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Federal Register / Vol. 86, No. 31 / Thursday, February 18, 2021 / Notices onset of withdrawal symptoms after cessation of use have been reported on online forums.

Therapeutic Usefulness
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Diphenidine is not known to have any therapeutic use.
Recommendation
Actual Abuse and/or Evidence of Likelihood of Abuse
The available evidence indicates that diphenidine Chemical name: 1-1,2diphenylethylpiperidine has a mechanism of action and effects that are similar to those of phencyclidine PCP, which is controlled under Schedule II of the 1971 Convention on Psychotropic Substances. Its mode of action suggests a likelihood of abuse. There is evidence of significant harm due to diphenidine, including psychosis and cardiovascular effects, which represents a substantial risk to public health. Diphenidine has no therapeutic use.
The Committee recommended that diphenidine Chemical name: 1-1,2diphenylethylpiperidine be added to Schedule II of the Convention on Psychotropic Substances of 1971.
Substances recommended to be scheduled in Schedule IV of the Convention on Psychotropic Substances 1971:

No human or animal studies have examined abuse liability. Online forums describe its recreational use and consistently report its strong anxiolytic effects.
A number of published reports describe the management of cases of intoxication involving clonazolam in emergency departments or intensive care. Clonazolam use has been analytically confirmed in cases of impaired driving, in combination with other substances. Clonazolam has the potential to 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.
There are reports of its identification in multiple countries representing all regions, indicating that its use may be increasing.
Clonazolam is increasingly sold as falsified pharmaceutical benzodiazepines.

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

Clonazolam Chemical name: 6-2chlorophenyl-1-methyl-8-nitro-4Hbenzof1,2,4triazolo4,3-a1,4diazepine is 1-4 triazolobenzodiazepine similar to clonazepam, triazolam and alprazolam. It is sold in powder, blotter, liquid and tablet form.
WHO Review History Clonazolam has never been formally reviewed by WHO and is not currently under international control. Information was brought to WHOs attention that this substance is clandestinely manufactured, poses a risk to public health, and has no recognized therapeutic use.
Similarity to Known Substances and Effects on Central Nervous System Clonazolam enhances the effects of the inhibitory neurotransmitter gammaaminobutyric acid GABA through binding at the benzodiazepine site of the GABA-A
receptor. This mechanism of action, as well as its effects sedation, muscle relaxation, slurred speech and loss of motor control, amnesia are similar to those of the benzodiazepines such as diazepam, triazolam and alprazolam which are controlled under Schedule IV of the 1971
Convention on Psychotropic Substances.
In cases of clonazolam poisoning, the effects have been reversed with the benzodiazepine antagonist flumazenil, confirming that its action is mediated via the benzodiazepine receptor in the GABA-A
receptor complex.
Dependence Potential No controlled animal or human studies have examined the dependence potential of clonazolam, though based on its pharmacological effects, and similarity to other benzodiazepines, it would be expected to have potential to produce dependence.
The development of tolerance to the effects of clonazolam following repeated use and the
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Recommendation Clonazolam Chemical name: 6-2chlorophenyl-1-methyl-8-nitro-4Hbenzof1,2,4triazolo4,3-a1,4diazepine is a 1-4 triazolobenzodiazepine that has 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 nonfatal intoxications. There is sufficient evidence of its abuse so as to constitute a public health problem, and it has no known therapeutic use.
The Committee recommended that clonazolam Chemical name: 6-2chlorophenyl-1-methyl-8-nitro-4Hbenzof1,2,4triazolo4,3-a1,4diazepine be added to Schedule IV of the 1971
Convention on Psychotropic Substances.
Diclazepam Substance Identification Diclazepam Chemical name: 7-chloro-5-2chlorophenyl-1-methyl-1,3-dihydro-2Hbenzoe1,4diazepin2-one is a 2-chloro derivative of the benzodiazepine diazepam. It appears as a white powder, and is commonly sold as tablets, pellets and liquid.
WHO Review History Diclazepam has never been formally reviewed by WHO and is not currently under international control. Information was brought to WHOs attention that this substance is clandestinely manufactured, poses a risk to public health, and has no recognized therapeutic use.

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Similarity to Known Substances and Effects on Central Nervous System Diclazepam is an agonist at the benzodiazepine site of the GABA-A receptor, acting to increase the effect of the inhibitory neurotransmitter gamma amino butyric acid GABA. Diclazepam has similar effects to the benzodiazepine diazepam, which is currently controlled under the Convention on Psychotropic Substances of 1971. It is metabolized to the benzodiazepines delorazepam, lorazepam and lormetazepam.
These metabolites are active and are also pharmaceuticals that are included in Schedule IV of the Convention on Psychotropic Substances of 1971.
Diclazepam has been demonstrated to cause sedation and muscle relaxation in animals. Central nervous systems depressant effects are also described in humans.
Dependence Potential No controlled animal or human studies have examined the dependence potential of diclazepam.
Online user reports describe crosstolerance with other benzodiazepines and use to self-manage benzodiazepine withdrawal. This evidence, along with its mechanism of action, suggests that diclazepam has the capacity to produce dependence similar to other benzodiazepines.
Actual Abuse and/or Evidence of Likelihood of Abuse No controlled animal or human studies have examined the abuse liability of diclazepam. However, based on its mechanism of action and effects, it would be expected to have abuse liability similar to other benzodiazepines.
Diclazepam has the potential to increase unintentional opioid overdoses. Its long halflife may increase the risk of accumulation and interactions when combined with other drugs. Fatal intoxications with diclazepam have been reported.
Seizures of diclazepam have been reported from multiple countries across different regions. Diclazepam is increasingly sold as falsified benzodiazepines, commonly as diazepam.
Diclazepam has been implicated in cases of impaired driving, including cases where diclazepam was identified as the main contributor to impairment. It also has been involved in cases of drug-facilitated sexual assault.
Therapeutic Usefulness Diclazepam is not known to have any therapeutic use, is not listed on the WHO
Model List of Essential Medicines and has never been marketed as a medicinal product.
Recommendation Diclazepam Chemical name: 7-chloro-5-2chlorophenyl-1-methyl-1,3-dihydro-2Hbenzoe1,4diazepin2-one is a 2-chloro analogue of the benzodiazepine diazepam that has actions and effects very similar to those of benzodiazepines listed under Schedule IV of the Convention on Psychotropic Substances of 1971. It can produce a state of dependence and central nervous system depression, like other
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