Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Midazolam (INN, CAS 59467-70-8), chemically 8-chloro-6-(0-fluoropheny])-1-methyl-4.4-imidazo[1,5-a][1,4]-benzodiazepine, is also known as Dormicum, Dormoniol, Hypnovel, Versed, Dormonid, and Flormidal. No stereoisomers are possible.
Similarity to known substances and effects on the CNS
Midazolam is a benzodiazepine possessing the fuil range of group-specific CNS-depressant effects of these compounds, so that it is an anxiolytic, anticonvulsant, sedative-hypnotic, muscle relaxant, etc. In animal experiments, midazolam is as efficacious as diazepam in most of its pharmacological effects, but has a more rapid onset and shorter duration of action. Clinical studies suggest that it is twice as potent as diazepam in its sedative-hypnotic effects. Midazolam itself is insoluble in water, but its salts are soluble. It has an elimination half-life of approximately 2—2.5 hours in humans. Therapeutic use of midazolam, particularly at higher doses or in the elderly, may result in cardiopulmonary disturbances.
Dependence potential
Midazolam has been demonstrated to be reinforcing in animal studies. In physical-dependence studies in animals, it substituted for phenobarbital and produced barbiturate-like withdrawal signs.
Actual abuse and or/evidence of likelihood of abuse
Abuse of midazolam, together with evidence of illicit trafficking and diversions, have been reported from a number of countries. The Committee noted reports of severe adverse cardiopulmonary effects and some deaths.
Therapeutic usefulness
Midazolam is currently available in at least 33 countries. It is marketed in the form of tablets for use in sleep disturbances and as a parenteral preparation for use as an adjunct to anaesthesia.
Recommendation
On the basis of the available data concerning its pharmacological profile, dependence potential and actual abuse, the Committee rated the abuse liability of midazolam as moderate and the therapeutic usefulness as moderate to high. Some public health and social problems are currently associated with the use of midazolam. As with all benzodiazepine agonists studied to date, it can be inferred from the preclinical studies that midazolam is capable of producing a state of dependence in human subjects similar to that observed with diazepam. In addition, the Committee noted that the availability of the substance in an injectable form enhances the likelihood of abuse. The Committee therefore considered that midazolam is likely to be abused so as to constitute a public health and social problem warranting the placing of the substance under international control. In the light of this assessment, the Committee recommended the placing of the drug in Schedule IV of the Convention on Psychotropic Substances, 1971.
Midazolam (INN, CAS 59467-70-8), chemically 8-chloro-6-(0-fluoropheny])-1-methyl-4.4-imidazo[1,5-a][1,4]-benzodiazepine, is also known as Dormicum, Dormoniol, Hypnovel, Versed, Dormonid, and Flormidal. No stereoisomers are possible.
Similarity to known substances and effects on the CNS
Midazolam is a benzodiazepine possessing the fuil range of group-specific CNS-depressant effects of these compounds, so that it is an anxiolytic, anticonvulsant, sedative-hypnotic, muscle relaxant, etc. In animal experiments, midazolam is as efficacious as diazepam in most of its pharmacological effects, but has a more rapid onset and shorter duration of action. Clinical studies suggest that it is twice as potent as diazepam in its sedative-hypnotic effects. Midazolam itself is insoluble in water, but its salts are soluble. It has an elimination half-life of approximately 2—2.5 hours in humans. Therapeutic use of midazolam, particularly at higher doses or in the elderly, may result in cardiopulmonary disturbances.
Dependence potential
Midazolam has been demonstrated to be reinforcing in animal studies. In physical-dependence studies in animals, it substituted for phenobarbital and produced barbiturate-like withdrawal signs.
Actual abuse and or/evidence of likelihood of abuse
Abuse of midazolam, together with evidence of illicit trafficking and diversions, have been reported from a number of countries. The Committee noted reports of severe adverse cardiopulmonary effects and some deaths.
Therapeutic usefulness
Midazolam is currently available in at least 33 countries. It is marketed in the form of tablets for use in sleep disturbances and as a parenteral preparation for use as an adjunct to anaesthesia.
Recommendation
On the basis of the available data concerning its pharmacological profile, dependence potential and actual abuse, the Committee rated the abuse liability of midazolam as moderate and the therapeutic usefulness as moderate to high. Some public health and social problems are currently associated with the use of midazolam. As with all benzodiazepine agonists studied to date, it can be inferred from the preclinical studies that midazolam is capable of producing a state of dependence in human subjects similar to that observed with diazepam. In addition, the Committee noted that the availability of the substance in an injectable form enhances the likelihood of abuse. The Committee therefore considered that midazolam is likely to be abused so as to constitute a public health and social problem warranting the placing of the substance under international control. In the light of this assessment, the Committee recommended the placing of the drug in Schedule IV of the Convention on Psychotropic Substances, 1971.
ECDD Recommendation
Inclusion in Schedule IV of the 1971 Convention on Psychotropic Substances
Link to full TRS
who_trs_787.pdf1.19 MB