Flunitrazolam
Fatal overdose may occur when benzodiazepines are combined with other depressants such as opiates, barbiturates, gabapentinoids, thienodiazepines, alcohol or other GABAergic substances.[1]
It is strongly discouraged to combine these substances, particularly in common to heavy doses.
| Summary sheet: Flunitrazolam |
| Flunitrazolam | |||||||||||||||||||||||||||||||
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| Chemical Nomenclature | |||||||||||||||||||||||||||||||
| Common names | Flunitrazolam | ||||||||||||||||||||||||||||||
| Substitutive name | Flunitrazolam | ||||||||||||||||||||||||||||||
| Systematic name | 1-methyl-8-nitro-6-(2-fluorophenyl)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine | ||||||||||||||||||||||||||||||
| Class Membership | |||||||||||||||||||||||||||||||
| Psychoactive class | Depressant | ||||||||||||||||||||||||||||||
| Chemical class | Benzodiazepine | ||||||||||||||||||||||||||||||
| Routes of Administration | |||||||||||||||||||||||||||||||
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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.
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. 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.
Chemistry
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This chemistry section is incomplete. You can help by adding to it. |
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 PsychonautWiki contributors. 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 
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- 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.
- Respiratory depression
- Dizziness
- Muscle relaxation - Muscle relaxation can be quite pronounced
- 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 
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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 
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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.
- Anxiety suppression
- Thought deceleration
- Analysis suppression
- Disinhibition
- Information processing suppression
- Compulsive redosing
- 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 
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- 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.
- Dream potentiation or Dream suppression
- 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.
- Thought deceleration
- Thought disorganization
- Irritability
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:
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 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
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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. |
Flunitrazolam likely has a low toxicity relative to dose.[14] However, it is potentially lethal when mixed with depressants like alcohol or opioids.
It is strongly recommended that one use harm reduction practices when using this substance.
Dependence and abuse potential
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 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.
Legal status
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This legality section is a stub. 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]
See also
External links
References
- ↑ Risks of Combining Depressants - TripSit
- ↑ 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
. PMID 29462316.
- ↑ "Europol 2016 Annual Report on the implementation of Council Decision 2005/387/JHA" (PDF).
- ↑ 4.0 4.1 Lann, 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. ISSN 1533-404X.
- ↑ Kahan, M., Wilson, L., Mailis-Gagnon, A., Srivastava, A. (November 2011). "Canadian guideline for safe and effective use of opioids for chronic noncancer pain. Appendix B-6: Benzodiazepine Tapering". Canadian Family Physician. 57 (11): 1269–1276. ISSN 0008-350X.
- ↑ Haefely, W. (29 June 1984). "Benzodiazepine interactions with GABA receptors". Neuroscience Letters. 47 (3): 201–206. doi:10.1016/0304-3940(84)90514-7. ISSN 0304-3940.
- ↑ 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. ISSN 0022-3565.
- ↑ 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. ISSN 1945-2403.
- ↑ 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. ISSN 0013-7006.
- ↑ Paton, C. (December 2002). "Benzodiazepines and disinhibition: a review". Psychiatric Bulletin. 26 (12): 460–462. doi:10.1192/pb.26.12.460. ISSN 0955-6036.
- ↑ Bond, A. J. (1 January 1998). "Drug- Induced Behavioural Disinhibition". CNS Drugs. 9 (1): 41–57. doi:10.2165/00023210-199809010-00005. ISSN 1179-1934.
- ↑ Drummer, O. H. (February 2002). "Benzodiazepines - Effects on Human Performance and Behavior". Forensic Science Review. 14 (1–2): 1–14. ISSN 1042-7201.
- ↑ Nutt, D., King, L. A., Saulsbury, W., Blakemore, C. (24 March 2007). "Development of a rational scale to assess the harm of drugs of potential misuse". The Lancet. 369 (9566): 1047–1053. doi:10.1016/S0140-6736(07)60464-4. ISSN 0140-6736.
- ↑ 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. ISSN 1389-2002.
- ↑ Twyman, R. E., Rogers, C. J., Macdonald, R. L. (March 1989). "Differential regulation of γ-aminobutyric acid receptor channels by diazepam and phenobarbital". Annals of Neurology. 25 (3): 213–220. doi:10.1002/ana.410250302. ISSN 0364-5134.
- ↑ Hoffman, E. J., Warren, E. W. (September 1993). "Flumazenil: a benzodiazepine antagonist". Clinical Pharmacy. 12 (9): 641–656; quiz 699–701. ISSN 0278-2677.
- ↑ 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