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'''Flunitrazolam''' is a novel lesser-known [[psychoactive class::depressant]] substance of the [[chemical class::benzodiazepine]] class. It has been noted for its unusual potency for a benzodiazepine compound, being active in the low microgram range. This trait is also shared by compounds such as [[flubromazolam]] and [[clonazolam]]. Similar to flubromazolam, this is an ultra potent benzodiazepine. A dose of about 0.1 mg (100 µg) is equivalent to 10 mg diazepam or 0.25 mg alprazolam.<ref name="pmid29462316">{{cite journal | vauthors = Ameline A, Richeval C, Gaulier JM, Raul JS, Kintz P | title = Characterization of Flunitrazolam, a New Designer Benzodiazepine, in Oral Fluid After a Controlled Single Administration | journal = Journal of Analytical Toxicology | volume = 42 | issue = 6 | pages = e58–e60 | date = July 2018 | pmid = 29462316 | doi = 10.1093/jat/bky012 | doi-access = free }}</ref>
'''Flunitrazolam''' is a novel synthetic [[psychoactive class::depressant]] substance of the [[chemical class::benzodiazepine]] class which produces [[anxiolytic]], [[disinhibition|disinhibiting]], [[sedative]], [[muscle relaxant]], and [[memory suppression|memory suppressing]] effects when [[route of administration|administered]]. It has been noted for its unusual potency for a benzodiazepine compound, being active in the microgram range. This trait is also shared by compounds such as [[flubromazolam]] and [[clonazolam]].
Flunitrazolam first appeared on the online [[research chemical]] market in 2016.<ref>{{cite web | url = https://www.europol.europa.eu/sites/default/files/documents/tdan17001enn_pdfweb.pdf | title = Europol 2016 Annual Report on the implementation of Council Decision 2005/387/JHA }}</ref> It appeared in the form of pressed pellets and was offered alongside other novel benzodiazepines such as [[clonazolam]] and [[flubromazolam]]. Of these, it appears to be entirely novel and has no precedent in the scientific literature before being made available for sale on online.
Flunitrazolam first appeared on the [[research chemicals]] market in 2016.{{citation needed}} It typically appeared in the form of pressed pellets along with other novel benzodiazepines such as [[flunitrazepam]] and [[flubromazolam]]. Of these, this compound is entirely novel and has no precedent in the scientific literature before being made available on online. As a result, information regarding dosage, effects, and toxicity should be regarded with caution. Any comments regarding its pharmacology are purely speculation based upon the subjective effects it induces and its structural similarity to [[triazolam]], [[pyrazolam]] and other benzodiazepines.
Information regarding dosage, effects, and toxicity should be regarded with caution. Any comments regarding its pharmacology are purely speculation based upon the subjective effects it induces and its structural similarity to [[funitrazolam]] and other benzodiazepines, with very little research done for far with this particular compound.
It is 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 usage 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>
[[Subjective effects]] include [[sedation]], [[anxiety suppression]], [[muscle relaxation]], [[disinhibition]], and [[memory suppression]]. Some users have reported [[seizures]] on high doses of this compound, without any contributing cause or withdrawal that might have triggered this. Only [[r05-4864]] has this property, although to a greater extent.
Very little data exists about the pharmacological properties, metabolism, and toxicity of flunitrazolam in humans. It has no history of human usage until 2016 when it began being sold as a gray-area research chemical by online vendors. Due to the high dependence-forming and addiction potential that this substance shares with other members of the [[benzodiazepine]] class, as well as its [[alcohol]]-like ability to induce dangerous [[disinhibition|disinhibitory]] [[amnesia|black-out]] states, it is highly advised to use proper [[harm reduction practices]] if choosing to use this substance, especially concurrently with other depressants.
Very little data exists about the pharmacological properties, metabolism, and toxicity of flunitrazolam in humans. Preliminary reports suggest it has high abuse potential similar to that of other potent benzodiazepines. It likely produces physical dependence with chronic use. Additionally, dosing is a concern, as potent benzodiazepines can cause long-lasting blackouts with minor dosing miscalculations.
It is 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 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 usage 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>
It is highly advised to use harm reduction practices if using this substance.
==Chemistry==
==Chemistry==
{{chemistry}}
{{chemistry}}
Flunitrazolam is a chemical of the benzodiazepine class. Flunitrazolam is named for the fluorine, bromine, and triazole substitutions on its core benzodiazepine skeleton (FLUorine-NITro-AZOLe-AM). Flunitrazolam is a member of the benzodiazepine class as it contains a 1,4 diazepine ring fused to a substituted benzene ring. Bromine is bound to this bicyclic structure at R<sub>7</sub>. Additionally, a fluorine substituted phenyl ring is bound to this structure at R<sub>5</sub>.
Flunitrazolam is a chemical of the benzodiazepine class. Flunitrazolam is named for the fluorine, bromine, and triazole substitutions on its core benzodiazepine skeleton (FLUorine-NITRo-AZOLe-AM). Flunitrazolam is a member of the benzodiazepine class as it contains a 1,4 diazepine ring fused to a substituted benzene ring. Bromine is bound to this bicyclic structure at R<sub>7</sub>. Additionally, a fluorine substituted phenyl ring is bound to this structure at R<sub>5</sub>.
Flunitrazolam also contains a methylated triazole ring fused to and incorporating R<sub>1</sub> and R<sub>2</sub> of its diazepine ring. Flunitrazolam belongs to a class of benzodiazepines containing this fused triazole ring, called triazolobenzodiazepines, distinguished by the suffix "-zolam".
Flunitrazolam also contains a methylated triazole ring fused to and incorporating R<sub>1</sub> and R<sub>2</sub> of its diazepine ring. Flunitrazolam belongs to a class of benzodiazepines containing this fused triazole ring, called triazolobenzodiazepines, distinguished by the suffix "-zolam".
==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 flunitrazolam 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 flunitrazolam 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>{{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>
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>
Experimental results for Flunitrazolam often yield findings of sedation, disinhibition, dream potentiation, residual sleepiness, thought deceleration, and muscle relaxation.<ref>{{cite journal | vauthors=((Ameline, A.)), ((Richeval, C.)), ((Gaulier, J.-M.)), ((Raul, J.-S.)), ((Kintz, P.)) | journal=Journal of Analytical Toxicology | title=Characterization of Flunitrazolam, a New Designer Benzodiazepine, in Oral Fluid After a Controlled Single Administration | volume=42 | issue=6 | pages=e58–e60 | date=1 July 2018 | issn=1945-2403 | doi=10.1093/jat/bky012}}</ref>
==Subjective effects==
==Subjective effects==
Flunitrazolam has distinct effects which range from barely noticeable to complete memory loss, depending strongly on dosage and physical differences in metabolism. It shares some common traits among many users, including mild or threshold effects at lower dosage levels before quickly turning into very amnesic or black-out states over a certain dosage (some people report 300 mg). It predominantly has hypnotic effects and notable muscle relaxation, while lacking anxiety suppression or sedating effects.
{{Preamble/SubjectiveEffects}}
{{Preamble/SubjectiveEffects}}
{{effects/base
{{effects/base
|{{effects/physical|
|{{effects/physical|
*'''[[Effect::Sedation]]''' - In terms of energy level alterations, this drug 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]]''' - In terms of energy level alterations, this drug 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::Motor control loss]]'''
*'''[[Effect::Motor control loss]]''' - This only becomes apparant at the higher dosage range.
*'''[[Effect::Respiratory depression]]'''
*'''[[Effect::Respiratory depression]]'''
*'''[[Effect::Dizziness]]'''
*'''[[Effect::Dizziness]]'''
*'''[[Effect::Muscle relaxation]]
*'''[[Effect::Muscle relaxation]]''' - Muscle relaxation can be quite pronounced
*'''[[Effect::Seizure]]''' - High to very high dosages of Flunitrazolam have reportedly caused seizures in people without any additional triggers such as [[withdrawal]]. It is not normal for a benzodiazepine to produce this effect, so one should generally avoid heavy dosages.
}}
}}
{{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><p>
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><p>
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></p>
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></p>
}}
}}
|{{effects/cognitive|
|{{effects/cognitive|
The cognitive effects of flunitrazolam can be broken down into several components which progressively intensify proportional to dosage. The general head space of flunitrazolam is described by many as one of intense sedation and decreased inhibition.
The cognitive effects of flunitrazolam can be broken down into several components which progressively intensify proportional to dosage. The general head space of flunitrazolam is described by many as one of intense sedation and decreased inhibition.
*'''[[Effect::Amnesia]]'''
*'''[[Effect::Amnesia]]''' - Past a certain dosage level Flunitrazolam can suddenly become completely amnesic.
*'''[[Effect::Emotionality suppression]]''' - Although this compound primarily suppresses anxiety, it also dulls other emotions in a manner which is distinct but less intensive than that of [[antipsychotic|antipsychotics]].
*'''[[Effect::Emotionality suppression]]''' - Although this compound primarily suppresses anxiety, it also dulls other emotions in a manner which is distinct but less intensive than that of [[antipsychotic|antipsychotics]].
*'''[[Effect::Delusions|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.
*'''[[Effect::Delusions|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.
*'''[[Effect::Sleepiness]]'''
*'''[[Effect::Sleepiness]]''' - Flunitrazolam has very pronounced hypnotic effects.
}}
}}
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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 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 instructions linked within this [[Volumetric liquid dosing|tutorial]].
*'''[[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 instructions linked within this [[Volumetric liquid dosing|tutorial]].
Due to Flunitrazolam's extreme potency compared to even other ultrapotent benzodiazepines it should be used even more carefully when making and using a volumetric liquid solution. One should weigh at least 30mgs or Flunitrazolam which requires a bit bigger dropper bottles. The bottle should be shaked everytime before usage.
==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>]]
{{toxicity}}
[[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}}
Flunitrazolam 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]]]].
Flunitrazolam likely has a [[Toxicity::low toxicity]] relative to dose.<ref>{{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> 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 substance.
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this substance.
===Tolerance and addiction potential===
===Dependence and abuse potential===
Flunitrazolam is [[Addiction potential::extremely physically and psychologically addictive]].
Flunitrazolam is [[Addiction potential::extremely physically and psychologically addictive]].
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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 using regularly 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 using regularly 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.
Flunitrazolam presents cross-tolerance with [[Cross-tolerance::all [[benzodiazepines]]]], meaning that after its consumption all benzodiazepines will have a reduced effect.
Flunitrazolam presents cross-tolerance with [[Cross-tolerance::all [[benzodiazepines]]]], meaning that after its consumption all benzodiazepines will have a reduced effect.
===Overdose===
===Overdose===
Benzodiazepine overdose may occur when a [[benzodiazepine]] is taken in extremely heavy quantities or concurrently with other [[depressants]]. This is particularly dangerous with other GABAergic depressants such as [[barbiturate|barbiturates]] and [[alcohol]] since they work in a similar fashion, 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>Twyman, R. E., Rogers, C. J., & Macdonald, R. L. (1989). Differential regulation of γ‐aminobutyric acid receptor channels by diazepam and phenobarbital. ''Annals of Neurology'', 25(3), 213-220. https://doi.org/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 properly.
Benzodiazepine overdose may occur when a [[benzodiazepine]] is taken in extremely heavy quantities or concurrently with other [[depressants]]. This is particularly dangerous with other GABAergic depressants such as [[barbiturate|barbiturates]] and [[alcohol]] since they work in a similar fashion, 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 γ-aminobutyric acid receptor channels by diazepam and phenobarbital | volume=25 | issue=3 | pages=213–220 | date= March 1989 | url=https://onlinelibrary.wiley.com/doi/10.1002/ana.410250302 | issn=0364-5134 | doi=10.1002/ana.410250302}}</ref>.
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>Amrein, R., Leishman, B., Bentzinger, C., & Roncari, G. (1987). Flumazenil in benzodiazepine antagonism. ''Medical Toxicology and Adverse Drug Experience'', 2(6), 411-429. PMID: 8306565</ref> however care is primarily supportive in nature.
Benzodiazepine overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly and properly.
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.
===Dangerous interactions===
===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 low doses of each but still increase the potential risk of death. [https://www.google.com/ Independent research] should always be done to ensure that a combination of two or more substances is safe before consumption.
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 low doses of each but still increase the potential risk of death. [https://www.google.com/ Independent research] should always be done to ensure that a combination of two or more substances is safe before consumption.
*'''[[Depressants]]''' (''[[1,4-Butanediol]], [[2-methyl-2-butanol]], [[alcohol]], [[barbiturates]], [[GHB]]/[[GBL]], [[methaqualone]], [[opioids]]'') - This combination can result in dangerous or even fatal levels of [[respiratory depression]]. These substances potentiate the [[muscle relaxation]], [[sedation]] and [[amnesia]] caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation ("pulmonary aspiration"). If extreme sleepiness or loss of consciousness occur, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it.
*'''[[Depressants]]''' (''[[1,4-Butanediol]], [[2-methyl-2-butanol]], [[alcohol]], [[barbiturates]], [[GHB]]/[[GBL]], [[methaqualone]], [[opioids]]'') - This combination can result in dangerous or even fatal levels of [[respiratory depression]]. These substances potentiate the [[muscle relaxation]], [[sedation]] and [[amnesia]] caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation ("pulmonary aspiration"). If extreme sleepiness or loss of consciousness occur, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it.
*'''[[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.
*'''[[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.
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{{legalStub}}
{{legalStub}}
Flunitrazolam is currently a gray area compound within most (if not all) parts of the world. This means that it is not known to be specifically illegal within any country, but people may still be charged for its possession under certain circumstances such as under analogue laws and with intent to sell or consume.
Flunitrazolam is currently a gray area compound within most (if not all) parts of the world. This means that it is not known to be specifically illegal within any country, but people may still be charged for its possession under certain circumstances such as under analogue laws and with intent to sell or consume.
*'''Switzerland:''' Flunitrazolam is legal in Switzerland as of September 2021.<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>
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Flunitrazolam is a novel lesser-known depressant substance of the benzodiazepine class. It has been noted for its unusual potency for a benzodiazepine compound, being active in the low microgram range. This trait is also shared by compounds such as flubromazolam and clonazolam. Similar to flubromazolam, this is an ultra potent benzodiazepine. A dose of about 0.1 mg (100 µg) is equivalent to 10 mg diazepam or 0.25 mg alprazolam.[2]
Flunitrazolam first appeared on the online research chemical market in 2016.[3] It appeared in the form of pressed pellets and was offered alongside other novel benzodiazepines such as clonazolam and flubromazolam. Of these, it appears to be entirely novel and has no precedent in the scientific literature before being made available for sale on online.
Information regarding dosage, effects, and toxicity should be regarded with caution. Any comments regarding its pharmacology are purely speculation based upon the subjective effects it induces and its structural similarity to funitrazolam and other benzodiazepines, with very little research done for far with this particular compound.
Very little data exists about the pharmacological properties, metabolism, and toxicity of flunitrazolam in humans. Preliminary reports suggest it has high abuse potential similar to that of other potent benzodiazepines. It likely produces physical dependence with chronic use. Additionally, dosing is a concern, as potent benzodiazepines can cause long-lasting blackouts with minor dosing miscalculations.
It is worth noting 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.[4] 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 usage abruptly.[5]
It is highly advised to use harm reduction practices if using this substance.
Flunitrazolam is a chemical of the benzodiazepine class. Flunitrazolam is named for the fluorine, bromine, and triazole substitutions on its core benzodiazepine skeleton (FLUorine-NITRo-AZOLe-AM). Flunitrazolam is a member of the benzodiazepine class as it contains a 1,4 diazepine ring fused to a substituted benzene ring. Bromine is bound to this bicyclic structure at R7. Additionally, a fluorine substituted phenyl ring is bound to this structure at R5.
Flunitrazolam also contains a methylated triazole ring fused to and incorporating R1 and R2 of its diazepine ring. Flunitrazolam belongs to a class of benzodiazepines containing this fused triazole ring, called triazolobenzodiazepines, distinguished by the suffix "-zolam".
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.[6] As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming effects) of flunitrazolam 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.[7]
Experimental results for Flunitrazolam often yield findings of sedation, disinhibition, dream potentiation, residual sleepiness, thought deceleration, and muscle relaxation.[8]
Subjective effects
Flunitrazolam has distinct effects which range from barely noticeable to complete memory loss, depending strongly on dosage and physical differences in metabolism. It shares some common traits among many users, including mild or threshold effects at lower dosage levels before quickly turning into very amnesic or black-out states over a certain dosage (some people report 300 mg). It predominantly has hypnotic effects and notable muscle relaxation, while lacking anxiety suppression or sedating 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 ☠.
Physical effects
Sedation - In terms of energy level alterations, this drug 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.
Motor control loss - This only becomes apparant at the higher dosage range.
Seizure - High to very high dosages of Flunitrazolam have reportedly caused seizures in people without any additional triggers such as withdrawal. It is not normal for a benzodiazepine to produce this effect, so one should generally avoid heavy dosages.
Paradoxical effects
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%).[9][10]
These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.[11][12]
Cognitive effects
The cognitive effects of flunitrazolam can be broken down into several components which progressively intensify proportional to dosage. The general head space of flunitrazolam is described by many as one of intense sedation and decreased inhibition.
Amnesia - Past a certain dosage level Flunitrazolam can suddenly become completely amnesic.
Emotionality 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.
Sleepiness - Flunitrazolam has very pronounced hypnotic effects.
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 flunitrazolam can be used as an effective sleep-inducing aid, its effects may persist into the morning afterwards, which may lead users to feeling "groggy" or "dull" for a few hours if not significantly longer.
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 instructions linked within this tutorial.
Due to Flunitrazolam's extreme potency compared to even other ultrapotent benzodiazepines it should be used even more carefully when making and using a volumetric liquid solution. One should weigh at least 30mgs or Flunitrazolam which requires a bit bigger dropper bottles. The bottle should be shaked everytime before usage.
Toxicity and harm potential
This toxicity and harm potential section is a stub.
As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it. Note: Always conduct independent research and use harm reduction practices if using this substance.
Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.[13]
Flunitrazolam likely has a low toxicity relative to dose.[14] However, it is [[Toxicity::potentially lethal when mixed with depressants like alcohol or opioids]].
Flunitrazolam 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 using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of hypertension, seizures, and death.[4] Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.
Flunitrazolam presents cross-tolerance with [[Cross-tolerance::all benzodiazepines]], meaning that after its consumption all benzodiazepines will have a reduced effect.
Overdose
Benzodiazepine overdose may occur when a benzodiazepine is taken in extremely heavy quantities or concurrently with other depressants. This is particularly dangerous with other GABAergic depressants such as barbiturates and alcohol since they work in a similar fashion, 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 properly.
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.
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 low 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.
Depressants (1,4-Butanediol, 2-methyl-2-butanol, alcohol, barbiturates, GHB/GBL, methaqualone, opioids) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances potentiate the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation ("pulmonary aspiration"). If extreme sleepiness or loss of consciousness occur, users should attempt to fall asleep in the recovery position or have a friend move them into it.
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 mask 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.
As such, it may contain incomplete or wrong information. You can help by expanding it.
Flunitrazolam is currently a gray area compound within most (if not all) parts of the world. This means that it is not known to be specifically illegal within any country, but people may still be charged for its possession under certain circumstances such as under analogue laws and with intent to sell or consume.
Switzerland: Flunitrazolam is legal in Switzerland as of September 2021.[17]
↑Ameline A, Richeval C, Gaulier JM, Raul JS, Kintz P (July 2018). "Characterization of Flunitrazolam, a New Designer Benzodiazepine, in Oral Fluid After a Controlled Single Administration". Journal of Analytical Toxicology. 42 (6): e58–e60. doi:10.1093/jat/bky012. PMID29462316.
↑ 4.04.1Lann, 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.
↑Ameline, A., Richeval, C., Gaulier, J.-M., Raul, J.-S., Kintz, P. (1 July 2018). "Characterization of Flunitrazolam, a New Designer Benzodiazepine, in Oral Fluid After a Controlled Single Administration". Journal of Analytical Toxicology. 42 (6): e58–e60. doi:10.1093/jat/bky012. ISSN1945-2403.
↑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.
↑Mandrioli, 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.
↑Hoffman, E. J., Warren, E. W. (September 1993). "Flumazenil: a benzodiazepine antagonist". Clinical Pharmacy. 12 (9): 641–656; quiz 699–701. ISSN0278-2677.