Clonazolam

IUPAC Name

1-[1-(3-methoxyphenyl)cyclohexyl]piperidine

Year(s) and type of review / ECDD meetings
Drug Class
ECDD Recommendation
Inclusion in Schedule IV of the 1971 Convention on Psychotropic Substances
Recommendation (from TRS)
Substance identification
Clonazolam (chemical name: 6-(2-chlorophenyl)-1-methyl-8-nitro-4H- benzo[f][1,2,4]triazolo[4,3- a][1,4]diazepine) is a 1-4 triazolobenzodiazepine similar to clonazepam, triazolam and alprazolam. It is sold in powder, blotter, liquid and tablet forms.

WHO review history
Clonazolam has not been formally reviewed by WHO and is not currently under international control. Information was brought to WHO’s attention that this substance is manufactured clandestinely, poses a risk to public health and has no recognized therapeutic use.

Similarity to known substances and effects on the central nervous system
Clonazolam enhances the effects of the inhibitory neurotransmitter GABA by binding at the benzodiazepine site of the GABAA receptor. This mechanism of action and its effects (sedation, muscle relaxation, slurred speech, loss of motor control, amnesia) are similar to those of benzodiazepines such as diazepam, triazolam and alprazolam, which are controlled under Schedule IV of the 1971 Convention on Psychotropic Substances. The effects of clonazolam poisoning have been reversed with the benzodiazepine antagonist flumazenil, confirming that its action is mediated via the benzodiazepine receptor in the GABAA receptor complex.

Dependence potential
No controlled studies have been reported in animals or humans on the dependence potential of clonazolam, although its pharmacological effects and its similarity to other benzodiazepines indicate that it would be expected to produce dependence.

Development of tolerance to the effects of clonazolam after repeated use and the onset of withdrawal symptoms after cessation of use have been reported on online forums.

Actual abuse and/or evidence of likelihood of abuse
No studies in humans or animals have examined the abuse liability of clonazolam. Online forums describe its recreational use and consistently report strong anxiolytic effects. A number of published reports describe the management of cases of intoxication involving clonazolam in emergency departments or intensive care. Use of clonazolam has been confirmed analytically in cases of impaired driving, in combination with other substances. Clonazolam can increase the effects of other drugs, including opioids, and on its own can cause severe central nervous system depression, including somnolence, confusion, sedation and unconsciousness.

Its identification has been reported in many countries in all regions, indicating that its use may be increasing. Clonazolam is increasingly sold as falsified pharmaceutical benzodiazepines.

Therapeutic usefulness
Clonazolam is not known to have any therapeutic use, is not on the WHO Model List of Essential Medicines and has never been marketed as a medicinal product.

Recommendation
Clonazolam (chemical name: 6-(2-chlorophenyl)-1-methyl-8-nitro-4H- benzo[f][1,2,4]triazolo[4,3- a][1,4]diazepine) is a 1-4 triazolobenzodiazepine with actions and effects very similar to those of benzodiazepines listed under Schedule IV in the Convention on Psychotropic Substances of 1971. Like other benzodiazepines, clonazolam can produce a state of dependence and central nervous system depression. There have been a number of reports of abuse, impaired driving and non-fatal intoxications. There is sufficient evidence of its abuse to constitute a public health problem, and it has no known therapeutic use.

Recommendation: The Committee recommend that clonazolam (chemical name: 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-benzo[f][1,2,4]triazolo[4,3- a][1,4]diazepine) be added to Schedule IV of the 1971 Convention on Psychotropic Substances.