Introduction to Flunitrazepam

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Flunitrazepam is a potent hypnotic of the benzodiazepine class. It is classified as a 7-nitro, long-acting benzodiazepine, with a considerable half-life of 18-26 hours. It is prescribed for severe insomnia, usually for insomniac patients who are resistant to less potent hypnotics such as temazepam or non-benzodiazepines such as zolpiclone. Due to issues of dependence and tolerance associated with all benzodiazepines, flunitrazepam is only used for the short-term management of insomnia.[2]

The most common form of flunitrazepam is the brand Rohypnol, owned by the Roche pharmaceutical company, and most countries have Rohypnol available in 1mg and 2mg tablets. The most common slang term for flunitrazepam tablets is "roofies", spread by the drug's appearance in popular culture, such as the comedy film "The Hangover". Flunitrazepam is commonly considered to be a "date-rape drug", used by rapists to incapacitate a victim, although this is in fact a common misconception (see below). The other most common brand name of flunitrazepam tablets is Hypnodorm.

Like all benzodiazepines, flunitrazepam is a controlled substance worldwide, and is only available with a prescription from a licensed professional.

Using Flunitrazepam

Ways of Administration

Flunitrazepam comes in 1mg or 2mg tablets. It's oral availability is moderately high, at 64-77%,[3] and swallowing is the most common route of administration. Oral effects 15-25 minutes after swallowing. While highly soluble in chloroform and glacial acetic acid, flunitrazepam does not dissolve well in either methanol or water. [4] Due to its insolubility in water, snorting flunitrazepam is not an effective way to take the drug. It will not dissolve, hardly at all, into the mucous membranes. However, some people snort flunitrazepam anyway. There have also been reports of people injecting flunitrazepam intravenously. At a 1mg dose, a flunitrazepam injection would cause severe sedation and amnesia, which may well be extremely dangerous to the user. Like diazepam, flunitrazepam causes pain at the injection site, and may cause phlebitis (inflammation of a vein). [5]

Effects of Flunitrazepam

The main effect of flunitrazepam is sedation. The user becomes extremely tired, will be inclined to sleep, and may fall asleep even if he or she didn't want to. The sedative effect of flunitrazepam may be euphoric for some users, although many people don't consider benzodiazepines to be euphoric drugs.

The other effects of flunitrazepam are:

• Hypnotic effects - make you sleepy, induces sleep.
• Anticonvulsant effects - if you are epileptic, flunitrazepam can prevent seizures, although it is not clinically approved for this indication, and is not a substitute for other anticonvulsant drugs you may be taking.
• Anxiolytic effects - Like most benzodiazepines, flunitrazepam reduces feelings of anxiety, stress, worry, fear and nervousness. Again, flunitrazepam is not approved for use as an anxiolytic because it is too sedating. Other benzodiazapines, such as alprazolam (Xanax) or lorazepam (Ativan), are better suited to treating anxiety disorders.
• Amnestic effects - Flunitrazepam causes anterograde amnesia, wherein you are likely to forget things you said, thought and did while you were under its influence. For this reason, flunitrazepam is best kept for use only at home, and you should go to bed as soon as flunitrazepam begins to make you feel tired. While in an amnesic state, people become confused, agitated, incoherent, and will sometimes become violent or have mood swings. These effects could lead to dangerous and/or embarrassing situations.
• Relaxtion of skeletal muscle - Flunitrazepam decreases muscle tone and reduces the efficacy of skeletal muscle. This means that flunitrazepam can make you stumble, fall (and possibly injure yourself), and your hands and fingers can become unsteady, so that you might drop things you are holding, be unable to type or use a pen properly, etc. If you suffer from spasms, flunitrazepam is likely to make them stop, but safer drugs are used for this condition.

Combinations with Flunitrazepam

Flunitrazepam is metabolized by the CYP3A4 liver enzyme, and combining flunitrazepam with a drug that inhibits this enzyme will lead to a larger amount of flunitrazepam in the blood plasma.[6] This could result in a fatal overdose. Taking flunitrazepam with a drug that induces this enzyme may reduce the effectiveness of flunitrazepam.

The drug is often combined with alcohol to increase the sedative and relaxing effect. The combined sedation of alcohol and flunitrazepam could easily lead to death by cardiac arrest or severe respiratory depression. Combining flunitrazepam with any other sedating drugs is also likely to be dangerous. These drugs include antipsychotics, tranquilizers, some antidepressants (particularly tricyclic ones such as trazodone), other hypnotics, opioids such as heroin, oxycodone, codeine, opium, morphine, etc., anti-epileptic drugs, sedative antihistamines, and other muscle relaxants such as calisoprodol or baclofen.

Flunitrazepam can be safely combined with cannabis, which may increase its hypnotic effects without extra bradycardia or respiratory depression.

It is perfectly safe to smoke cigarettes with flunitrazepam, although you should always avoid smoking in bed or around anything flammable under the influence of flunitrazepam, since you might become so sedated that you fall asleep with the cigarette/joint still lit, and burn your house down and get yourself killed.

Different Uses for Flunitrazepam

Flunitrazepam is best used for getting to sleep and relieving insomnia, and is one of the most effective drugs for inducing sleep around.

It can also be used for anxiety, although a doctor would never prescribe it for this condition. If you find yourself with extreme anxiety and flunitrazepam is all you have to relieve it, it may help to take 0.5mgs or even 0.25mgs of flunitrazepam. These doses can be approximated by cutting a 1mg tablet in half or in quarters. A full 1mg is more likely to "knock the user out" than relieve anxiety. This use of flunitrazepam would certainly be for exceptional, emergency-only situations. Because the drug is likely to cause amnesia, this would not be a good idea if you have to interact with people or have something important to do, since the drug may alter your behavior.

Flunitrazepam is also used for relieving withdrawal symptoms of other drugs, such as opioids, alcohol and stimulants like cocaine, amphetamine and crystal meth. It is of course effective for relieving insomnia, a common withdrawal symptom of many drugs, and eases the syndrome by "sleeping through" sections of it. Of course, it is unwise to treat the withdrawals of an addictive drug with another addictive drug like flunitrazepam.

Unfortunately, flunitrazepam is also used for date-rape, wherein a rapist spikes the drink of his intended victim, or uses some other way of drugging the victim, and will then rape the victim while he or she is unconscious. While flunitrazepam or "roofies" is the most well-known date-rape drug, one study by Robertson found that it is only used in 1% or date-rape cases; rapists tend to use soporific drugs that are easier to acquire than flunitrazepam, such as GHB.[7]
Another criminal use of flunitrazepam is in "drug-assisted robbery" where a victim is drugged by flunitrazepam into an unresponsive state and subsequently robbed.

Sadly, flunitrazepam is sometimes used for suicide, by deliberately taking an overdose.

Pharmacology of Flunitrazepam

As a benzodiazepine, flunitrazepam binds the BZD receptor, a subset of GABAA, increasing the affinity of the neurotransmitter GABA for this receptor. Therefore, while flunitrazepam is bound to a BZD receptor, GABA works with more efficacy, increasing the conduction of chloride ions through the cell membrane. A high enough number of chloride ions in a neuron will hyperpolarize it, and make it less likely to fire an action potential. Less neuronal firing reduces brain activity, and lessens feelings of anxiety, as well as inducing sleep. [8]

It undergoes phase one metabolism by the cytochrome P450 3A4 hepatic enzyme.

Chemistry of Flunitrazepam

Column 1	Column 2
Systematic(IUPAC) name:	5-(2-fluorophenyl)-1-methyl-7-nitro-1H-benzo[e][1,4]diazepin-2(3H)-one
Synonyms:	5-(2-fluorophenyl)-1-methyl-7-nitro-2,3-dihydro-1H-1,4-benzodiazepin-2-one, 5-(2-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one, 1-methyl-7-nitro-5-(2-fluorophenyl)-3H-1,4-benzodiazepin-2(1H)-one, Ro-5-4200, Narcozep, Rohypnol, Roipnol
Molecular Formula:	C16H12FN3O3
Molar mass:	313.28 g/mol [2]
CAS Registry Number:	1622-62-4
Melting Point:	166-167 °C (crystals from dichloromethane/hexane), also reported 170-172°C (crystals from acetonitrile/methanol
Boiling Point:	no data
Flash Point:	no data
Solubility:	Freely soluble in Chloroform & Glacial acetic acid; Slightly soluble in Methanol & Anhydrous ethanol; Practically insoluble in water
Additional data:	none
Notes:	Crystallized from dichloromethane/hexane or acetonitrile/methanol

[1]

Composition: carbon 61.34%, hydrogen 3.86%, fluoride 6.06%, nitrogen 13.41% and oxygen 15.3%.[9]

It is the fluorinated methylamino derivative of nitrazepam, another benzodiazepine hypnotic commonly used for insomnia, and nitrazepam is flunitrazepam's chemical precursor in flunitrazepam synthesis.

Forms of Flunitrazepam

Flunitrazepam comes in a variety of forms, depending on the country of origin. It comes in tablet form, typically in either a 1mg or 2mg dose. Some countries market ampoules of a flunitrazepam solution. Note that the name Rohypnol, though the spelling varies from country to country, is a trademark of Hoffman La Roche pharmaceuticals. The following is a list of different flunitrazepam brands in different countries.

• Argentina - Nervocuril, Primum, Rohypnol
• Australia - Hypnodorm
• Austria - Guttanotte; Rohypnol; Somnubene
• Belgium - Rohypnol
• Brazil - Rohydorm; Rohypnol
• Chile - Ipnopen
• Czech Republic - Rohypnol
• Denmark - Flunipam, Ronal
• France - Narcozep, Rohypnol
• Germany - Flunibeta, Fluninoc, Rohypnol
• Greece - Hipnosedon, Ilman, Neo Nifalium, Vulbegal
• Hong Kong - Flunita, Rohypnol
• Ireland - Rohypnol
• Israel - Hypnodorm
• Italy - Darkene, Roipno, Valsera
• Mexico - Rohypnol
• Netherland - Rohypnol
• Norway - Flunipam
• Portugal- Rohypnol; Sedex
• South Africa - Insom; Rohypnol
• Spain - Rohipnol
• Sweden - Fluscand
• Switzerland - Rohypnol
• Thailand - Rohypnol, Guttanotte, Rohypnol, Somnubene

The Dangers of Flunitrazepam

Like all benzodiazepines, flunitrazepam is addictive. Dependence to the drug develops after several consecutive days of use, and because of its rather long half-life, dependence can develop even if used every other day for a week to two week period. For this reason, flunitrazepam should not be used for any longer than 5 consecutive days.

The withdrawal syndrome of benzodiazepines is a particularly dangerous one, and due to the strong possibility of seizures, it can be fatal. The withdrawal symptoms of flunitrazepam include:

• Convulsions (seizures)
• Psychosis
• Violent behavior
• Severe depression, with possible suicidal thoughts
• Severe anxiety
• Rebound insomnia
• Nightmares
• Flu-like symptoms
• Confusion
• Restlessness
• Dysphoria - feeling physically awful - the opposite of euphoria
• Nausea and vomiting
• Poor concentration, and impaired memory
• Disturbances or increased sensitivity in touch, hearing, vision, smell and taste
• Shivering and tremor - shaking hands, etc.
• Tachycardia (fast, irregular heartbeat) and hypertension (high blood pressure)

And many more very uncomfortable and worrying symptoms. If you suspect you may be having benzodiazapine withdrawals, or are experiencing these symptoms, medical attention should be sought immediately. This withdrawal syndrome can kill, put you in a coma, cause brain damage and/or severe and dangerous psychiatric disorders, which may last a long time.

Long-term use of flunitrazepam has been postulated to cause depression.[10]

Because of its potency, it is very easy to overdose on flunitrazepam, and a dose higher than 2mgs is medically unsafe. The symptoms are simply a severe level of the normal effects - somnolence and sleepiness, unconsciousness, very slow heartbeat, very slow or labored breathing, double vision (aka diplopia), as well as confusion, agitation, slurred speech, lack of motor control, etc. If you see someone with these symptoms, and are aware they have taken flunitrazepam, an ambulance should be called for. Flunitrazepam overdose can be stopped by flumazenil, a BZD antagonist. If you have these symptoms, seek immediate medical attention - provided it's not too late. Because flunitrazepam overdose incapacitates the user, seeking help may be impossible, and this is why more than 2mgs, and/or mixing flunitrazepam with other sedating drugs, is so dangerous.

Legal Status of Flunitrazepam

Flunitrazepam is a controlled substance 21 CFR 1308.14

Australia

In Australia, flunitrazepam is classified as a schedule 8 substance, or a controlled drug, and is therefore illegal to possess without a prescription from a registered doctor.

EU

Germany

Flunitrazepam is a prescription-only medicine in Germany. It is only available in 1mg tablet form, following the Narcotic Act (the Betäubungsmittelgesetz).

UK

In the UK, flunitrazepam is available only through private prescription, and is illegal to possess without one. The sensationalism about date-rape is widespread in Britain and the drug has become notorious there. It is also occasionally used in hospitals as a pre-surgery sedative.

Republic Of Ireland

Flunitrazepam is a schedule 3 drug in Ireland, and is sold under the brand Rohypnol in 1mg and 2mg tablets. As with many countries, it is only prescribed by a doctor when other, less potent hypnotics have proved ineffective in inducing sleep, and when the patient's insomnia is causing severe distress.

USA

Due to its undue notoriety as a date-rape drug, flunitrazepam has an unusual legal status in the United States. It is classified as a schedule IV, prescription only medicine in most states, although Florida, Idaho, Minnesota, New Hampshire, New Mexico, North Dakota, Oklahoma, Pennsylvania, and Virginia have it classified as a schedule I drug, making it equally as illegal as heroin. [11]

More Flunitrazepam Sections

Flunitrazepam experiences - general discussion and experience reports. Post your experiences with flunitrazepam here.

Flunitrazepam for recreation - questioning whether or not flunitrazepam is a recreational drug or just a hypnotic.

Scheduling of fluntirazepam - interesting thread about the legal status of flunitrazepam in different countries.

References

1. ^http://www.medscape.com/viewarticle/410558_2
2. ^www.mims.com/USA/drug/info/flunitrazepam/?q...type=full
3. ^http://jaymeds.com/shop.php/flunitrazepam/i_23.html
4. ^http://chrom.tutms.tut.ac.jp/JINNO/DRUGDATA/40flunitrazepam.htm
5. ^http://www.ncbi.nlm.nih.gov/pubmed/6108669
6. ^http://informahealthcare.com/doi/abs/10.1080/004982599238056?journalCode=xen
7. ^Robertson, M., et al. Postmortem distribution and Redistribution of Nitrobenzodiazepines in Man. J.Forensic Sci. 1998:43(1):9-13
8. ^http://www.drugbank.ca/drugs/DB01544
9. ^Merck Index, 12th edition.
10. ^http://ajp.psychiatryonline.org/article.aspx?Volume=142&page=144a&journalID=13
11. ^http://www.dhra.mil/perserec/adr/drugs/rohypnol.htm

[1]Merck Index, fifteenth edition (2013)
[2]Calculated from Atomic Weights of the Elements, 2007