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'''Flunitrazepam''' (trade name '''Rohypnol''') is a [[psychoactive class::depressant]] substance of the [[chemical class::benzodiazepine]] class that produces primarily [[hypnotic]] and [[amnesic]], but also [[anxiolytic]], [[anticonvulsant]] and [[sedative]] effects when [[administered]].<ref name="Mandroili2008">{{cite journal | vauthors=((Mandrioli, R.)), ((Mercolini, L.)), ((Raggi, M. A.)) | journal=Current Drug Metabolism | title=Benzodiazepine metabolism: an analytical perspective | volume=9 | issue=8 | pages=827–844 | date= October 2008 | issn=1389-2002 | doi=10.2174/138920008786049258}}</ref>
{{headerpanel|{{proofread}}{{Approval}}}}
Flunitrazepam was first synthesized in 1972 by Hoffmann-La Roche. It is used for the short term treatment of [[insomnia]] and as a preoperative sedative in some countries. It is approximately 10 times more potent by weight than [[diazepam]].
{{SummarySheet}}
{{SubstanceBox/Example}}
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Users should note that [[Benzodiazepine#Discontinuation|the sudden discontinuation of benzodiazepines]] can be potentially dangerous or life-threatening for individuals using regularly for extended periods of time, sometimes resulting in seizures or death.<ref name="Lann2009">{{cite journal | vauthors=((Lann, M. A.)), ((Molina, D. K.)) | journal=The American Journal of Forensic Medicine and Pathology | title=A fatal case of benzodiazepine withdrawal | volume=30 | issue=2 | pages=177–179 | date= June 2009 | issn=1533-404X | doi=10.1097/PAF.0b013e3181875aa0}}</ref> It is highly recommended to taper one's dose by gradually lowering the amount taken each day for a prolonged period of time instead of stopping abruptly.<ref>{{cite journal | vauthors=((Kahan, M.)), ((Wilson, L.)), ((Mailis-Gagnon, A.)), ((Srivastava, A.)) | journal=Canadian Family Physician | title=Canadian guideline for safe and effective use of opioids for chronic noncancer pain. Appendix B-6: Benzodiazepine Tapering | volume=57 | issue=11 | pages=1269–1276 | date= November 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215603/ | issn=0008-350X}}</ref>
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'''Flunitrazepam''' (trade name '''Rohypnol''') was first synthesized in 1972 by Hoffmann-La Roche and is an intermediate-acting hypnotic of the [[chemical class::benzodiazepine]] chemical class. It possesses [[anxiolytic]], [[anticonvulsant]], [[sedative]], [[hypnotic]], [[psychoactive class::depressant]] and [[amnestic]] properties.<ref>Benzodiazepine metabolism: an analytical perspective (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614</ref> It is used for the short term treatment of [[insomnia]] and as a preoperative sedative in some countries, these were also the indications in which it was originally studied. Flunitrazepam is approximately 10 times more potent by weight than [[Diazepam]].
It's worth noting that [[Benzodiazepine#Discontinuation|the sudden discontinuation of benzodiazepines]] can be potentially dangerous or life-threatening for individuals using regularly for extended periods of time, sometimes resulting in seizures or death.<ref>A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812</ref> It is highly recommended to taper one's dose by gradually lowering the amount taken each day for a prolonged period of time instead of stopping abruptly.<ref>Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain - Appendix B-6: Benzodiazepine Tapering | http://nationalpaincentre.mcmaster.ca/opioid/cgop_b_app_b06.html</ref>
==History and culture==
==History and culture==
{{historyStub}}
{{historyStub}}
Flunitrazepam was discovered at Roche as part of the benzodiazepine work led by Leo Sternbach and it was first marketed in 1974. It first entered the commerical market in Europe in 1975 as Rohypnol and In the 1980's it began to be available in other countries. <ref>https://en.wikipedia.org/wiki/Flunitrazepam</ref>
Flunitrazepam was discovered at Roche as part of the benzodiazepine work led by Leo Sternbach. It was first marketed in 1974 and entered the commerical market in Europe in 1975 under the name Rohypnol. In the 1980's it began to be available in other countries. <ref name="Wikipedia2022">{{Citation | year=2022 | title=Flunitrazepam | url=https://en.wikipedia.org/w/index.php?title=Flunitrazepam&oldid=1100552588}}</ref>
In 1998, due to the abuse of the drug for date rape and recreation, Roche modified their 1mg tablets to make them less soluble and added a blue dye for easier detection in drinks. <ref>https://wiki.tripsit.me/wiki/Flunitrazepam</ref>
It may be better known as the date-rape drug Rohypnol (with the street name “roofie”). In 1998, due to the abuse of the drug and recreation, Roche modified their 1 mg tablets to make them less soluble and added a blue dye for easier detection in drinks. <ref>{{Citation | title=Flunitrazepam - TripSit wiki | url=https://wiki.tripsit.me/wiki/Flunitrazepam}}</ref>
In studies in Sweden, flunitrazepam was the second most common drug used in suicides, being found in about 16% of cases. In a retrospective Swedish study of 1587 deaths, in 159 cases benzodiazepines were found. In suicides when benzodiazepines were implicated, the benzodiazepines flunitrazepam and [[Nitrazepam]] were occurring in significantly higher concentrations, compared to natural deaths. <ref>https://en.wikipedia.org/wiki/Flunitrazepam#Suicide</ref>
In studies in Sweden, flunitrazepam was the second most common drug used in suicides, being found in about 16% of cases. In a retrospective Swedish study of 1587 deaths, in 159 cases benzodiazepines were found. In suicides when benzodiazepines were implicated, the benzodiazepines flunitrazepam and [[nitrazepam]] were occurring in significantly higher concentrations, compared to natural deaths. <ref name="Wikipedia2022"/>
==Chemistry==
==Chemistry==
Flunitrazepam is a drug of the benzodiazepine class. Benzodiazepine drugs contain a benzene ring fused to a diazepine ring, which is a seven membered ring with the two nitrogen constituents located at R<sub>1</sub> and R<sub>4</sub>.
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).<ref>{{cite journal | vauthors=((Robertson, M. D.)), ((Drummer, O. H.)) | journal=Journal of Forensic Sciences | title=Postmortem drug metabolism by bacteria | volume=40 | issue=3 | pages=382–386 | date= May 1995 | issn=0022-1198}}</ref>
==Pharmacology==
==Pharmacology==
Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter [[GABA|gamma aminobutyric acid (GABA)]] by acting on its [[receptor]]s.<ref>Benzodiazepine interactions with GABA receptors (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6147796</ref> As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the [[sedating]] (or [[anxiety suppression|calming effects]]) of Flunitrazepam on the nervous system.
Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter [[GABA|gamma aminobutyric acid (GABA)]] by acting on its [[receptor]]s.<ref>{{cite journal | vauthors=((Haefely, W.)) | journal=Neuroscience Letters | title=Benzodiazepine interactions with GABA receptors | volume=47 | issue=3 | pages=201–206 | date=29 June 1984 | issn=0304-3940 | doi=10.1016/0304-3940(84)90514-7}}</ref> As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the [[sedating]] (or [[anxiety suppression|calming effects]]) of Flunitrazepam on the nervous system.
The [[anticonvulsant]] properties of benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.<ref>Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/2450203</ref>
The [[anticonvulsant]] properties of benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.<ref>{{cite journal | vauthors=((McLean, M. J.)), ((Macdonald, R. L.)) | journal=The Journal of Pharmacology and Experimental Therapeutics | title=Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture | volume=244 | issue=2 | pages=789–795 | date= February 1988 | issn=0022-3565}}</ref>
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). This effect could be particularly dangerous, if flunitrazepam is used to aid in the commission of sexual assault, because victims may be unable to clearly recall the assault, the assailant, or the events surrounding the assault. <ref>https://en.wikipedia.org/wiki/Flunitrazepam#Drug-facilitated_sexual_assault</ref>
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). This effect could be particularly dangerous, if flunitrazepam is used to aid in the commission of sexual assault, because victims may be unable to clearly recall the assault, the assailant, or the events surrounding the assault. <ref name="Wikipedia2022"/>
80% of the flunitrazepam that is taken orally is absorbed but the bioavailability in suppository form is closer to 50%. <ref>https://en.wikipedia.org/wiki/Flunitrazepam#Pharmacology</ref>
80% of the flunitrazepam that is taken orally is absorbed but the bioavailability in suppository form is closer to 50%. <ref name="Wikipedia2022"/>
==Subjective effects==
==Subjective effects==
{{Preamble/SubjectiveEffects}}
{{Preamble/SubjectiveEffects}}
The general head space of flunitrazepam is described as one of intense sedation, sleepiness, relaxation, anxiety suppression, memory suppression and decreased inhibition similar to the headspace of higher doses of [[diazepam]] and [[temazepam]].
{{effects/base
{{effects/base
|{{effects/physical|
|{{effects/physical|
*'''[[Effect::Sedation]]''' - In terms of energy level alterations, flunitrazepam has the potential to be extremely sedating and often results in an overwhelmingly lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness.
*'''[[Effect::Sedation]]''' - Flunitrazepam can produce extreme sedation and often results in an overwhelmingly lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness.
*'''[[Effect::Dizziness]]'''
*'''[[Effect::Dizziness]]'''
*'''[[Effect::Nausea]]'''
*'''[[Effect::Nausea]]'''
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{{effects/paradoxical|
{{effects/paradoxical|
Paradoxical reactions to [[benzodiazepines]] such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%).<ref>http://www.ncbi.nlm.nih.gov/pubmed/18922233 | Saïas T, Gallarda T | Paradoxical aggressive reactions to benzodiazepine use: a review</ref><ref>Paton C | Benzodiazepines and disinhibition: a review | Psychiatr Bull R Coll Psychiatr | http://pb.rcpsych.org/cgi/reprint/26/12/460.pdf</ref>
Paradoxical reactions to [[benzodiazepines]] such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%).<ref>{{cite journal | vauthors=((Saïas, T.)), ((Gallarda, T.)) | journal=L’Encephale | title=[Paradoxical aggressive reactions to benzodiazepine use: a review] | volume=34 | issue=4 | pages=330–336 | date= September 2008 | issn=0013-7006 | doi=10.1016/j.encep.2007.05.005}}</ref><ref>{{cite journal | vauthors=((Paton, C.)) | journal=Psychiatric Bulletin | title=Benzodiazepines and disinhibition: a review | volume=26 | issue=12 | pages=460–462 | date= December 2002 | url=https://www.cambridge.org/core/journals/psychiatric-bulletin/article/benzodiazepines-and-disinhibition-a-review/421AF197362B55EDF004700452BF3BC6 | issn=0955-6036 | doi=10.1192/pb.26.12.460}}</ref>
These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.<ref>Bond AJ | Drug-induced behavioural disinhibition: incidence, mechanisms and therapeutic implications | CNS Drugs</ref><ref>Drummer OH | Benzodiazepines—effects on human performance and behavior | Forensic Sci Rev</ref>
These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.<ref>{{cite journal | vauthors=((Bond, A. J.)) | journal=CNS Drugs | title=Drug- Induced Behavioural Disinhibition | volume=9 | issue=1 | pages=41–57 | date=1 January 1998 | url=https://doi.org/10.2165/00023210-199809010-00005 | issn=1179-1934 | doi=10.2165/00023210-199809010-00005}}</ref><ref>{{cite journal | vauthors=((Drummer, O. H.)) | journal=Forensic Science Review | title=Benzodiazepines - Effects on Human Performance and Behavior | volume=14 | issue=1–2 | pages=1–14 | date= February 2002 | issn=1042-7201}}</ref>
}}
}}
|{{effects/cognitive|
|{{effects/cognitive|
The cognitive effects of flunitrazepam can be broken down into several components which progressively intensify proportional to dosage. The general head space of flunitrazepam is described by many as one of intense sedation, relaxation, anxiety suppression and decreased inhibition similar to [[Diazepam]] and [[Temazepam]]. It contains a large number of typical [[Psychoactive class::depressant]] cognitive effects.
The cognitive effects of flunitrazepam can be broken down into several components which progressively intensify proportional to dosage. It contains a large number of typical [[Psychoactive class::depressant]] cognitive effects.
The most prominent of these cognitive effects generally include:
The most prominent of these cognitive effects generally include:
*'''[[Effect::Amnesia]]'''
*'''[[Effect::Amnesia]]''' - Flunitrazolam can cause considerable anmesia.
*'''[[Effect::Cognitive euphoria]]''' - The cognitive euphoria felt on flunitrazepam is significantly stronger than that felt on other [[benzodiazepine |benzodiazepines]] such as [[alprazolam]].
*'''[[Effect::Cognitive euphoria]]''' - The cognitive euphoria felt on flunitrazepam is significantly stronger than that felt on other [[benzodiazepine |benzodiazepines]] such as [[alprazolam]].
*'''[[Effect::Anxiety suppression]]'''
*'''[[Effect::Anxiety suppression]]'''
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*'''[[Effect::Confusion]]''' - At heavy doses, flunitrazepam can cause confusion. This effect is a result of the drug suppressing basic cognitive functions at heavy doses, such as comprehension, memory, and reasoning skills.
*'''[[Effect::Confusion]]''' - At heavy doses, flunitrazepam can cause confusion. This effect is a result of the drug suppressing basic cognitive functions at heavy doses, such as comprehension, memory, and reasoning skills.
*'''[[Effect::Motivation suppression]]''' - Due to flunitrazepam's heavy sedation and lethargy, doing any type of activity that requires moving, or high amounts of effort may be difficult to do on this compound, especially at higher doses.
*'''[[Effect::Motivation suppression]]''' - Due to flunitrazepam's heavy sedation and lethargy, doing any type of activity that requires moving, or high amounts of effort may be difficult to do on this compound, especially at higher doses.
*'''[[Effect::Language suppression]]''' - Flunitrazepam is known to cause slurred speech and difficulty communicating words in a clear fashion.
*'''[[Effect::Language suppression]]''' - Flunitrazepam causes slurred speech and difficulty communicating words in a clear or coherent fashion.
*'''[[Effect::Dream potentiation]]''' - While most people report that benzodiazepines like flunitrazepam tend to result in states of dreamless sleep, the opposite effect has also been reported, and seems to be particularly prevalent when a user is experiencing withdrawal from GABAergic substances (with alcohol being one notable example). The cause for these differences remain unclear at this point in time.
*'''[[Effect::Dream potentiation]]''' - While most people report that benzodiazepines like flunitrazepam tend to result in states of dreamless sleep, the opposite effect has also been reported, and seems to be particularly prevalent when a user is experiencing withdrawal from GABAergic substances (with alcohol being one notable example). The cause for these differences remain unclear at this point in time.
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===Experience reports===
===Experience reports===
There are currently no anecdotal reports which describe the effects of this compound within our [[experience index]]. Additional experience reports can be found here:
There are currently {{#ask:[[Category:SUBSTANCE]][[Category:Experience]] | format=count}} experience reports which describe the effects of this substance in our [[experience index]].
*'''[[Volumetric liquid dosing]]''' - If one's benzodiazepines are in powder form, they are unlikely to weigh out accurately without the most expensive of scales due to their extreme potency. To avoid this, one can dissolve the benzodiazepine volumetrically into a solution and dose it accurately based upon the methodological instructions linked within this tutorial [[Volumetric liquid dosing|here]].
* [https://erowid.org/experiences/subs/exp_Pharms_Flunitrazepam.shtml: Flunitrazepam] <!-- Check the link to see if it exists -->
==Toxicity and harm potential==
==Toxicity and harm potential==
[[File:harmchart.png|thumb|right|300px|Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.<ref>Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644</ref>]]
[[File:harmchart.png|thumb|right|300px|Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.<ref>{{cite journal | vauthors=((Nutt, D.)), ((King, L. A.)), ((Saulsbury, W.)), ((Blakemore, C.)) | journal=The Lancet | title=Development of a rational scale to assess the harm of drugs of potential misuse | volume=369 | issue=9566 | pages=1047–1053 | date=24 March 2007 | url=https://www.sciencedirect.com/science/article/pii/S0140673607604644 | issn=0140-6736 | doi=10.1016/S0140-6736(07)60464-4}}</ref>]]
{{Further|Research chemicals#Toxicity and harm potential}}
{{Further|Research chemicals#Toxicity and harm potential}}
Flunitrazepam likely has a [[Toxicity::low toxicity]] relative to dose.<ref>Benzodiazepine metabolism: an analytical perspective (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614</ref> However, it is [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[opioids]]]].
Flunitrazepam likely has a [[Toxicity::low toxicity]] relative to dose.<ref name="Mandroili2008"/> However, it is [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[opioids]]]].
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
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===Lethal dosage===
===Lethal dosage===
The oral [[LD50|LD<sub>50</sub>]] (lethal dose in 50% of the population) of flunitrazepam is 1200 mg/kg in mice and 415 mg/kg in rats.
The oral [[LD50|LD<sub>50</sub>]] (lethal dose in 50% of the population) of flunitrazepam is 1200 mg/kg in mice and 415 mg/kg in rats.
Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing and may necessitate a gradual dose reduction. For more information on tapering from benzodiazepines in a controlled manner, please see [http://www.benzo.org.uk/manual/bzcha02.htm this guide].
Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing and may necessitate a gradual dose reduction. For more information on tapering from benzodiazepines in a controlled manner, please see [http://www.benzo.org.uk/manual/bzcha02.htm this guide].
[[Benzodiazepine#Discontinuation|Benzodiazepine discontinuation]] is notoriously difficult; it is potentially life-threatening for individuals regularly using to discontinue use without tapering their dose over a period of weeks. There is an increased risk of [[hypertension]], [[seizures]], and death.<ref>A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812</ref> Drugs which lower the seizure threshold such as [[tramadol]] should be avoided during withdrawal.
[[Benzodiazepine#Discontinuation|Benzodiazepine discontinuation]] is notoriously difficult; it is potentially life-threatening for individuals regularly using to discontinue use without tapering their dose over a period of weeks. There is an increased risk of [[hypertension]], [[seizures]], and death.<ref name="Lann2009"/> Drugs which lower the seizure threshold such as [[tramadol]] should be avoided during withdrawal.
Flunitrazepam presents cross-tolerance with [[Cross-tolerance::all [[benzodiazepines]]]], meaning that after its consumption, all benzodiazepines will have a reduced effect.
Flunitrazepam presents cross-tolerance with [[Cross-tolerance::all [[benzodiazepines]]]], meaning that after its consumption, all benzodiazepines will have a reduced effect.
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===Overdose===
===Overdose===
Benzodiazepine overdose may occur when a [[benzodiazepine]] is taken in large quantities or concurrently with other depressants. This is particularly dangerous with other GABAergic depressants such as [[barbiturate|barbiturates]] and [[alcohol]] since they work similarly, but bind to distinct allosteric sites on the GABA<sub>A</sub> receptor. Thus their effects potentiate one another. Benzodiazepines increase the frequency in which the chlorine ion pore opens on the GABA<sub>A</sub> receptor while barbiturates increase the duration in which they are open, meaning when both are consumed, the ion pore will open more frequently and stay open longer<ref>Barbiturates and benzodiazepine effects | https://www.ncbi.nlm.nih.gov/pubmed/2471436</ref>. Benzodiazepine overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly and appropriately.
Benzodiazepine overdose may occur when a [[benzodiazepine]] is taken in large quantities or concurrently with other depressants. This is particularly dangerous with other GABAergic depressants such as [[barbiturate|barbiturates]] and [[alcohol]] since they work similarly, but bind to distinct allosteric sites on the GABA<sub>A</sub> receptor. Thus their effects potentiate one another. Benzodiazepines increase the frequency in which the chlorine ion pore opens on the GABA<sub>A</sub> receptor while barbiturates increase the duration in which they are open, meaning when both are consumed, the ion pore will open more frequently and stay open longer<ref>{{cite journal | vauthors=((Twyman, R. E.)), ((Rogers, C. J.)), ((Macdonald, R. L.)) | journal=Annals of Neurology | title=Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital | volume=25 | issue=3 | pages=213–220 | date= March 1989 | issn=0364-5134 | doi=10.1002/ana.410250302}}</ref>. Benzodiazepine overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly and appropriately.
Symptoms of a benzodiazepine overdose may include severe [[thought deceleration]], [[language suppression |slurred speech]], [[confusion]], [[delusions]], [[respiratory depression]], coma or death. Benzodiazepine overdoses may be treated effectively in a hospital environment, with generally favorable outcomes. Benzodiazepine overdoses are sometimes treated with [[flumazenil]], a GABA<sub>A</sub> antagonist<ref>Flumazenil, a benzodiazepine antagonist | https://www.ncbi.nlm.nih.gov/pubmed/8306565</ref>. However, care is primarily supportive in nature.
Symptoms of a benzodiazepine overdose may include severe [[thought deceleration]], [[language suppression |slurred speech]], [[confusion]], [[delusions]], [[respiratory depression]], coma or death. Benzodiazepine overdoses may be treated effectively in a hospital environment, with generally favorable outcomes. Benzodiazepine overdoses are sometimes treated with [[flumazenil]], a GABA<sub>A</sub> antagonist<ref>{{cite journal | vauthors=((Hoffman, E. J.)), ((Warren, E. W.)) | journal=Clinical Pharmacy | title=Flumazenil: a benzodiazepine antagonist | volume=12 | issue=9 | pages=641–656; quiz 699–701 | date= September 1993 | issn=0278-2677}}</ref>. However, care is primarily supportive in nature.
==Legal status==
==Legal status==
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*'''International''': Flunitrazepam is a Schedule III drug under the international Convention on Psychotropic Substances of 1971. {{citation needed}}
*'''International''': Flunitrazepam is a Schedule III drug under the international Convention on Psychotropic Substances of 1971. {{citation needed}}
*'''Australia''': Flunitrazepam is a Schedule 8 (S8) or controlled drug.{{citation needed}}
*'''Australia''': Flunitrazepam is a Schedule 8 (S8) or controlled drug.{{citation needed}}
*'''Austria:''' Flunitrazepam is legal for medical use and illegal when sold or possessed without a prescription under the AMG (Arzneimittelgesetz Österreich).{{citation needed}}
*'''Austria:''' Flunitrazepam is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich).{{citation needed}}
*'''Canada''': Flunitrazepam is a Schedule I controlled substance and is available by prescription only. {{citation needed}}
*'''Canada''': Flunitrazepam is a Schedule I controlled substance and is available by prescription only. {{citation needed}}
*'''Germany''': Since November 2011, flunitrazepam is controlled under Anlage 3 of the BtMG and requires a special prescription. {{citation needed}}
*'''Germany''': Since November 2011, flunitrazepam is controlled under Anlage 3 of the BtMG and requires a special prescription. {{citation needed}}
*'''Switzerland''': Flunitrazepam is listed as a controlled narcotic substance, but it is also sparesly prescribed as a sleep aid in major cases. Flunitrazolam tablets only come in 1mg dosage and are dyed green and blue which colors one's mouth notably when ingested in a dissolved beverage.<ref>https://fedlex.data.admin.ch/filestore/fedlex.data.admin.ch/eli/cc/2011/363/20161201/de/pdf-a/fedlex-data-admin-ch-eli-cc-2011-363-20161201-de-pdf-a.pdf</ref>
*'''United Kingdom''': Flunitrazepam is a Class C, Schedule 4 controlled drug under the Misuse of Drugs Regulations 2001.<ref>List of drugs currently controlled under the misuse of drugs legislation| https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/164222/controlled-drugs-list.pdf</ref> {{citation needed}}
*'''United Kingdom''': Flunitrazepam is a Class C, Schedule 4 controlled drug under the Misuse of Drugs Regulations 2001.<ref>List of drugs currently controlled under the misuse of drugs legislation| https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/164222/controlled-drugs-list.pdf</ref> {{citation needed}}
*'''United States''': Flunitrazepam is a Schedule IV drug under the Controlled Substances Act in the U.S but is not medically used. {{citation needed}}
*'''United States''': Flunitrazepam is a Schedule IV drug under the Controlled Substances Act in the U.S but is not medically used. {{citation needed}}
==Preparation methods==
*'''[[Volumetric liquid dosing]]''' - If one's benzodiazepines are in powder form, they are unlikely to weigh out accurately without the most expensive of scales due to their extreme potency. To avoid this, one can dissolve the benzodiazepine volumetrically into a solution and dose it accurately based upon the methodological instructions linked within this tutorial [[Volumetric liquid dosing|here]].
It may contain incorrect information, particularly with respect to dosage, duration, subjective effects, toxicity and other risks. It may also not meet PW style and grammar standards.
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
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Flunitrazepam was first synthesized in 1972 by Hoffmann-La Roche. It is used for the short term treatment of insomnia and as a preoperative sedative in some countries. It is approximately 10 times more potent by weight than diazepam.
Users should note that the sudden discontinuation of benzodiazepines can be potentially dangerous or life-threatening for individuals using regularly for extended periods of time, sometimes resulting in seizures or death.[3] It is highly recommended to taper one's dose by gradually lowering the amount taken each day for a prolonged period of time instead of stopping abruptly.[4]
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Flunitrazepam was discovered at Roche as part of the benzodiazepine work led by Leo Sternbach. It was first marketed in 1974 and entered the commerical market in Europe in 1975 under the name Rohypnol. In the 1980's it began to be available in other countries. [5]
It may be better known as the date-rape drug Rohypnol (with the street name “roofie”). In 1998, due to the abuse of the drug and recreation, Roche modified their 1 mg tablets to make them less soluble and added a blue dye for easier detection in drinks. [6]
In studies in Sweden, flunitrazepam was the second most common drug used in suicides, being found in about 16% of cases. In a retrospective Swedish study of 1587 deaths, in 159 cases benzodiazepines were found. In suicides when benzodiazepines were implicated, the benzodiazepines flunitrazepam and nitrazepam were occurring in significantly higher concentrations, compared to natural deaths. [5]
Chemistry
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).[7]
Pharmacology
Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter gamma aminobutyric acid (GABA) by acting on its receptors.[8] As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming effects) of Flunitrazepam on the nervous system.
The anticonvulsant properties of benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.[9]
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). This effect could be particularly dangerous, if flunitrazepam is used to aid in the commission of sexual assault, because victims may be unable to clearly recall the assault, the assailant, or the events surrounding the assault. [5]
80% of the flunitrazepam that is taken orally is absorbed but the bioavailability in suppository form is closer to 50%. [5]
Subjective effects
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWikicontributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
The general head space of flunitrazepam is described as one of intense sedation, sleepiness, relaxation, anxiety suppression, memory suppression and decreased inhibition similar to the headspace of higher doses of diazepam and temazepam.
Physical effects
Sedation - Flunitrazepam can produce extreme sedation and often results in an overwhelmingly lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness.
Perception of bodily heaviness - Flunitrazepam is known to cause feelings of heaviness in the body. This effect can range from motor impairment and difficulty moving at lower doses to complete lethargy or inability to stand up or move at high doses.
Paradoxical reactions to benzodiazepines such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%).[10][11]
These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.[12][13]
Cognitive effects
The cognitive effects of flunitrazepam can be broken down into several components which progressively intensify proportional to dosage. It contains a large number of typical depressant cognitive effects.
The most prominent of these cognitive effects generally include:
Amnesia - Flunitrazolam can cause considerable anmesia.
Emotion suppression - Although this compound primarily suppresses anxiety, it also dulls other emotions in a manner which is distinct but less intensive than that of antipsychotics.
Delusions of sobriety - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others. It most commonly occurs at heavy dosages.
Confusion - At heavy doses, flunitrazepam can cause confusion. This effect is a result of the drug suppressing basic cognitive functions at heavy doses, such as comprehension, memory, and reasoning skills.
Motivation suppression - Due to flunitrazepam's heavy sedation and lethargy, doing any type of activity that requires moving, or high amounts of effort may be difficult to do on this compound, especially at higher doses.
Language suppression - Flunitrazepam causes slurred speech and difficulty communicating words in a clear or coherent fashion.
Dream potentiation - While most people report that benzodiazepines like flunitrazepam tend to result in states of dreamless sleep, the opposite effect has also been reported, and seems to be particularly prevalent when a user is experiencing withdrawal from GABAergic substances (with alcohol being one notable example). The cause for these differences remain unclear at this point in time.
After effects
Rebound anxiety - Rebound anxiety is a commonly observed effect with anxiety relieving substances like benzodiazepines. It typically corresponds to the total duration spent under the substance's influence along with the total amount consumed in a given period, an effect which can easily lend itself to cycles of dependence and addiction.
Residual sleepiness - While benzodiazepines can be used as an effective sleep-inducing aid, their effects may persist into the morning afterward, which may lead users to feeling "groggy" or "dull" for up to a few hours.
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Volumetric liquid dosing - If one's benzodiazepines are in powder form, they are unlikely to weigh out accurately without the most expensive of scales due to their extreme potency. To avoid this, one can dissolve the benzodiazepine volumetrically into a solution and dose it accurately based upon the methodological instructions linked within this tutorial here.
Toxicity and harm potential
Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.[14]
Flunitrazepam likely has a low toxicity relative to dose.[2] However, it is [[Toxicity::potentially lethal when mixed with depressants like alcohol or opioids]].
The oral LD50 (lethal dose in 50% of the population) of flunitrazepam is 1200 mg/kg in mice and 415 mg/kg in rats.
Tolerance and addiction potential
Flunitrazepam is extremely physically and psychologically addictive.
Tolerance will develop to the sedative-hypnotic effects within a couple of days of continuous use. After cessation, the tolerance returns to baseline in 7 - 14 days. However, in certain cases, this may take significantly longer in a manner which is proportional to the duration and intensity of one's long-term usage.
Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing and may necessitate a gradual dose reduction. For more information on tapering from benzodiazepines in a controlled manner, please see this guide.
Benzodiazepine discontinuation is notoriously difficult; it is potentially life-threatening for individuals regularly using to discontinue use without tapering their dose over a period of weeks. There is an increased risk of hypertension, seizures, and death.[3] Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.
Flunitrazepam presents cross-tolerance with [[Cross-tolerance::all benzodiazepines]], meaning that after its consumption, all benzodiazepines will have a reduced effect.
Dangerous interactions
Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in small doses of each but still, increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.
Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
Stimulants - It is dangerous to combine benzodiazepines with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of benzodiazepines, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of benzodiazepines will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only dosing a certain amount of benzodiazepines per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.
Overdose
Benzodiazepine overdose may occur when a benzodiazepine is taken in large quantities or concurrently with other depressants. This is particularly dangerous with other GABAergic depressants such as barbiturates and alcohol since they work similarly, but bind to distinct allosteric sites on the GABAA receptor. Thus their effects potentiate one another. Benzodiazepines increase the frequency in which the chlorine ion pore opens on the GABAA receptor while barbiturates increase the duration in which they are open, meaning when both are consumed, the ion pore will open more frequently and stay open longer[15]. Benzodiazepine overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly and appropriately.
Symptoms of a benzodiazepine overdose may include severe thought deceleration, slurred speech, confusion, delusions, respiratory depression, coma or death. Benzodiazepine overdoses may be treated effectively in a hospital environment, with generally favorable outcomes. Benzodiazepine overdoses are sometimes treated with flumazenil, a GABAA antagonist[16]. However, care is primarily supportive in nature.
As such, it may contain incomplete or wrong information. You can help by expanding it.
International: Flunitrazepam is a Schedule III drug under the international Convention on Psychotropic Substances of 1971. [citation needed]
Australia: Flunitrazepam is a Schedule 8 (S8) or controlled drug.[citation needed]
Austria: Flunitrazepam is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich).[citation needed]
Canada: Flunitrazepam is a Schedule I controlled substance and is available by prescription only. [citation needed]
Germany: Since November 2011, flunitrazepam is controlled under Anlage 3 of the BtMG and requires a special prescription. [citation needed]
Switzerland: Flunitrazepam is listed as a controlled narcotic substance, but it is also sparesly prescribed as a sleep aid in major cases. Flunitrazolam tablets only come in 1mg dosage and are dyed green and blue which colors one's mouth notably when ingested in a dissolved beverage.[17]
United Kingdom: Flunitrazepam is a Class C, Schedule 4 controlled drug under the Misuse of Drugs Regulations 2001.[18][citation needed]
United States: Flunitrazepam is a Schedule IV drug under the Controlled Substances Act in the U.S but is not medically used. [citation needed]
↑ 2.02.1Mandrioli, R., Mercolini, L., Raggi, M. A. (October 2008). "Benzodiazepine metabolism: an analytical perspective". Current Drug Metabolism. 9 (8): 827–844. doi:10.2174/138920008786049258. ISSN1389-2002.
↑ 3.03.1Lann, M. A., Molina, D. K. (June 2009). "A fatal case of benzodiazepine withdrawal". The American Journal of Forensic Medicine and Pathology. 30 (2): 177–179. doi:10.1097/PAF.0b013e3181875aa0. ISSN1533-404X.
↑McLean, M. J., Macdonald, R. L. (February 1988). "Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture". The Journal of Pharmacology and Experimental Therapeutics. 244 (2): 789–795. ISSN0022-3565.
↑Saïas, T., Gallarda, T. (September 2008). "[Paradoxical aggressive reactions to benzodiazepine use: a review]". L’Encephale. 34 (4): 330–336. doi:10.1016/j.encep.2007.05.005. ISSN0013-7006.
↑Drummer, O. H. (February 2002). "Benzodiazepines - Effects on Human Performance and Behavior". Forensic Science Review. 14 (1–2): 1–14. ISSN1042-7201.
↑Twyman, R. E., Rogers, C. J., Macdonald, R. L. (March 1989). "Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital". Annals of Neurology. 25 (3): 213–220. doi:10.1002/ana.410250302. ISSN0364-5134.
↑Hoffman, E. J., Warren, E. W. (September 1993). "Flumazenil: a benzodiazepine antagonist". Clinical Pharmacy. 12 (9): 641–656; quiz 699–701. ISSN0278-2677.
