Flunitrazepam

File:Rohypnol.jpg

In countries where this drug is used, it is used for treatment of severe cases of sleeping problems, and in some countries as a preanesthetic agent. These were also the uses for which it was originally studied.{{cite journal | vauthors = Mattila MA, Larni HM | title = Flunitrazepam: a review of its pharmacological properties and therapeutic use | journal = Drugs | volume = 20 | issue = 5 | pages = 353–374 | date = November 1980 | pmid = 6108205 | doi = 10.2165/00003495-198020050-00002 | s2cid = 25151953 }}

It has also been administered as a concurrent dose for patients that are taking ketamine. Rohypnol lowers the side effects of the anesthetic (ketamine), resulting in less confusion in awakening states, less negative influence on pulse rate, and fewer fluctuations in blood pressure.{{cite journal | vauthors = Freuchen I, Ostergaard J, Kühl JB, Mikkelsen BO | title = Reduction of psychotomimetic side effects of Ketalar (ketamine) by Rohypnol (flunitrazepam). A randomized, double-blind trial | journal = Acta Anaesthesiologica Scandinavica | volume = 20 | issue = 2 | pages = 97–103 | date = 1976 | pmid = 7095 | doi = 10.1111/j.1399-6576.1976.tb05015.x | s2cid = 46172276 }}

Adverse effects of flunitrazepam include dependency, both physical and psychological; reduced sleep quality resulting in somnolence; and overdose, resulting in excessive sedation, impairment of balance and speech, respiratory depression or coma, and possibly death. Because of the latter, flunitrazepam is commonly used in suicide among the elderly.{{cite journal | vauthors = Carlsten A, Waern M, Holmgren P, Allebeck P | title = The role of benzodiazepines in elderly suicides | journal = Scandinavian Journal of Public Health | volume = 31 | issue = 3 | pages = 224–228 | year = 2003 | pmid = 12850977 | doi = 10.1080/14034940210167966 | publisher = SAGE Publications | s2cid = 24102880 }} When used in late pregnancy, it might cause hypotonia of the fetus.

Flunitrazepam, as with other benzodiazepines, can lead to drug dependence. Discontinuation may result in benzodiazepine withdrawal syndrome, characterised by seizures, psychosis, insomnia, and anxiety. Rebound insomnia, worse than baseline insomnia, typically occurs after discontinuation of flunitrazepam even from short-term single nightly dose therapy.{{cite journal | vauthors = Kales A, Scharf MB, Kales JD, Soldatos CR | title = Rebound insomnia. A potential hazard following withdrawal of certain benzodiazepines | journal = JAMA | volume = 241 | issue = 16 | pages = 1692–1695 | date = April 1979 | pmid = 430730 | doi = 10.1001/jama.241.16.1692 }}

Flunitrazepam may cause a paradoxical reaction in some individuals, including anxiety, aggressiveness, agitation, confusion, disinhibition, loss of impulse control, talkativeness, violent behavior, and even convulsions. Paradoxical adverse effects may even lead to criminal behaviour.{{cite journal | vauthors = Bramness JG, Skurtveit S, Mørland J | title = Flunitrazepam: psychomotor impairment, agitation and paradoxical reactions | journal = Forensic Science International | volume = 159 | issue = 2–3 | pages = 83–91 | date = June 2006 | pmid = 16087304 | doi = 10.1016/j.forsciint.2005.06.009 }}

{{See also|Hypotonia}}

Benzodiazepines such as flunitrazepam are lipophilic and rapidly penetrate membranes and, therefore, rapidly cross over into the placenta with significant uptake of the drug. Use of benzodiazepines including flunitrazepam in late pregnancy, especially high doses, may result in hypotonia, also known as floppy baby syndrome.{{cite journal | vauthors = Kanto JH | title = Use of benzodiazepines during pregnancy, labour and lactation, with particular reference to pharmacokinetic considerations | journal = Drugs | volume = 23 | issue = 5 | pages = 354–380 | date = May 1982 | pmid = 6124415 | doi = 10.2165/00003495-198223050-00002 | s2cid = 27014006 }}

Flunitrazepam impairs cognitive functions. This may appear as lack of concentration, confusion and anterograde amnesia—the inability to create memories while under the influence. It can be described as a hangover-like effect which can persist to the next day.{{cite journal | vauthors = Vermeeren A | title = Residual effects of hypnotics: epidemiology and clinical implications | journal = CNS Drugs | volume = 18 | issue = 5 | pages = 297–328 | year = 2004 | pmid = 15089115 | doi = 10.2165/00023210-200418050-00003 | s2cid = 25592318 }} It also impairs psychomotor functions similar to other benzodiazepines and nonbenzodiazepine hypnotic drugs; falls and hip fractures were frequently reported. The combination with alcohol increases these impairments. Partial, but incomplete tolerance develops to these impairments.{{cite journal | vauthors = Mets MA, Volkerts ER, Olivier B, Verster JC | title = Effect of hypnotic drugs on body balance and standing steadiness | journal = Sleep Medicine Reviews | volume = 14 | issue = 4 | pages = 259–267 | date = August 2010 | pmid = 20171127 | doi = 10.1016/j.smrv.2009.10.008 }}

Other adverse effects include:

• Slurred speech
• Gastrointestinal disturbances, lasting 12 or more hours
• Vomiting
• Respiratory depression in higher doses

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, in alcohol- or drug-dependent individuals, and in individuals with comorbid psychiatric disorders.{{cite journal | vauthors = Authier N, Balayssac D, Sautereau M, Zangarelli A, Courty P, Somogyi AA, Vennat B, Llorca PM, Eschalier A | display-authors = 6 | title = Benzodiazepine dependence: focus on withdrawal syndrome | journal = Annales Pharmaceutiques Françaises | volume = 67 | issue = 6 | pages = 408–413 | date = November 2009 | pmid = 19900604 | doi = 10.1016/j.pharma.2009.07.001 }}

Impairment of driving skills with a resultant increased risk of road traffic accidents is probably the most important adverse effect. This side-effect is not unique to flunitrazepam but also occurs with other hypnotic drugs. Flunitrazepam seems to have a particularly high risk of road traffic accidents compared to other hypnotic drugs. Extreme caution should be exercised by drivers after taking flunitrazepam.{{cite journal | vauthors = Gustavsen I, Bramness JG, Skurtveit S, Engeland A, Neutel I, Mørland J | title = Road traffic accident risk related to prescriptions of the hypnotics zopiclone, zolpidem, flunitrazepam and nitrazepam | journal = Sleep Medicine | volume = 9 | issue = 8 | pages = 818–822 | date = December 2008 | pmid = 18226959 | doi = 10.1016/j.sleep.2007.11.011 | hdl-access = free | hdl = 10852/34650 }}UK Dept. of Transport. July 2014. {{cite web | url = https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/325275/healthcare-profs-drug-driving.pdf | title = Guidance for healthcare professionals on drug driving | work = The Department for Transport | date = 2014 | location = London }}

The use of flunitrazepam in combination with alcoholic beverages synergizes the adverse effects, and can lead to toxicity and death.{{cite web | url = http://www.emcdda.europa.eu/publications/drug-profiles/benzodiazepine | title = Benzodiazepines drug profile | date = 8 January 2015 | work = European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) }}

{{See also|Benzodiazepine overdose}}

Flunitrazepam is a drug that is frequently involved in drug intoxication, including overdose.{{cite journal | vauthors = Zevzikovas A, Kiliuviene G, Ivanauskas L, Dirse V | title = [Analysis of benzodiazepine derivative mixture by gas-liquid chromatography] | journal = Medicina | volume = 38 | issue = 3 | pages = 316–320 | year = 2002 | pmid = 12474705 }}{{cite journal | vauthors = Jonasson B, Saldeen T | title = Citalopram in fatal poisoning cases | journal = Forensic Science International | volume = 126 | issue = 1 | pages = 1–6 | date = March 2002 | pmid = 11955823 | doi = 10.1016/S0379-0738(01)00632-6 }} Overdose of flunitrazepam may result in excessive sedation, or impairment of balance or speech. This may progress in severe overdoses to respiratory depression or coma and possibly death. The risk of overdose is increased if flunitrazepam is taken in combination with CNS depressants such as ethanol (alcohol) and opioids. Flunitrazepam overdose responds to the GABA_A receptor antagonist flumazenil, which thus can be used as a treatment.

As of 2016, blood tests can identify flunitrazepam at concentrations of as low as 4 nanograms per millilitre; the elimination half life of the drug is 4–12 hours. For urine samples, metabolites can be identified for 60 hours to 28 days, depending on the dose and analytical method used. Hair and saliva can also be analyzed; hair is useful when a long time has transpired since ingestion, and saliva for workplace drug tests.

Flunitrazepam can be measured 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 flunitrazepam concentrations are usually in a range of 5–20 μg/L in persons receiving the drug therapeutically as a nighttime hypnotic, 10–50 μg/L in those arrested for impaired driving and 100–1000 μg/L in victims of acute fatal overdosage. Urine is often the preferred specimen for routine substance use monitoring purposes. The presence of 7-aminoflunitrazepam, a pharmacologically active metabolite and in vitro degradation product, is useful for confirmation of flunitrazepam ingestion. In postmortem specimens, the parent drug may have been entirely degraded over time to 7-aminoflunitrazepam.{{cite journal | vauthors = Jones AW, Holmgren A, Kugelberg FC | 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 | s2cid = 25511804 }}{{cite journal | vauthors = Robertson MD, Drummer OH | title = Stability of nitrobenzodiazepines in postmortem blood | journal = Journal of Forensic Sciences | volume = 43 | issue = 1 | pages = 5–8 | date = January 1998 | pmid = 9456517 | doi = 10.1520/JFS16081J}}{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | date = 2008 | pages = 633–635 }} Other metabolites include desmethylflunitrazepam and 3-hydroxydesmethylflunitrazepam.

The main pharmacological effects of flunitrazepam are the enhancement of GABA, an inhibitory neurotransmitter, at various GABA receptors. All benzodiazepines work by enhancing the effect of GABA receptors, which, when active, allow chloride ions to enter the neuron.{{cite web | vauthors = Santos E |title=Flunitrazepam (Rohypnol) Fact Sheet & Harm Reduction Guide |url=https://tripsitter.com/benzodiazepines/flunitrazepam/ |website=Tripsitter |date=October 13, 2022 |access-date=15 November 2023}} Negative ions such as chloride inhibit the ability of neurons to fire. It is this stimulation of GABA receptors which is responsible for the depressant effects of benzodiazepines. Flunitrazepam shows high affinity for the α-5 subunit of the GABA-A receptor, which causes some of its unique side effects, such as amnesia.

While 80% of flunitrazepam that is taken orally is absorbed, bioavailability in suppository form is closer to 50%.{{cite journal | vauthors = Cano JP, Soliva M, Hartmann D, Ziegler WH, Amrein R | title = Bioavailability from various galenic formulations of flunitrazepam | journal = Arzneimittel-Forschung | volume = 27 | issue = 12 | pages = 2383–2388 | year = 1977 | pmid = 23801 | id = rohypnol }}

Flunitrazepam has a long half-life of 18–26 hours, which means that flunitrazepam's effects after nighttime administration persist throughout the next day. This is due to the production of active metabolites. These metabolites further increase the duration of drug action compared to benzodiazepines that produce nonactive metabolites.{{cite journal | vauthors = Griffin CE, Kaye AM, Bueno FR, Kaye AD | title = Benzodiazepine pharmacology and central nervous system-mediated effects | journal = The Ochsner Journal | volume = 13 | issue = 2 | pages = 214–223 | date = 2014 | pmid = 23789008 | pmc = 3684331 }}

Flunitrazepam is lipophilic and is metabolised by the liver via oxidative pathways. The enzyme CYP3A4 is the main enzyme in its phase 1 metabolism in human liver microsomes.{{cite journal | vauthors = Hesse LM, Venkatakrishnan K, von Moltke LL, Shader RI, Greenblatt DJ | title = CYP3A4 is the major CYP isoform mediating the in vitro hydroxylation and demethylation of flunitrazepam | journal = Drug Metabolism and Disposition | volume = 29 | issue = 2 | pages = 133–140 | date = February 2001 | pmid = 11159802 | url = http://dmd.aspetjournals.org/cgi/content/abstract/29/2/133 }}

Flunitrazepam is classed as a nitro-benzodiazepine. It is the fluorinated N-methyl derivative of nitrazepam. Other nitro-benzodiazepines include nitrazepam (the parent compound), nimetazepam (methylamino derivative) and clonazepam (2ʹ-chlorinated derivative).{{cite journal | vauthors = Robertson MD, Drummer OH | title = Postmortem drug metabolism by bacteria | journal = Journal of Forensic Sciences | volume = 40 | issue = 3 | pages = 382–386 | date = May 1995 | pmid = 7782744 | doi = 10.1520/JFS13791J }}

Flunitrazepam has a melting point of around 170 degrees Celsius.{{cite journal |last1=Sternbach |display-authors=etal |first1=L. |title=Quinazolines and 1,4-Benzodiazepines. X.1 Nitro-Substituted 5-Phenyl-1,4-benzodiazepine Derivatives2 |journal=Journal of Medical Chemistry |date=1 May 1963 |volume=6 |issue=3 |pages=261–265 |doi=10.1021/jm00339a010 |pmid=14185980 |url=https://pubs.acs.org/doi/abs/10.1021/jm00339a010 |access-date=15 November 2023}}

Flunitrazepam was discovered at Roche as part of the benzodiazepine work led by Leo Sternbach; the patent application was filed in 1960 and it was first marketed in 1972.

{{cite book | vauthors = Alapi EM, Fischer J | chapter = Table of Selected Analogue Classes | veditors = Fische J, Ganellin CR|title=Analogue-Based Drug Discovery |date=2006 |publisher=Wiley-VCH |location=Weinheim |isbn=978-3-527-60749-5 | page = [https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA537 537] }}

{{cite journal | vauthors = Bryan J | title = Landmark drugs: The discovery of benzodiazepines and the adverse publicity that followed. | journal = The Pharmaceutical Journal | date = September 2009 | volume = 283 | page = 305 | url = http://www.pharmaceutical-journal.com/opinion/comment/landmark-drugs-the-discovery-of-benzodiazepines-and-the-adverse-publicity-that-followed/10978453.article | archive-url = https://web.archive.org/web/20151120033823/http://www.pharmaceutical-journal.com/opinion/comment/landmark-drugs-the-discovery-of-benzodiazepines-and-the-adverse-publicity-that-followed/10978453.article | archive-date = 20 November 2015 }}

Due to use of the drug for date rape and recreation, in 1998 Roche modified the formulation to give lower doses, make it less soluble, and add a blue dye for easier detection in drinks.{{cite book | vauthors = Kiss B, Bodoki E, Pop A, Loghin F | chapter = Chapter 48: Assays for Flunitrazepam | veditors = Preedy VR |title=Neuropathology of drug addictions and substance misuse. Volume 2, Stimulants, club and dissociative drugs, hallucinogens, steroids, inhalants, and international aspects |date=2016 |location=London | publisher = Academic Press |isbn=978-0-12-800375-6 | chapter-url = https://books.google.com/books?id=zu5eBwAAQBAJ&pg=PA513 | page = 513}} It was never marketed in the United States, and by 2016 had been withdrawn from the markets in Spain, France, Norway, Germany, and the United Kingdom.

File:Hypnodorm.jpg

File:rohypnol2.jpg

A 1989 article in the European Journal of Clinical Pharmacology reports that benzodiazepines accounted for 52% of prescription forgeries in Sweden, suggesting that benzodiazepines were a major prescription drug class of abuse. Nitrazepam accounted for 13% of forged prescriptions, and accounted for 44% of forgeries specifically for benzodiazepines while flunitrazepam, diazepam, and oxazepam accounted for the majority of the rest of benzodiazepine forgeries. Prescription forgeries for other benzodiazepines marketed in Sweden (alprazolam, clonazepam, lorazepam, clobazam, and bromazepam) were negligible. When calculated in relation to utilization, the narcotic analgesics codeine, pentazocine, and ketobemidone were at the top of the list for the highest number of overall prescription forgeries, suggesting a higher abuse potential of these drugs.{{cite journal | vauthors = Bergman U, Dahl-Puustinen ML | title = Use of prescription forgeries in a drug abuse surveillance network | journal = European Journal of Clinical Pharmacology | volume = 36 | issue = 6 | pages = 621–623 | date = November 1989 | pmid = 2776820 | doi = 10.1007/BF00637747 | s2cid = 19770310 }} In neighboring Finland, temazepam accounts for roughly 40–50% benzodiazepine prescription forgeries annually, while flunitrazepam accounts for approximately ~15% of benzodiazepine prescription forgeries.{{cite web|title=Classification of controlled drugs|url=http://www.emcdda.europa.eu/html.cfm/index146601EN.html|publisher=EMCDDA|access-date=30 June 2022}}

Flunitrazepam and other sedative hypnotic drugs are detected frequently in cases of people suspected of driving under the influence of drugs. Other benzodiazepines and nonbenzodiazepines (anxiolytic or hypnotic) such as zolpidem and zopiclone (as well as cyclopyrrolones, imidazopyridines, and pyrazolopyrimidines) are also found in high numbers of suspected drugged drivers. Many drivers have blood levels far exceeding the therapeutic dose range, suggesting a high degree of potential for addiction for benzodiazepines and similar drugs.{{cite journal | vauthors = Jones AW, Holmgren A, Kugelberg FC | 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 = 248–260 | date = April 2007 | pmid = 17417081 | doi = 10.1097/FTD.0b013e31803d3c04 | s2cid = 25511804 }}

In studies in Sweden, flunitrazepam was the second most common drug used in suicides, being found in about 16% of cases.{{cite journal | vauthors = Jonasson B, Jonasson U, Saldeen T | title = Among fatal poisonings dextropropoxyphene predominates in younger people, antidepressants in the middle aged and sedatives in the elderly | journal = Journal of Forensic Sciences | volume = 45 | issue = 1 | pages = 7–10 | date = January 2000 | pmid = 10641912 | doi = 10.1520/JFS14633J }} In a retrospective Swedish study of 1,587 deaths, in 159 cases benzodiazepines were found. In suicides when benzodiazepines were implicated, the benzodiazepines flunitrazepam and nitrazepam occurred in significantly higher concentrations compared to natural deaths. Of the 159 deaths where any benzodiazepines were found, 4 deaths were caused by benzodiazepines alone (in the other 155 cases, benzodiazepines were combined with something else). One conclusion of the study was that flunitrazepam and nitrazepam might be more toxic than other benzodiazepines available in the Swedish market.{{cite journal | vauthors = Ericsson HR, Holmgren P, Jakobsson SW, Lafolie P, De Rees B | title = [Benzodiazepine findings in autopsy material. A study shows interacting factors in fatal cases] | journal = Läkartidningen | volume = 90 | issue = 45 | pages = 3954–3957 | date = November 1993 | pmid = 8231567 }}{{cite journal | vauthors = Drummer OH, Syrjanen ML, Cordner SM | title = Deaths involving the benzodiazepine flunitrazepam | journal = The American Journal of Forensic Medicine and Pathology | volume = 14 | issue = 3 | pages = 238–243 | date = September 1993 | pmid = 8311057 | doi = 10.1097/00000433-199309000-00012 | s2cid = 28937806 }}

{{Main|Drug facilitated sexual assault}}

Flunitrazepam is known to induce anterograde amnesia in sufficient doses; individuals are unable to remember certain events that they experienced while under the influence of the drug, which complicates investigations.{{cite news | vauthors = Liljesson S | date = 3 June 1999 |url= http://drugnews.nu/article.asp?id=199 |title=Bankrånare stärkte sig med Rohypnol?|publisher=DrugNews |access-date=May 19, 2006|archive-url= https://web.archive.org/web/20070929165033/http://drugnews.nu/article.asp?id=199|archive-date=September 29, 2007|url-status=dead}}{{cite news|url=http://www.expressen.se/index.jsp?d=737&a=116288|title=Mijailovic var påverkad av våldsdrog|newspaper=Expressen}} This effect could be particularly dangerous if flunitrazepam is used to aid in the commission of sexual assault; victims may be unable to clearly recall the assault, the assailant, or the events surrounding the assault.

While use of flunitrazepam in sexual assault has been prominent in the media, as of 2015 it appears to be fairly rare, and use of alcohol and other benzodiazepine drugs in date rape appears to be a larger but underreported problem.

In a 2001 study, the benzodiazepines midazolam and temazepam were the two most common benzodiazepines utilized for date rape.{{cite book | vauthors = El-Sohly MA, Lee LF, Holzhauer LB, Salamone SJ | chapter = Analysis of Urine Samples in Cases of Alleged Sexual Assault | title = Benzodiazepines and GHB | series = Forensic Science and Medicine | year = 2001 | pages = 127–144 | publisher = Humana Press |doi=10.1007/978-1-59259-109-1 | doi-broken-date = November 1, 2024 |isbn=1-59259-109-4 |chapter-url = https://link.springer.com/chapter/10.1007/978-1-59259-109-1_7}}

In the United Kingdom, the use of flunitrazepam and other "date rape" drugs have also been connected to stealing from sedated victims. An activist quoted by a British newspaper estimated that up to 2,000 individuals are robbed each year after being spiked with powerful sedatives,{{cite news| url=https://www.theguardian.com/crime/article/0,2763,1376956,00.html |work=The Guardian |location=London |title='Rape drug' used to rob thousands | vauthors = Thompson T |date=December 19, 2004 |access-date=May 2, 2010}} making drug-assisted robbery a more commonly reported problem than drug-assisted rape.

Flunitrazepam is a Schedule III drug under the international Convention on Psychotropic Substances of 1971.{{cite web | publisher = International Narcotics Control Board | url = http://www.incb.org/documents/Psychotropics/greenlist/Green_list_ENG_2015_new.pdf | title = List of Psychotropic Substances under International Control | archive-url = https://web.archive.org/web/20170713091834/http://www.incb.org/documents/Psychotropics/greenlist/Green_list_ENG_2015_new.pdf | archive-date= 13 July 2017 | work = Green List | edition = 26th | date = 2015 }}

• In Australia, as of 2013 the drug was authorized for prescribing for severe cases of insomnia but was restricted as a Schedule 8 medicine.{{cite web| date= August 13, 2004| url= http://www.health.wa.gov.au/notifications/authorisations/drugs/flunitrazepam.cfm| title= Authorisation to Supply or Prescribe Drugs of Addiction: Flunitrazepam| work= Statutory Medical Notifications| publisher= Department of Health, Government of Western Australia| access-date= 2006-03-13| archive-url = https://web.archive.org/web/20060828184311/http://www.health.wa.gov.au/notifications/authorisations/drugs/flunitrazepam.cfm |archive-date = August 28, 2006}}
• In France, as of 2016 flunitrazepam was not marketed.
• In Germany, as of 2016 flunitrazepam is an Anlage III Betäubungsmittel (controlled substance which is allowed to be marketed and prescribed by physicians under specific provisions) and is available on a special narcotic drug prescription as the Rohypnol 1 mg film-coated tablets and several generic preparations (November 2016).{{Cite web|url=https://www.gelbe-liste.de/wirkstoffe/flunitrazepam_2624|title = Flunitrazepam - Anwendung, Wirkung, Nebenwirkungen | work = Gelbe Liste | publisher = Vidal MMI Germany GmbH }}
• In Ireland, flunitrazepam is a Schedule 3 controlled substance with strict restrictions.{{cite web | url = http://www.irishstatutebook.ie/1993/en/si/0342.html | work = Irish Statute Book, Statutory Instruments | title = S.I. No. 342/1993 — Misuse of Drugs (Amendment) Regulations | date = 1993 }}
• In Japan, flunitrazepam is marketed by Japanese pharmaceutical company Chugai under the trade name Rohypnol and is indicated for the treatment of insomnia as well as used for preanesthetic medication.{{cite web |url=http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=1051 |title=Kusuri-no-Shiori Drug Information Sheet |date=October 2015 |publisher=RAD-AR Council, Japan |access-date=2016-06-13 |archive-date=March 3, 2016 |archive-url=https://web.archive.org/web/20160303232158/http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=1051 |url-status=dead }}
• In Mexico, Rohypnol is legally available.{{cite web |title=What is Rohypnol? |url=https://www.12southrecovery.us/post/what-is-rohypnol |website=12 South Recovery |date=May 27, 2019 |access-date=24 January 2021}}
• In Norway, on January 1, 2003, flunitrazepam was moved up one level in the schedule of controlled drugs and, on August 1, 2004, the manufacturer Roche removed Rohypnol from the market there altogether.{{cite journal | vauthors = Bramness JG, Skurtveit S, Furu K, Engeland A, Sakshaug S, Rønning M | title = [Changes in the sale and use of flunitrazepam in Norway after 1999] | journal = Tidsskrift for den Norske Laegeforening | volume = 126 | issue = 5 | pages = 589–590 | date = February 2006 | pmid = 16505866 }}
• In South Africa, Rohypnol is classified as a Schedule 6 drug.{{cite web| date= October 11, 2006| url= http://www.drugaware.co.za/rohypnol.html | title = Rohypnol | work = Drug Wars – About Drugs}} It is available by prescription only, and restricted to 1 mg doses.

File:Iceland Flunitrazepam Mylan 1mg.png

• In Iceland, flunitrazepam is a controlled substance available from Mylan. It is prescribed for severe insomnia and is sometimes used before surgery to induce a calm, relaxed state of mind for the patient.{{Cite web|url=https://www.lyfja.is/lyfjabokin/lyf/FlunitrazepamMylan|title=Flunitrazepam Mylan|website=Lyfja - Lifið heil|language=is|access-date=2020-02-27}}
• In Sweden, flunitrazepam is a List II drug (substances with medicinal uses) under the Narcotics Control Act (1968).{{cite web |url=https://www.lakemedelsverket.se/sv/sok-lakemedelsfakta/substans?id=E4POCOU9OKGVERT1 |title=Flunitrazepam |publisher=Medical Products Agency |access-date=February 17, 2022 |location=Sweden |language=Swedish}} It was previously available from Mylan,{{Cite web|url=http://www.fass.se/LIF/produktfakta/substance_products.jsp?substanceId=IDE4POCOU9OKGVERT1|title = Substans | work = Farmaceutiska Specialiteter i Sverige (FASS) Allmänhet}} but has been removed from the market in January 2020.{{Cite web |url= https://janusinfo.se/nyheter/nyheter/2019/flunitrazepamutgar.5.1902def216e9304699285304.html |title=Flunitrazepam utgår | trans-title = Flunitrazepam is discontinued | work = Janusinfo | location = Stockholm | language = Swedish }}
• In the United Kingdom, flunitrazepam is not licensed for medical use and is a controlled drug under Schedule 3 and Class C.{{cite web | url = https://www.gov.uk/government/publications/controlled-drugs-list--2/list-of-most-commonly-encountered-drugs-currently-controlled-under-the-misuse-of-drugs-legislation | title = List of most commonly encountered drugs currently controlled under the misuse of drugs legislation | date = 8 August 2022 | work = Gov.uk }}
• In the United States, the drug has not been approved by the Food and Drug Administration and is considered to be an illegal drug; as of 2016 it is Schedule IV.DEA [Lists of Scheduling Actions Controlled Substances Regulated Chemicals May 2016] {{UnitedStatesCode|21|841}} and {{UnitedStatesCode|21|952}} provide for punishment for the importation and distribution of up to 20 years in prison and a fine; possession is punishable by three years and a fine.{{cite web | work = Center for Substance Abuse Research | publisher = University of Maryland | url = http://www.cesar.umd.edu/cesar/drugs/rohypnol.asp | title = Flunitrazepam (Rohypnol) | archive-url = https://web.archive.org/web/20160109205146/http://www.cesar.umd.edu/cesar/drugs/rohypnol.asp | archive-date= January 9, 2016 | date = 29 October 2013 }} Travelers travelling into the United States are limited to a 30-day supply. The drug must be declared to US Customs upon arrival. If a valid prescription cannot be produced, the drug may be subject to Customs search and seizure, and the traveler may face criminal charges or deportation.

Flunitrazepam is marketed under many brand names in the countries where it is legal.{{cite web | work = Drugs.com | url = https://www.drugs.com/international/flunitrazepam.html | title = International brands for Flunitrazepam | access-date = 13 April 2016 }} It also has many street names, including "roofie" and "ruffie". It is also known as Circles, Forget Me Pill, La Rocha, Lunch Money Drug, Mexican Valium, Pingus, R2, and Roach 2.{{cite web |title=Rohypnol |url=https://www.dea.gov/factsheets/rohypnol |website=United States Drug Enforcement Administration |access-date=October 18, 2020}}

{{Reflist|30em}}

{{Commons category|Flunitrazepam}}

• [http://www.chm.bris.ac.uk/motm/rohypnol/rohypnolh.htm Molecule of the Month]
• [https://web.archive.org/web/20060516010858/http://www.hhs.gov/asl/testify/t990311b.html Statement on "Date Rape" Drugs by Associate Director for Domestic and International Drug Control, Office of Health Affairs, FDA, before Congress. Mar. 11, 1999.]

{{Benzodiazepines}}

{{Hypnotics and sedatives}}

{{GABAAR PAMs}}

{{Glycinergics}}

{{Authority control}}

Category:GABAA receptor positive allosteric modulators

Category:Glycine receptor antagonists

Category:Drugs developed by Hoffmann-La Roche

Category:Lactams

Category:Nitrobenzodiazepines

Category:2-Fluorophenyl compounds

Category:Drug culture

Category:Drug-facilitated sexual assault