Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Flunitrazepam (CAS 1622-62-4), chemically 5-(o-fluorophenyl)-1,3-dihydro-1-methy1-7-nitro-2H-1,4-benzodiazepin-2-one, is also known as Absint, Darkene, Fluninoc, Flunipam, Flunita, Flunitrazepam-ratiopharm, Hypnodorm, Hypnosedon, Inervon, Narcozep, Parnox, Primum, Rohipnol, Rohypnol, Roipnol and Valsera.
WHO review history
In 1984, flunitrazepam was included in Schedule IV of the Convention on Psychotropic Substances, 1971, together with a number of other benzodiazepines. In 1990, the 27th meeting (5) of the Committee compared 37 benzodiazepines and recommended that this drug should be kept under surveillance to determine whether it merited being placed under critical review for possible rescheduling. In 1992, the 28th meeting (6) of the Committee noted that the number of reports of illicit activities associated with flunitrazepam was higher than for any other benzodiazepine and recommended flunitrazepam for critical review.
Similarity to known substances and effects on the CNS
Flunitrazepam has typical benzodiazepine effects, with a greater sedativehypnotic potency than diazepam or chlordiazepoxide. Flunitrazepam binds with high affinity to central benzodiazepine receptors and is rapidly absorbed after oral administration. The elimination half-life of flunitrazepam following a single oral dose ranges between 9 and 25 hours in humans. Accumulation occurs with chronic administration.
Dependence potential
Drug discrimination, drug withdrawal and self-administration studies indicate that flunitrazepam has a dependence potential similar to other benzodiazepines. Rebound insomnia, considered a form of withdrawal from sedative-hypnotics, may contribute to a tendency to continue the medication. These data do not suggest any substantive difference between flunitrazepam and other benzodiazepine hypnotics. Drug preference studies in opioid users, however, have shown that flunitrazepam and diazepam stand out from other benzodiazepines by producing a strong positive reinforcing effect in these subjects. Therefore, flunitrazepam is estimated to have a moderate abuse potential which may be higher than that of other benzodiazepines. The rapid onset and longer duration of action, coupled with the stronger sedativehypnotic effects, may contribute to its higher abuse potential.
Actual abuse and or/evidence of likelihood of abuse
Available information indicates that the non-medical use or abuse of flunitrazepam is widespread among drug abusers, particularly opioid and cocaine abusers. Flunitrazepam is reported to be the most widely abused benzodiazepine by opioid abusers in many large cities in Europe, Asia and Oceania. Flunitrazepam abuse is reported even in the United States, where the drug is not marketed for therapeutic use.
Reported reasons for the abuse of flunitrazepam include potentiation of opioid effects, substitution for the opioid when it is difficult to obtain and self-medication for opioid withdrawal. Oral intake is the most common route of administration of flunitrazepam, but some abusers take the drug by intravenous injection or by "snorting". Health problems associated with the abuse of flunitrazepam include deaths directly or indirectly related to its use, drug dependence, withdrawal syndrome, paranoia,
amnesia and other psychiatric disorders.
Information on the extent of the association of 37 benzodiazepines with illicit activities during the period 1984-1989, available to the 27th meeting of the Committee in 1990, indicated a higher incidence of association with illicit activities for both diazepam and flunitrazepam than for other benzodiazepines. At that time, however, the data were not evaluated in relation to drug availability. After an adjustment for the amounts manufactured and for potency, although diazepam is no longer outstanding, flunitrazepam further stands out with respect to both seizures of the drug and the number of cases involving it.
Information on drug involvement in illicit activities after 1990, received from governments in response to the WHO questionnaire in 1994, is limited and does not allow comparison between a large number of benzodiazepines. None the less, a recent report from Interpol and an increasing use-trend in the United States, despite a lack of licit supplies in that country, together with several recent reports showing flunitrazepam as the main non-opioid drug abused by opioid abusers in major European cities, further substantiate the high abuse liability of flunitrazepam.
Therapeutic usefulness
Flunitrazepam is useful for the treatment of insomnia. It is also indicated as a pre-anaesthetic medication to assist in the induction and maintenance of anaesthesia. Flunitrazepam has a therapeutic usefulness similar to other benzodiazepine hypnotics, i.e. from moderate to great.
Recommendation
Flunitrazepam has a greater likelihood of abuse than other benzodiazepines. Although part of the reason for the abuse of flunitrazepam is self-medication for opioid withdrawal, the abuse of flunitrazepam by opioid abusers complicates its abuse profile, as it implies multiple drug dependence. Its abuse is also prevalent among youths and cocaine abusers. In addition to oral and intravenous use, abuse by "snorting" has recently been reported and as yet, no other benzodiazepine has been reported as being abused by three different routes of administration. Flunitrazepam abuse has been associated with various behavioural problems. Illicit activities involving flunitrazepam are increasing even in the United States, where it is available despite the lack of legal distribution channels.
On the basis of the available data concerning its pharmacological and toxicological profile, dependence potential and likelihood of abuse, and particularly in view of the above characteristics, the public health and social problems associated with the abuse of flunitrazepam are assessed to have become substantial. On the basis of this and the assessment of its therapeutic usefulness, it is recommended that flunitrazepam be moved from Schedule IV to Schedule III of the Convention on Psychotropic Substances, 1971.
Flunitrazepam (CAS 1622-62-4), chemically 5-(o-fluorophenyl)-1,3-dihydro-1-methy1-7-nitro-2H-1,4-benzodiazepin-2-one, is also known as Absint, Darkene, Fluninoc, Flunipam, Flunita, Flunitrazepam-ratiopharm, Hypnodorm, Hypnosedon, Inervon, Narcozep, Parnox, Primum, Rohipnol, Rohypnol, Roipnol and Valsera.
WHO review history
In 1984, flunitrazepam was included in Schedule IV of the Convention on Psychotropic Substances, 1971, together with a number of other benzodiazepines. In 1990, the 27th meeting (5) of the Committee compared 37 benzodiazepines and recommended that this drug should be kept under surveillance to determine whether it merited being placed under critical review for possible rescheduling. In 1992, the 28th meeting (6) of the Committee noted that the number of reports of illicit activities associated with flunitrazepam was higher than for any other benzodiazepine and recommended flunitrazepam for critical review.
Similarity to known substances and effects on the CNS
Flunitrazepam has typical benzodiazepine effects, with a greater sedativehypnotic potency than diazepam or chlordiazepoxide. Flunitrazepam binds with high affinity to central benzodiazepine receptors and is rapidly absorbed after oral administration. The elimination half-life of flunitrazepam following a single oral dose ranges between 9 and 25 hours in humans. Accumulation occurs with chronic administration.
Dependence potential
Drug discrimination, drug withdrawal and self-administration studies indicate that flunitrazepam has a dependence potential similar to other benzodiazepines. Rebound insomnia, considered a form of withdrawal from sedative-hypnotics, may contribute to a tendency to continue the medication. These data do not suggest any substantive difference between flunitrazepam and other benzodiazepine hypnotics. Drug preference studies in opioid users, however, have shown that flunitrazepam and diazepam stand out from other benzodiazepines by producing a strong positive reinforcing effect in these subjects. Therefore, flunitrazepam is estimated to have a moderate abuse potential which may be higher than that of other benzodiazepines. The rapid onset and longer duration of action, coupled with the stronger sedativehypnotic effects, may contribute to its higher abuse potential.
Actual abuse and or/evidence of likelihood of abuse
Available information indicates that the non-medical use or abuse of flunitrazepam is widespread among drug abusers, particularly opioid and cocaine abusers. Flunitrazepam is reported to be the most widely abused benzodiazepine by opioid abusers in many large cities in Europe, Asia and Oceania. Flunitrazepam abuse is reported even in the United States, where the drug is not marketed for therapeutic use.
Reported reasons for the abuse of flunitrazepam include potentiation of opioid effects, substitution for the opioid when it is difficult to obtain and self-medication for opioid withdrawal. Oral intake is the most common route of administration of flunitrazepam, but some abusers take the drug by intravenous injection or by "snorting". Health problems associated with the abuse of flunitrazepam include deaths directly or indirectly related to its use, drug dependence, withdrawal syndrome, paranoia,
amnesia and other psychiatric disorders.
Information on the extent of the association of 37 benzodiazepines with illicit activities during the period 1984-1989, available to the 27th meeting of the Committee in 1990, indicated a higher incidence of association with illicit activities for both diazepam and flunitrazepam than for other benzodiazepines. At that time, however, the data were not evaluated in relation to drug availability. After an adjustment for the amounts manufactured and for potency, although diazepam is no longer outstanding, flunitrazepam further stands out with respect to both seizures of the drug and the number of cases involving it.
Information on drug involvement in illicit activities after 1990, received from governments in response to the WHO questionnaire in 1994, is limited and does not allow comparison between a large number of benzodiazepines. None the less, a recent report from Interpol and an increasing use-trend in the United States, despite a lack of licit supplies in that country, together with several recent reports showing flunitrazepam as the main non-opioid drug abused by opioid abusers in major European cities, further substantiate the high abuse liability of flunitrazepam.
Therapeutic usefulness
Flunitrazepam is useful for the treatment of insomnia. It is also indicated as a pre-anaesthetic medication to assist in the induction and maintenance of anaesthesia. Flunitrazepam has a therapeutic usefulness similar to other benzodiazepine hypnotics, i.e. from moderate to great.
Recommendation
Flunitrazepam has a greater likelihood of abuse than other benzodiazepines. Although part of the reason for the abuse of flunitrazepam is self-medication for opioid withdrawal, the abuse of flunitrazepam by opioid abusers complicates its abuse profile, as it implies multiple drug dependence. Its abuse is also prevalent among youths and cocaine abusers. In addition to oral and intravenous use, abuse by "snorting" has recently been reported and as yet, no other benzodiazepine has been reported as being abused by three different routes of administration. Flunitrazepam abuse has been associated with various behavioural problems. Illicit activities involving flunitrazepam are increasing even in the United States, where it is available despite the lack of legal distribution channels.
On the basis of the available data concerning its pharmacological and toxicological profile, dependence potential and likelihood of abuse, and particularly in view of the above characteristics, the public health and social problems associated with the abuse of flunitrazepam are assessed to have become substantial. On the basis of this and the assessment of its therapeutic usefulness, it is recommended that flunitrazepam be moved from Schedule IV to Schedule III of the Convention on Psychotropic Substances, 1971.
ECDD Recommendation
Rescheduled from Schedule IV to Schedule III of the 1971 Convention on Psychotropic Substances
Link to full TRS
who_trs_856.pdf1.07 MB