containing α2 mediate the anxiolytic actions and, to a large degree, the myorelaxant effects. GABA<sub>A</sub> receptors containing α3 and α5 also contribute to benzodiazepines myorelaxant actions, whereas GABA<sub>A</sub> receptors comprising the α5 subunit were shown to modulate the temporal and spatial memory effects of benzodiazepines.<ref name="Tan-2011">{{cite web | vauthors = Tan KR, Rudolph U, Lüscher C |title=Hooked on benzodiazepines: GABA<sub>A</sub> receptor subtypes and addiction |url=http://www.addictionscience.unige.ch/LabPublications-1/TrendsNeurosciKT2011.pdf |work=[[University of Geneva]] |date=2011 |access-date=12 December 2014 |url-status=live |archive-url=https://web.archive.org/web/20150701230113/http://www.addictionscience.unige.ch/LabPublications-1/TrendsNeurosciKT2011.pdf |archive-date=1 July 2015 }}</ref> Diazepam is not the only drug to target these GABA<sub>A</sub> receptors. Drugs such as [[flumazenil]] also bind to GABA<sub>A</sub> to induce their effects.<ref name="pmid22992668">{{cite journal | vauthors = Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, Altman RB, Klein TE | title = Pharmacogenomics knowledge for personalized medicine | journal = Clinical Pharmacology and Therapeutics | volume = 92 | issue = 4 | pages = 414–7 | date = October 2012 | pmid = 22992668 | pmc = 3660037 | doi = 10.1038/clpt.2012.96 }}</ref>

Diazepam appears to act on areas of the [[limbic system]], [[thalamus]], and [[hypothalamus]], inducing anxiolytic effects. Benzodiazepine drugs, including diazepam, increase the inhibitory processes in the [[cerebral cortex]].<ref name="pmid23084">{{cite journal | vauthors = Zakusov VV, Ostrovskaya RU, Kozhechkin SN, Markovich VV, Molodavkin GM, Voronina TA | title = Further evidence for GABA-ergic mechanisms in the action of benzodiazepines | journal = Archives Internationales de Pharmacodynamie et de Thérapie | volume = 229 | issue = 2 | pages = 313–26 | date = October 1977 | pmid = 23084 }}</ref>

The anticonvulsant properties of diazepam and other benzodiazepines may be in part or entirely due to binding to [[voltage-dependent sodium channels]] rather than GABA<sub>A</sub> receptors. Sustained repetitive firing seems limited by benzodiazepines' effect of slowing recovery of sodium channels from inactivation.<ref name="pmid2450203">{{cite journal | vauthors = McLean MJ, Macdonald RL | title = Benzodiazepines, but not beta-carbolines, limit high-frequency repetitive firing of action potentials of spinal cord neurons in cell culture | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 244 | issue = 2 | pages = 789–95 | date = February 1988 | doi = 10.1016/S0022-3565(25)24414-7 | pmid = 2450203 }}</ref>

The muscle relaxant properties of diazepam are produced via inhibition of [[polysynaptic]] pathways in the spinal cord.<ref name="pmid6517646">{{cite journal | vauthors = Date SK, Hemavathi KG, Gulati OD | title = Investigation of the muscle relaxant activity of nitrazepam | journal = Archives Internationales de Pharmacodynamie et de Thérapie | volume = 272 | issue = 1 | pages = 129–39 | date = November 1984 | pmid = 6517646 }}</ref>

===Pharmacokinetics===
Diazepam can be administered orally, intravenously (it is always diluted, as it is painful and damaging to veins), [[intramuscular injection|intramuscularly]] (IM), or as a [[suppository]].<ref name="Inchem">{{cite web | vauthors = Munne P | veditors = Ruse M | year= 1998 | url= http://www.inchem.org/documents/pims/pharm/pim181.htm | title= Diazepam | work= Inchem.org | access-date= 11 March 2006 | url-status=live | archive-url= https://web.archive.org/web/20060227195320/http://www.inchem.org/documents/pims/pharm/pim181.htm | archive-date= 27 February 2006 }}</ref>

The onset of action is one to five minutes for IV administration and 15–30 minutes for IM administration. The duration of diazepam's peak pharmacological effects is 15 minutes to one hour for both routes of administration.<ref name="Cuny.edu">{{cite web | vauthors = Langsam Y | url= http://eilat.sci.brooklyn.cuny.edu/newnyc/DRUGS/Diazepam.htm | title= Diazepam (Valium and Others) | publisher= Brooklyn College (Eilat.sci.Brooklyn.CUNY.edu) | access-date= 23 March 2006 | url-status=live | archive-url= https://web.archive.org/web/20070730114031/http://eilat.sci.brooklyn.cuny.edu/newnyc/DRUGS/Diazepam.htm | archive-date= 30 July 2007 }}</ref> The half-life of diazepam, in general, is 30–56 hours.<ref name="auto"/> Peak plasma levels occur between 30 and 90 minutes after oral administration and between 30 and 60 minutes after intramuscular administration; after rectal administration, peak plasma levels occur after 10 to 45 minutes. Diazepam is highly [[Protein bound|plasma protein-bound]], with 96–99% of the absorbed drug being protein-bound. The distribution half-life of diazepam is two to 13 minutes.<ref name="pmid18384456" />

Diazepam is highly lipid-soluble and is widely distributed throughout the body after administration. It easily crosses both the [[blood–brain barrier]] and the [[placenta]], and is excreted into breast milk. After absorption, diazepam is redistributed into [[muscle]] and [[adipose]] tissue. Continual daily doses of diazepam quickly build to a high concentration in the body (mainly in [[adipose tissue]]), far above the actual dose for any given day.<ref name="pmid18384456" /><ref name="Inchem" />

Diazepam is stored preferentially in some organs, including the heart. Absorption by any administered route and the risk of accumulation is significantly increased in the [[neonate]], and withdrawal of diazepam during pregnancy and breastfeeding is clinically justified.<ref name="pmid851373">{{cite journal | vauthors = Olive G, Dreux C | title = [Pharmacologic bases of use of benzodiazepines in peréinatal medicine] | journal = Archives Françaises de Pédiatrie | volume = 34 | issue = 1 | pages = 74–89 | date = January 1977 | pmid = 851373 }}</ref>

Diazepam undergoes [[oxidative metabolism]] by [[demethylation]] ([[CYP2C9]], [[CYP2C19|2C19]], [[CYP2B6|2B6]], [[CYP3A4|3A4]], and [[CYP3A5|3A5]]), [[hydroxylation]] (CYP3A4 and 2C19) and [[glucuronidation]] in the liver as part of the [[cytochrome P450]] enzyme system. It has several pharmacologically [[active metabolite]]s. The main active metabolite of diazepam is [[nordiazepam|desmethyldiazepam]] (also known as nordazepam or nordiazepam). Its other active metabolites include the minor active metabolites [[temazepam]] and [[oxazepam]]. These metabolites are conjugated with [[glucuronide]] and are excreted primarily in the urine. Because of these active metabolites, the serum values of diazepam alone are not useful in predicting the effects of the drug. Diazepam has a biphasic half-life of about one to three days and two to seven days for the active metabolite desmethyldiazepam.<ref name="pmid18384456" /> Most of the drug is metabolized; very little diazepam is excreted unchanged.<ref name="Inchem" /> The elimination half-life of diazepam and also the active metabolite desmethyldiazepam increases significantly in the elderly, which may result in prolonged action, as well as accumulation of the drug during repeated administration.<ref name="pmid6118950">{{cite journal | vauthors = Vozeh S | title = [Pharmacokinetic of benzodiazepines in old age] | journal = Schweizerische Medizinische Wochenschrift | volume = 111 | issue = 47 | pages = 1789–93 | date = November 1981 | pmid = 6118950 }}</ref>

=== Synthesis ===
The synthesis of Diazepam was first achieved through a reaction pathway developed by Leo Sternbach and his team at Hoffmann-La Roche in the late 1950s.

Sternbach's method commenced with [[2-amino-5-chlorobenzophenone]], which undergoes cyclocondensation with glycine ethyl ester hydrochloride to construct the benzodiazepine core. This core is subsequently alkylated at the nitrogen in the 1-position using [[dimethyl sulfate]] in the presence of [[sodium methoxide]] and [[methanol]] under reflux conditions. Although the direct transformation from 2-amino-5-chlorobenzophenone to Nordazepam is conceptually straightforward, an alternative approach involving the treatment of 2-amino-5-chlorobenzophenon with [[chloroacetyl chloride]], succeeded by ammoniation and heating, culminates in Nordazepam with enhanced yield and facilitates easier purification processes.<ref>{{cite journal | vauthors = Stempel A, Reeder E, Sternbach LH | title = Quinazolines and 1,4-benzodiazepines. XXVII. Mechanism of ring enlargement of quinazoline 3-oxides with alkali to 1,4-benzodiazepin-2-one 4-oxides | journal = The Journal of Organic Chemistry | volume = 30 | issue = 12 | pages = 4267–4271 | date = December 1965 | pmid = 4158669 | doi = 10.1021/jo01023a063 }}</ref>
[[File:Synthesis of Diazepam.jpg|class=skin-invert-image|center|653x653px]]

===Detection in body fluids===
Diazepam may be quantified in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an impaired driving arrest, or assist in a medicolegal death investigation. Blood or plasma diazepam concentrations are usually in a range of {{Val|0.1|-|1.0|u=mg/L}} in persons receiving the drug therapeutically. Most commercial [[immunoassay]]s for the benzodiazepine class of drugs cross-react with diazepam, but confirmation and quantitation are usually performed using [[Chromatography|chromatographic]] techniques.<ref name="pmid17417081">{{cite journal | vauthors = Jones AW, Holmgren A, Kugelberg FC | s2cid = 25511804 | title = Concentrations of scheduled prescription drugs in blood of impaired drivers: considerations for interpreting the results | journal = Therapeutic Drug Monitoring | volume = 29 | issue = 2 | pages = 248–60 | date = April 2007 | pmid = 17417081 | doi = 10.1097/FTD.0b013e31803d3c04 }}</ref><ref name="pmid1675703">{{cite journal | vauthors = Fraser AD, Bryan W | title = Evaluation of the Abbott ADx and TDx serum benzodiazepine immunoassays for analysis of alprazolam | journal = Journal of Analytical Toxicology | volume = 15 | issue = 2 | pages = 63–5 | year = 1991 | pmid = 1675703 | doi = 10.1093/jat/15.2.63 }}</ref><ref name="Baselt-2011">{{cite book | vauthors = Baselt R |title=Disposition of Toxic Drugs and Chemicals in Man |edition=9th |publisher=Biomedical Publications |location=Seal Beach, CA |year=2011 |pages=471–473 |isbn=978-0-9626523-8-7}}</ref>

===Environmental===
Diazepam is a common [[environmental contamination]] finding near human settlements.<ref name="pmid33780670">{{cite journal | vauthors = Chia MA, Lorenzi AS, Ameh I, Dauda S, Cordeiro-Araújo MK, Agee JT, Okpanachi IY, Adesalu AT | title = Susceptibility of phytoplankton to the increasing presence of active pharmaceutical ingredients (APIs) in the aquatic environment: A review | journal = Aquatic Toxicology | volume = 234 | article-number = 105809 | date = May 2021 | pmid = 33780670 | doi = 10.1016/j.aquatox.2021.105809 | bibcode = 2021AqTox.23405809C | s2cid = 232419482 }}</ref>

== Chemistry ==
Diazepam does not possess any [[Chirality (chemistry)|chiral]] centers in its structure, but it does have two [[Conformational isomerism|conformers]]: the 'P'-conformer and 'M'-conformer. Diazepam is an equimolar mixture, and it was shown through CD spectra in serum protein solutions that the 'P'-conformer is preferred by α1-acid glycoprotein binding.{{Citation needed|date=October 2025}}

The drug diazepam occurs as a pale yellow-white crystalline powder without a distinctive smell and has a low molecular weight (MW = 284.74 g/mol<ref name="PubChem" />). This classic aryl 1,4-benzodiazepine possesses three acceptors and no hydrogen bond donors. Diazepam is moderately lipophilic with LogP (Octanol-Water Partition Coefficient) value of 2,82 and hydrophilic with a TPSA (Topological Polar Surface Area) value of 32.7 Å².<ref name="PubChem" /> The LogP value indicates that diazepam tends to dissolve more readily in lipid-based environments, such as chloroform, acetone, ethanol and ether, compared to water. The TPSA value implies that a segment of the molecule exhibits a degree of polarity or hydrophilicity and represents the collective surface area of polar atoms, like oxygen or nitrogen, along with their connected hydrogen atoms. A TPSA value of 32,7 Å² signifies a moderate level of polarity within the compound. TPSA is especially useful in medical chemistry as it shows the ability of a molecule to permeate cells. Molecules with a PSA value smaller than 60–70 Å² have a better ability to permeate cells.<ref>{{cite journal |vauthors=Pajouhesh H, Lenz GR |date=October 2005 |title=Medicinal chemical properties of successful central nervous system drugs |journal=NeuroRx |volume=2 |issue=4 |pages=541–553 |doi=10.1602/neurorx.2.4.541 |pmc=1201314 |pmid=16489364}}</ref> The balance between its lipophilic and hydrophilic characteristics can impact various aspects of the molecule's behavior, including its solubility, absorption, distribution, metabolism, and potential interactions within the biological system.{{Citation needed|date=October 2025}}

Diazepam is overall a stable molecule. The [[British Pharmacopoeia]] lists it as being very slightly soluble in water, soluble in alcohol, and freely soluble in chloroform. The [[United States Pharmacopoeia]] lists diazepam as soluble 1 in 16 ethyl alcohol, 1 in 2 of chloroform, 1 in 39 [[diethyl ether|ether]], and practically insoluble in water. The [[pH]] of diazepam is neutral (i.e., pH = 7).<ref name="Plumbs372">Plumb's, 6th edition page 372</ref> Diazepam has a shelf life of five years for oral tablets and three years for IV/IM solutions.<ref name="Inchem" />Diazepam is stored at room temperature (15–30&nbsp;°C). The solution for parenteral injection is kept so that it is protected from light and kept from freezing. The oral forms are stored in air-tight containers and protected from light.<ref name="ElephantCare" />

Diazepam can be absorbed into plastics, so liquid preparations are not kept in plastic bottles or syringes, etc. As such, it can leach into the plastic bags and tubing used for intravenous infusions. Absorption appears to depend on several factors, such as temperature, concentration, flow rates, and tube length. Diazepam should not be administered if a precipitate has formed and does not dissolve.<ref name="ElephantCare" />

==History==
Diazepam was the second benzodiazepine invented by [[Leo Sternbach]] of [[Hoffmann-La Roche]] at the company's [[Nutley, New Jersey]], facility<ref name="Pollack-2012">{{cite news |url=https://www.nytimes.com/2012/06/27/business/roche-to-shut-down-former-us-headquarters-after-83-years.html |title=Roche to Shut Former U.S. Headquarters |newspaper=New York Times | vauthors = Pollack A |date=26 June 2012 |access-date=10 January 2014 |url-status=live |archive-url=https://web.archive.org/web/20130331200545/http://www.nytimes.com/2012/06/27/business/roche-to-shut-down-former-us-headquarters-after-83-years.html |archive-date=31 March 2013 }}</ref> following [[chlordiazepoxide]] (Librium), which was approved for use in 1960. Released in 1963 as an improved version of Librium, diazepam became incredibly popular, helping Roche to become a pharmaceutical industry giant. It is 2.5 times more potent than its predecessor, which it quickly surpassed in terms of sales. After this initial success, other pharmaceutical companies began to introduce other benzodiazepine derivatives.<ref name="Sample-2005">{{cite news| vauthors= Sample I| title= Leo Sternbach's Obituary| date= 3 October 2005| publisher= The Guardian (Guardian Unlimited)| url= https://www.theguardian.com/medicine/story/0,,1583671,00.html| access-date= 10 March 2006| archive-date= 28 August 2021| archive-url= https://web.archive.org/web/20210828061851/https://www.theguardian.com/society/2005/oct/03/health.guardianobituaries| url-status= live}}</ref>

The benzodiazepines gained popularity among medical professionals as an improvement over [[barbiturate]]s, which have a comparatively narrow [[therapeutic index]], and are far more sedative at therapeutic doses. The benzodiazepines are also far less dangerous; death rarely results from diazepam overdose, except in cases where it is consumed with large amounts of other [[depressant]]s (such as alcohol or opioids).<ref name="Barondes1">{{cite book | vauthors = Barondes SH | year= 2003 | title= Better Than Prozac | pages= [https://archive.org/details/betterthanprozac00baro/page/47 47–59] | location= New York | publisher= Oxford University Press | isbn= 978-0-19-515130-5 | url-access= registration | url= https://archive.org/details/betterthanprozac00baro/page/47 }}</ref> Benzodiazepine drugs such as diazepam initially had widespread public support, but with time the view changed to one of growing criticism and calls for restrictions on their prescription.<ref name="pmid19524858">{{cite journal | vauthors = Marshall KP, Georgievskava Z, Georgievsky I | title = Social reactions to Valium and Prozac: a cultural lag perspective of drug diffusion and adoption | journal = Research in Social & Administrative Pharmacy | volume = 5 | issue = 2 | pages = 94–107 | date = June 2009 | pmid = 19524858 | doi = 10.1016/j.sapharm.2008.06.005 }}</ref>

Marketed by Roche using an advertising campaign conceived by the William Douglas McAdams Agency under the leadership of [[Arthur Sackler]],<ref name="Theweek.com-2015">{{cite web|url=https://theweek.com/articles/541564/how-american-opiate-epidemic-started-by-pharmaceutical-company|title=How the American opiate epidemic was started by one pharmaceutical company|date=4 March 2015|website=Theweek.com|access-date=10 January 2018|archive-date=10 January 2018|archive-url=https://web.archive.org/web/20180110022307/http://theweek.com/articles/541564/how-american-opiate-epidemic-started-by-pharmaceutical-company|url-status=live}}</ref> diazepam was the top-selling pharmaceutical in the United States from 1969 to 1982, with peak annual sales in 1978 of 2.3&nbsp;billion tablets.<ref name="Sample-2005" /> Diazepam, along with [[oxazepam]], [[nitrazepam]] and [[temazepam]], represents 82% of the benzodiazepine market in Australia.<ref name="pmid7911332">{{cite journal | vauthors = Mant A, Whicker SD, McManus P, Birkett DJ, Edmonds D, Dumbrell D | title = Benzodiazepine utilisation in Australia: report from a new pharmacoepidemiological database | journal = Australian Journal of Public Health | volume = 17 | issue = 4 | pages = 345–9 | date = December 1993 | pmid = 7911332 | doi = 10.1111/j.1753-6405.1993.tb00167.x | doi-access = free }}</ref> While psychiatrists continue to prescribe diazepam for the short-term relief of anxiety, neurology has taken the lead in prescribing diazepam for the [[palliative]] treatment of certain types of epilepsy and spastic activity, for example, forms of [[paresis]].{{Citation needed|date=January 2023}} It is also the first line of defense for a rare disorder called [[stiff-person syndrome]].<ref name="RXL.Indications">{{cite web | date= 24 January 2005 | url= http://www.rxlist.com/cgi/generic/diazepam_ids.htm | title= Diazepam: indications | work= Rxlist.com | publisher= RxList Inc. | access-date= 11 March 2006 | archive-url= https://web.archive.org/web/20060216025337/http://www.rxlist.com/cgi/generic/diazepam_ids.htm | archive-date= 16 February 2006 | df= mdy-all }}</ref>

==Society and culture==
===Recreational use===
{{See also|Benzodiazepine drug misuse}}
Diazepam is a medication with a high risk of misuse and can cause [[drug dependence]]. Some pharmacologists recommend urgent action by national governments to improve prescribing patterns of benzodiazepines such as diazepam.<ref name="pmid15926867">{{cite journal | vauthors = Atack JR | title = The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics | journal = Expert Opinion on Investigational Drugs | volume = 14 | issue = 5 | pages = 601–18 | date = May 2005 | pmid = 15926867 | doi = 10.1517/13543784.14.5.601 | s2cid = 22793644 }}</ref><ref name="pmid16671957">{{cite journal | vauthors = Dièye AM, Sylla M, Ndiaye A, Ndiaye M, Sy GY, Faye B | title = Benzodiazepines prescription in Dakar: a study about prescribing habits and knowledge in general practitioners, neurologists and psychiatrists | journal = Fundamental & Clinical Pharmacology | volume = 20 | issue = 3 | pages = 235–8 | date = June 2006 | pmid = 16671957 | doi = 10.1111/j.1472-8206.2006.00400.x | s2cid = 20619323 }}</ref> A single dose of diazepam modulates the [[dopamine]] system in similar ways to how morphine and [[ethanol|alcohol]] modulate the dopaminergic pathways.<ref name="Medical News Today-2008">{{cite news |url=http://www.medicalnewstoday.com/articles/119284.php |title=New Evidence on Addiction To Medicines Diazepam Has Effect on Nerve Cells in the Brain Reward System |access-date=25 September 2008 |date=August 2008 |work=Medical News Today |url-status=live |archive-url=https://web.archive.org/web/20080912163645/http://www.medicalnewstoday.com/articles/119284.php |archive-date=12 September 2008 }}</ref>
Between 50 and 64% of rats will self-administer diazepam.<ref name="pmid6538866">{{cite journal | vauthors = Yoshimura K, Horiuchi M, Inoue Y, Yamamoto K | title = [Pharmacological studies on drug dependence. (III): Intravenous self-administration of some CNS-affecting drugs and a new sleep-inducer, 1H-1, 2, 4-triazolyl benzophenone derivative (450191-S), in rats] | journal = Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica | volume = 83 | issue = 1 | pages = 39–67 | date = January 1984 | pmid = 6538866 | doi = 10.1254/fpj.83.39 | doi-access = free }}</ref>
Diazepam can substitute for the behavioral effects of [[barbiturate]]s in a [[primate]] study.<ref name="pmid8748392">{{cite journal | vauthors = Woolverton WL, Nader MA | s2cid = 24836734 | title = Effects of several benzodiazepines, alone and in combination with flumazenil, in rhesus monkeys trained to discriminate pentobarbital from saline | journal = Psychopharmacology | volume = 122 | issue = 3 | pages = 230–6 | date = December 1995 | pmid = 8748392 | doi = 10.1007/BF02246544 }}</ref>
Diazepam has been found as an [[adulterant]] in [[heroin]].<ref name=heroin_adulterant>{{cite web |url=http://www.incb.org/documents/Publications/AnnualReports/AR1996/AR_1996_E.pdf#37 |format=PDF |access-date=12 December 2014 |publisher=International Narcotics Control Board |work=United Nations |title=Report of the International Narcotics Control Board for 1996 |year=1996 |page=27 |quote=Phenobarbital was identified as the psychotropic substance most frequently used as an adulterant in seized heroin; it was followed by diazepam and flunitrazepam. |url-status=live |archive-url=https://web.archive.org/web/20150924034301/http://www.incb.org/documents/Publications/AnnualReports/AR1996/AR_1996_E.pdf#37 |archive-date=24 September 2015 }}</ref>

Diazepam drug misuse can occur either through [[Recreational drug use|recreational misuse]], where the drug is taken to achieve a high, or when the drug is continued long term against medical advice.<ref name="pmid16336040">{{cite journal | vauthors = Griffiths RR, Johnson MW | title = Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds | journal = The Journal of Clinical Psychiatry | volume = 66 | issue = Suppl 9 | pages = 31–41 | year = 2005 | pmid = 16336040 }}</ref>

Sometimes, it is used by [[stimulant]] users to "come down" and sleep and to help control the urge to binge. These users often escalate dosage from 2 to 25 times the therapeutic dose of {{Val|5|u=mg}} to {{Val|10|u=mg}}.<ref name="Erowid Experience Vaults">{{cite web |url=http://de1.erowid.org/experiences/exp.phpquery=ID=9402.html |title=Methamphetamine and Benzodiazepines: Methamphetamine & Benzodiazepines |access-date=26 September 2006 |vauthors=Overclocker |work=Erowid Experience Vaults |archive-date=18 December 2008 |archive-url=https://web.archive.org/web/20081218232840/http://de1.erowid.org/experiences/exp.phpquery=ID=9402.html }}</ref>

A large-scale study in the US, conducted by [[SAMHSA]], using data from 2011, determined that benzodiazepines were present in 28.7% of emergency department visits involving nonmedical use of pharmaceuticals. In this regard, benzodiazepines are second only to [[opiate]]s, the study found in 39.2% of visits. About 29.3% of [[drug-related suicide]] attempts involve benzodiazepines, making them the most frequently represented class in drug-related [[Suicide in the United States|suicide]] attempts. Males misuse benzodiazepines as commonly as females.<ref name="U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration-2011">{{cite web |url=http://www.samhsa.gov/data/2k13/DAWN2k11ED/DAWN2k11ED.htm#6.1 |title=Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits |access-date=20 April 2014 |publisher=U.S. Department of Health and Human Services, Substance Abuse and Mental Health Services Administration |author-link=Substance Abuse and Mental Health Services Administration |year=2011 |archive-url=https://web.archive.org/web/20140531024002/http://www.samhsa.gov/data/2k13/DAWN2k11ED/DAWN2k11ED.htm#6.1 |archive-date=31 May 2014 }}</ref>

Diazepam was detected in 26% of cases of people suspected of [[driving under the influence]] of drugs in Sweden, and its active metabolite nordazepam, was detected in 28% of cases. Other benzodiazepines, zolpidem, and zopiclone were also found in high numbers. Many drivers had blood levels far exceeding the therapeutic dose range, suggesting a high degree of potential for misuse of benzodiazepines, [[zolpidem]], and [[zopiclone]].<ref name="pmid17417081"/> In [[Northern Ireland]], in cases where drugs were detected in samples from impaired drivers who were not impaired by alcohol, benzodiazepines were found in 87% of cases. Diazepam was the most commonly detected benzodiazepine.<ref name="pmid3804143">{{cite journal | vauthors = Cosbey SH | title = Drugs and the impaired driver in Northern Ireland: an analytical survey | journal = Forensic Science International | volume = 32 | issue = 4 | pages = 245–58 | date = December 1986 | pmid = 3804143 | doi = 10.1016/0379-0738(86)90201-X }}</ref>

===Legal status===
Diazepam is regulated as a [[prescription medication]].

====International====
Diazepam is a Schedule IV controlled drug under the [[Convention on Psychotropic Substances]].<ref name="Legal">{{cite web| publisher=International Narcotics Control Board| year=2003| url=http://infoespai.org/wp-content/uploads/2014/12/green.pdf| title=List of psychotropic substances under international control| work=Green list| access-date=12 December 2014| archive-url=https://web.archive.org/web/20141213032231/http://infoespai.org/wp-content/uploads/2014/12/green.pdf| archive-date=13 December 2014}}</ref>

====UK====
Classified as a controlled drug, listed under Schedule IV, Part I (CD Benz POM) of the Misuse of Drugs Regulations 2001, allowing possession with a valid prescription. The [[Misuse of Drugs Act 1971]] makes it illegal to possess the drug without a prescription, and for such purposes, it is classified as a Class C drug.<ref name="List of controlled Drugs">{{cite web | url= http://www.homeoffice.gov.uk/publications/alcohol-drugs/drugs/drug-licences/controlled-drugs-list?view=Binary | title= List of controlled Drugs | url-status=live | archive-url= https://web.archive.org/web/20111230153451/http://www.homeoffice.gov.uk/publications/alcohol-drugs/drugs/drug-licences/controlled-drugs-list?view=Binary | archive-date= 30 December 2011 }}</ref>

====Germany====
Classified as a prescription drug, or in high dosage as a restricted drug (''Betäubungsmittelgesetz, Anlage III'').<ref name="Betäubungsmittelgesetz-2001">{{cite web| year=2001| url=http://bundesrecht.juris.de/btmg_1981/anlage_iii_61.html| title=Anlage III (zu §&nbsp;1 Abs.&nbsp;1) verkehrsfähige und verschreibungsfähige Betäubungsmittel| work=Betäubungsmittelgesetz| access-date=5 January 2010| archive-url=https://web.archive.org/web/20100103074308/http://bundesrecht.juris.de/btmg_1981/anlage_iii_61.html| archive-date=3 January 2010}}</ref>

====Australia====
Diazepam is a Schedule 4 substance under the [[Standard for the Uniform Scheduling of Medicines and Poisons|Poisons Standard]] (June 2018).<ref name="Poisons Standard">Poisons Standard June 2018 {{cite web |url=https://www.legislation.gov.au/Details/F2018L00625 |title=Poisons Standard June 2018 |access-date=6 January 2016 |url-status=live |archive-url=https://web.archive.org/web/20160119074606/https://www.comlaw.gov.au/Details/F2015L01534/ |archive-date=19 January 2016 }}</ref> A Schedule 4 drug is outlined in the [[Poisons Act 1964]] as, "Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription".<ref name="Poisons Standard" />

====United States====
Diazepam is controlled as a Schedule IV substance.<ref name="Valium FDA label" />

The states of [[California]] and [[Florida]] offer diazepam to [[Capital punishment|condemned]] inmates as a pre-execution sedative as part of their [[lethal injection]] program. The state of California has not executed a prisoner since 2006.<ref name="www.cdcr.ca.gov">{{cite web | url = http://www.cdcr.ca.gov/News/docs/RevisedProtocol.pdf | title = San Quentin State Prison Operational Procedure 0–770, Execution By Lethal Injection (pp. 44 & 92 | archive-url = https://web.archive.org/web/20080625212037/http://www.cdcr.ca.gov/News/docs/RevisedProtocol.pdf | archive-date=25 June 2008 | access-date = 10 January 2014 }}</ref><ref name=floridaDoc>{{cite web|title=Execution by lethal injection procedures|url=http://www.dc.state.fl.us/oth/deathrow/lethal-injection-procedures-as-of_9-9-2013.pdf|publisher=Florida Department of Corrections|access-date=25 August 2014|date=9 September 2013|url-status=live|archive-url=https://web.archive.org/web/20131108160534/http://www.dc.state.fl.us/oth/deathrow/lethal-injection-procedures-as-of_9-9-2013.pdf|archive-date=8 November 2013}}</ref> In August 2018, [[Nebraska]] used diazepam as part of the drug combination used to [[Execution of Carey Dean Moore|execute Carey Dean Moore]], the first death row inmate executed in Nebraska in over 21 years.<ref name="Lincoln Journal Star-2018">{{cite news | url = https://journalstar.com/news/local/911/nebraska-executes-carey-dean-moore-for-murders-of-omaha-cab/article_c2332b24-145e-51b8-9bd3-d4b13e64b70c.html#1 | title = Nebraska executes Carey Dean Moore for murders of Omaha cab drivers Maynard Helgeland, Reuel Van Ness Jr. | newspaper = Lincoln Journal Star | date = 14 August 2018 | access-date = 15 August 2018 | archive-date = 15 August 2018 | archive-url = https://web.archive.org/web/20180815024214/https://journalstar.com/news/local/911/nebraska-executes-carey-dean-moore-for-murders-of-omaha-cab/article_c2332b24-145e-51b8-9bd3-d4b13e64b70c.html#1 | url-status = live }}</ref>

==Veterinary uses==
Diazepam is used as a short-term sedative and [[anxiolytic]] for cats and dogs,<ref name="Merck vet diazepam">{{cite web | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/190302.htm | title = Drugs Affecting Appetite (Monogastric) | publisher = The Merck Veterinary Manual | access-date = 4 January 2014 | archive-url = https://web.archive.org/web/20121028205743/http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm%2Fbc%2F190302.htm | archive-date = 28 October 2012 }}</ref> sometimes used as an appetite stimulant.<ref name="Merck vet diazepam" /><ref name="pmid10342284">{{cite journal | vauthors = Rahminiwati M, Nishimura M | title = Effects of delta 9-tetrahydrocannabinol and diazepam on feeding behavior in mice | journal = The Journal of Veterinary Medical Science | volume = 61 | issue = 4 | pages = 351–5 | date = April 1999 | pmid = 10342284 | doi = 10.1292/jvms.61.351 | doi-access = free }}</ref> It can also be used to stop seizures in dogs and cats.<ref name="Shell-2012">{{cite web | title = Anticonvulsants Used to Stop Ongoing Seizure Activity | url = http://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/anticonvulsants_used_to_stop_ongoing_seizure_activity.html#v3331734 | access-date = 10 January 2014 | vauthors = Shell L | date = March 2012 | quote = Dogs and Cats:<br />A variety of drugs can be used to stop seizures in dogs and cats.<br />Benzodiazepines:<br />Diazepam is the most common benzodiazepine used in dogs and cats to reduce motor activity and permit the placement of an IV catheter. | url-status=live | archive-url = https://web.archive.org/web/20140110200807/http://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/anticonvulsants_used_to_stop_ongoing_seizure_activity.html#v3331734 | archive-date = 10 January 2014 }}</ref>

==References==
{{Reflist}}

==Further reading==
* {{cite book | vauthors=Dean L | chapter=Diazepam Therapy and CYP2C19 Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK379740/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | title=Medical Genetics Summaries | display-editors=3 | publisher=[[National Center for Biotechnology Information]] (NCBI) | year=2016 | pmid=28520370 | id=Bookshelf ID: NBK379740 | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ }}

==External links==
{{Commons category|Diazepam}}
* {{cite web | title=Diazepam Nasal Spray | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a620026.html }}

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{{Anticonvulsants}}
{{Antidotes}}
{{Anxiolytics}}
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{{GABAA receptor positive allosteric modulators}}
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{{Benzodiazepines}}
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[[Category:21-Hydroxylase inhibitors]]
[[Category:Anxiolytics]]
[[Category:Benzodiazepines]]
[[Category:Chemical substances for emergency medicine]]
[[Category:Chloroarenes]]
[[Category:Euphoriants]]
[[Category:Drugs developed by Genentech]]
[[Category:Drugs developed by Hoffmann-La Roche]]
[[Category:Glycine receptor antagonists]]
[[Category:Hallucinogen antidotes]]
[[Category:Lactams]]
[[Category:TSPO ligands]]
[[Category:World Health Organization essential medicines]]
[[Category:Wikipedia medicine articles ready to translate]]