The synthesis of clonazolam was first reported in 1971 and the drug was described as the most active compound in the series tested.[7]
Depending on dose consumed, clonazolam may pose comparatively higher risk than other designer benzodiazepines due to its ability to produce strongsedation andamnesia at doses as small as 0.5 mg.[2][8]
In the UK, clonazolam has been classified as aClass C drug by the May 2017 amendment toThe Misuse of Drugs Act 1971 along with several other designer benzodiazepine drugs.[9]
It is a Schedule I controlled substance in the United States and is notFDA approved for human consumption. Virginia state law has declared all of the following related medications are Schedule I: clonazolam,etizolam,flualprazolam,flubromazolam, andflubromazepam.[10] Minnesota declared clonazolam a Schedule I drug in August 2020.[citation needed]
On 23 December 2022, the DEA announced it had begun consideration on the matter of placing clonazolam under temporary Schedule I status.[11]
Later on 25 July 2023, the DEA published a pre-print notice that clonazolam would become temporarily scheduled as a controlled substance from 26 July 2023 to 26 July 2025.[12] On 25 July 2025, and effective the following day, the DEA extended the temporary scheduling until 26 July 2026.[13]
Clonazolam's effects are similar to other benzodiazepines, such asanxiolysis, disinhibition, lethargy, muscle relaxation, andeuphoria.[2][8] While no dose of clonazolam is considered "safe" due to its lack of research and extreme potency, doses higher than 0.5 mg can causebenzodiazepine overdose in some individuals.[2][8] The effects of a benzodiazepine overdose include sedation, confusion, amnesia, insufficient breathing, loss of consciousness, and death.[2][8] Because dependence can occur in a short period of time, or even with a large initial dose, withdrawal symptoms (including seizures and death) may occur acutely following the period of intoxication.[2][8]
^abcdefHuppertz LM, Bisel P, Westphal F, et al. (July 2015). "Characterization of the four designer benzodiazepines clonazolam, deschloroetizolam, flubromazolam, and meclonazepam, and identification of their in vitro metabolites".Forensic Toxicology.33 (2):388–395.doi:10.1007/s11419-015-0277-6.S2CID33278305.
^Meyer MR, Bergstrand MP, Helander A, Beck O (May 2016). "Identification of main human urinary metabolites of the designer nitrobenzodiazepines clonazolam, meclonazepam, and nifoxipam by nano-liquid chromatography-high-resolution mass spectrometry for drug testing purposes".Analytical and Bioanalytical Chemistry.408 (13):3571–91.doi:10.1007/s00216-016-9439-6.PMID27071765.S2CID25831532.
^Chaslot M, El Balkhi S, Robin T, Morichon J, Picard N, Saint-Marcoux F (June 2016). "Exploration des métabolites de 8 benzodiazépines de synthèse".Toxicologie Analytique et Clinique.28 (2): S32.Bibcode:2016ToxAC..28S..32C.doi:10.1016/j.toxac.2016.03.053.
^Pettersson Bergstrand M, Helander A, Hansson T, Beck O (April 2017). "Detectability of designer benzodiazepines in CEDIA, EMIT II Plus, HEIA, and KIMS II immunochemical screening assays".Drug Testing and Analysis.9 (4):640–645.doi:10.1002/dta.2003.PMID27366870.
^Høiseth G, Tuv SS, Karinen R (November 2016). "Blood concentrations of new designer benzodiazepines in forensic cases".Forensic Science International.268:35–38.doi:10.1016/j.forsciint.2016.09.006.PMID27685473.
^Hester JB, Rudzik AD, Kamdar BV (November 1971). "6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines which have central nervous system depressant activity".Journal of Medicinal Chemistry.14 (11):1078–81.doi:10.1021/jm00293a015.PMID5165540.
