This is an unofficial archive of PsychonautWiki as of 2025-08-11T15:14:44Z. Content on this page may be outdated, incomplete, or inaccurate. Please refer to the original page for the most up-to-date information.
m Made half-life info more concise, and added a reference. This is my first wiki editing ever, so the ref might not be right; it's the same used at Wikipedia. :P
'''Clonazepam'''<ref>US Patent 3123529</ref> (trade name '''Klonopin''' or Rivotril) is a long-acting [[psychoactive]] substance of the [[chemical class::benzodiazepine]] class which produces [[anxiolytic]], [[anticonvulsant]], [[muscle relaxant]], [[amnesic]], [[sedative]], [[psychoactive class::depressant]] and [[hypnotic]] effects.<ref>Ethyl beta-carboline carboxylate lowers seizure threshold and antagonizes flurazepam-induced sedation in rats (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/6259533</ref> It is commonly used and FDA approved for the medical treatment of panic disorder, generalized [[anxiety]] disorder (GAD), and social anxiety disorder (SAD).
'''Clonazepam'''<ref>{{Citation | title=Patent US3123529 | url=https://www.freepatentsonline.com/3123529.pdf}}</ref> (trade name '''Klonopin''' or '''Rivotril''') is a long-acting [[psychoactive]] substance of the [[chemical class::benzodiazepine]] class which produces [[anxiolytic|mainly anxiolytic]], but also [[anticonvulsant]], [[muscle relaxant]], [[amnesic]], [[sedative]], [[psychoactive class::depressant]] and [[hypnotic]] effects.<ref>{{cite journal | vauthors=((Cowen, P. J.)), ((Green, A. R.)), ((Nutt, D. J.)) | journal=Nature | title=Ethyl beta-carboline carboxylate lowers seizure threshold and antagonizes flurazepam-induced sedation in rats | volume=290 | issue=5801 | pages=54–55 | date=5 March 1981 | issn=0028-0836 | doi=10.1038/290054a0}}</ref> It is commonly used and FDA approved for the medical treatment of panic disorder, generalized [[anxiety]] disorder (GAD), and social anxiety disorder (SAD). In Europe, it is generally approved for treatment-resistent epilepsy.
Clonazepam has an elimination half-life of 19 – 60 hours<ref>Riss, J.; Cloyd, J.; Gates, J.; Collins, S. (August 2008). "Benzodiazepines in epilepsy: pharmacology and pharmacokinetics". Acta Neurol Scand. 118 (2): 69–86. | https://doi.org/10.1111%2Fj.1600-0404.2008.01004.x</ref>, and is generally considered to be a long-acting benzodiazepine. Clonazepam has an intermediate onset of action, with a peak blood level occurring one to four hours after oral administration.
Clonazepam has an elimination half-life of 30 – 40 hours<ref>Basit H, Kahwaji CI. Clonazepam. [Updated 2022 Sep 1]. In: StatPearls [https://www.ncbi.nlm.nih.gov/books/NBK556010/]</ref>, and is considered to be a long-acting benzodiazepine. Clonazepam has rapid onset of action, with a peak blood level occurring one to four hours after oral administration.
It's worth noting that [[Benzodiazepine#Discontinuation|the sudden discontinuation of benzodiazepines]] can be potentially life-threatening for individuals using regularly for extended periods of time.<ref>A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812</ref> It is highly recommended to [[taper]] one's dose by gradually lowering the amount taken each day for a prolonged period of time instead of stopping abruptly.<ref>Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain - Appendix B-6: Benzodiazepine Tapering | http://nationalpaincentre.mcmaster.ca/opioid/cgop_b_app_b06.html</ref>
It's worth noting that [[Benzodiazepine#Discontinuation|the sudden discontinuation of benzodiazepines]] can be potentially life-threatening for individuals using regularly for extended periods of time.<ref name="Lann2009">{{cite journal | vauthors=((Lann, M. A.)), ((Molina, D. K.)) | journal=The American Journal of Forensic Medicine and Pathology | title=A fatal case of benzodiazepine withdrawal | volume=30 | issue=2 | pages=177–179 | date= June 2009 | issn=1533-404X | doi=10.1097/PAF.0b013e3181875aa0}}</ref> It is highly recommended to [[taper]] one's dose by gradually lowering the amount taken each day for a prolonged period of time instead of stopping abruptly.<ref>{{cite journal | vauthors=((Kahan, M.)), ((Mailis-Gagnon, A.)), ((Tunks, E.)) | journal=Pain Research & Management | title=Canadian guideline for safe and effective use of opioids for chronic non-cancer pain: implications for pain physicians | volume=16 | issue=3 | pages=157–158 | date= June 2011 | issn=1203-6765 | doi=10.1155/2011/434298}}</ref> Not doing so can lead to serious health problems and even death.
==Chemistry==
==Chemistry==
Clonazepam is a drug of the [[benzodiazepine]] class. Benzodiazepine drugs contain a benzene ring fused to a diazepine ring, which is a seven membered ring with the two nitrogen constituents located at R<sub>1</sub> and R<sub>4</sub>. The benzyl ring of clonazepam is substituted at R<sub>8</sub> with a nitro group, NO<sub>2</sub>-. Further, the diazepine ring is bonded at R<sub>5</sub> to a 2-chlorinated phenyl ring. Clonazepam also contains an oxygen group double bonded to R<sub>2</sub> of its diazepine ring to form a ketone. This oxygen substitution at R<sub>2</sub> is shared with other benzodiazepine drugs with the suffix -azepam.
Clonazepam is a drug of the [[benzodiazepine]] class. Benzodiazepine drugs contain a benzene ring fused to a diazepine ring, which is a seven membered ring with the two nitrogen constituents located at R<sub>1</sub> and R<sub>4</sub>. The benzyl ring of clonazepam is substituted at R<sub>8</sub> with a nitro group, NO<sub>2</sub>-. Further, the diazepine ring is bonded at R<sub>5</sub> to a 2-chlorinated phenyl ring. Clonazepam also contains an oxygen group double bonded to R<sub>2</sub> of its diazepine ring to form a ketone. This oxygen substitution at R<sub>2</sub> is shared with other benzodiazepine drugs with the suffix -azepam.
==Pharmacology==
==Pharmacology==
Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter [[GABA|gamma aminobutyric acid (GABA)]] by acting on its [[receptor]]s.<ref>Benzodiazepine interactions with GABA receptors (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6147796</ref> As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the [[sedating]] (or [[anxiety suppression|calming effects]]) of clonazepam on the nervous system.
Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter [[GABA|gamma aminobutyric acid (GABA)]] by acting on its [[receptor]]s.<ref>{{cite journal | vauthors=((Haefely, W.)) | journal=Neuroscience Letters | title=Benzodiazepine interactions with GABA receptors | volume=47 | issue=3 | pages=201–206 | date=29 June 1984 | issn=0304-3940 | doi=10.1016/0304-3940(84)90514-7}}</ref> As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the [[sedating]] (or [[anxiety suppression|calming effects]]) of clonazepam on the nervous system.
The [[anticonvulsant]] properties of benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.<ref>Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/2450203</ref>
The [[anticonvulsant]] properties of benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.<ref>{{cite journal | vauthors=((McLean, M. J.)), ((Macdonald, R. L.)) | journal=The Journal of Pharmacology and Experimental Therapeutics | title=Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture | volume=244 | issue=2 | pages=789–795 | date= February 1988 | issn=0022-3565}}</ref>
==Subjective effects==
==Subjective effects==
{{Preamble/SubjectiveEffects}}
{{Preamble/SubjectiveEffects}}
{{effects/base
{{effects/base
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*'''[[Effect::Respiratory depression]]'''
*'''[[Effect::Respiratory depression]]'''
*'''[[Effect::Seizure suppression]]'''
*'''[[Effect::Seizure suppression]]'''
*'''[[Effect::Physical euphoria]]''' - Clonazepam is similar to [[alprazolam]], where despite suppressing emotion, people report moderate-strong feelings of relaxation, pleasure and comfort in the body. This seems to present itself more often in those with pre-existing [[anxiety]] However, this isn't consistent with everyone, with some users reporting no euphoric qualities at all.
*'''[[Effect::Physical euphoria]]''' - Clonazepam is similar to [[alprazolam]], where despite suppressing emotion, people report moderate-strong feelings of relaxation, pleasure and comfort in the body. This seems to present itself more often in those with pre-existing [[anxiety]]. However, this isn't consistent with everyone, with some users reporting no euphoric qualities at all.
}}
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}}
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{{effects/paradoxical|
{{effects/paradoxical|
Paradoxical reactions to [[benzodiazepines]] such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%).<ref>http://www.ncbi.nlm.nih.gov/pubmed/18922233 | Saïas T, Gallarda T | Paradoxical aggressive reactions to benzodiazepine use: a review</ref><ref>Paton C | Benzodiazepines and disinhibition: a review | Psychiatr Bull R Coll Psychiatr | http://pb.rcpsych.org/cgi/reprint/26/12/460.pdf</ref>
Paradoxical reactions to [[benzodiazepines]] such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%).<ref>{{cite journal | vauthors=((Saïas, T.)), ((Gallarda, T.)) | journal=L’Encephale | title=[Paradoxical aggressive reactions to benzodiazepine use: a review] | volume=34 | issue=4 | pages=330–336 | date= September 2008 | issn=0013-7006 | doi=10.1016/j.encep.2007.05.005}}</ref><ref>{{cite journal | vauthors=((Paton, C.)) | journal=Psychiatric Bulletin | title=Benzodiazepines and disinhibition: a review | volume=26 | issue=12 | pages=460–462 | date= December 2002 | url=https://www.cambridge.org/core/journals/psychiatric-bulletin/article/benzodiazepines-and-disinhibition-a-review/421AF197362B55EDF004700452BF3BC6 | issn=0955-6036 | doi=10.1192/pb.26.12.460}}</ref>
These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.<ref>Bond AJ | Drug-induced behavioural disinhibition: incidence, mechanisms and therapeutic implications | CNS Drugs</ref><ref>Drummer OH | Benzodiazepines—effects on human performance and behavior | Forensic Sci Rev</ref>
These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.<ref>{{cite journal | vauthors=((Bond, A. J.)) | journal=CNS Drugs | title=Drug- Induced Behavioural Disinhibition | volume=9 | issue=1 | pages=41–57 | date=1 January 1998 | url=https://doi.org/10.2165/00023210-199809010-00005 | issn=1179-1934 | doi=10.2165/00023210-199809010-00005}}</ref>
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*'''[[Effect::Anxiety|Rebound anxiety]]''' - Rebound anxiety is a commonly observed effect with [[anxiety suppression|anxiety relieving]] substances like [[benzodiazepines]]. It typically corresponds to the total duration spent under the substance's influence along with the total amount consumed in a given period, an effect which can easily lend itself to cycles of dependence and addiction.
*'''[[Effect::Anxiety|Rebound anxiety]]''' - Rebound anxiety is a commonly observed effect with [[anxiety suppression|anxiety relieving]] substances like [[benzodiazepines]]. It typically corresponds to the total duration spent under the substance's influence along with the total amount consumed in a given period, an effect which can easily lend itself to cycles of dependence and addiction.
*'''[[Effect::Dream potentiation]]'''<ref>Goyal, Sarita. "Drugs and Dreams." Indian Journal of Clinical Practice (n.d.): n. pag. Web. | http://medind.nic.in/iaa/t13/i3/iaat13i3p624.pdf</ref> or '''[[Effect::Dream suppression]]'''
*'''[[Effect::Dream potentiation]]'''<ref>{{cite journal | vauthors=((Goyal, S.)) | journal=Canadian Medical Association Journal | title=Drugs and dreams | volume=102 | issue=5 | pages=524 | date=14 March 1970 | issn=0008-4409}}</ref> or '''[[Effect::Dream suppression]]'''
*'''[[Effect::Sleepiness|Residual sleepiness]]''' - While benzodiazepines can be used as an effective [[hypnotic|sleep-inducing]] aid, their effects may persist into the morning afterward, which may lead users to feeling "groggy" or "dull" for up to a few hours.
*'''[[Effect::Sleepiness|Residual sleepiness]]''' - While benzodiazepines can be used as an effective [[hypnotic|sleep-inducing]] aid, their effects may persist into the morning afterward, which may lead users to feeling "groggy" or "dull" for up to a few hours.
*'''[[Effect::Thought deceleration]]'''
*'''[[Effect::Thought deceleration]]'''
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==Toxicity and harm potential==
==Toxicity and harm potential==
[[File:harmchart.png|thumb|right|300px|Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.<ref>Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644</ref>]]
[[File:harmchart.png|thumb|right|300px|Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.<ref>{{cite journal | vauthors=((Nutt, D.)), ((King, L. A.)), ((Saulsbury, W.)), ((Blakemore, C.)) | journal=The Lancet | title=Development of a rational scale to assess the harm of drugs of potential misuse | volume=369 | issue=9566 | pages=1047–1053 | date=24 March 2007 | url=https://www.sciencedirect.com/science/article/pii/S0140673607604644 | issn=0140-6736 | doi=10.1016/S0140-6736(07)60464-4}}</ref>]]
Clonazepam has a [[Toxicity::low toxicity]] relative to dose.<ref>Mandrioli R, Mercolini L, Raggi MA. Benzodiazepine metabolism: an analytical perspective. Curr Drug Metab. 2008 Oct;9(8):827-44. doi: 10.2174/138920008786049258. PMID: 18855614. | http://www.ncbi.nlm.nih.gov/pubmed/18855614</ref> However, it is [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[opioids]]]].
Clonazepam has a [[Toxicity::low toxicity]] relative to dose.<ref>{{cite journal | vauthors=((Mandrioli, R.)), ((Mercolini, L.)), ((Raggi, M. A.)) | journal=Current Drug Metabolism | title=Benzodiazepine Metabolism: An Analytical Perspective | volume=9 | issue=8 | pages=827–844 | url=https://www.eurekaselect.com/article/12780}}</ref> However, it is [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[opioids]]]].
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
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Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction. For more information on tapering from benzodiazepines in a controlled manner, please see [http://www.benzo.org.uk/manual/bzcha02.htm this guide].
Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction. For more information on tapering from benzodiazepines in a controlled manner, please see [http://www.benzo.org.uk/manual/bzcha02.htm this guide].
[[Benzodiazepine#Discontinuation|Benzodiazepine discontinuation]] is notoriously difficult; it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of [[hypertension]], [[seizures]], and death.<ref>Lann MA, Molina DK. A fatal case of benzodiazepine withdrawal. Am J Forensic Med Pathol. 2009 Jun;30(2):177-9. doi: 10.1097/PAF.0b013e3181875aa0. PMID: 19465812. | http://www.ncbi.nlm.nih.gov/pubmed/19465812</ref> Drugs which lower the seizure threshold such as [[tramadol]] should be avoided during withdrawal.
[[Benzodiazepine#Discontinuation|Benzodiazepine discontinuation]] is notoriously difficult; it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of [[hypertension]], [[seizures]], and death.<ref name="Lann2009" /> Drugs which lower the seizure threshold such as [[tramadol]] should be avoided during withdrawal.
Clonazopam presents cross-tolerance with [[Cross-tolerance::all [[benzodiazepines]]]], meaning that after its consumption all benzodiazepines will have a reduced effect.
Clonazepam presents cross-tolerance with [[Cross-tolerance::all [[benzodiazepines]]]], meaning that after its consumption all benzodiazepines will have a reduced effect.
===Overdose===
===Overdose===
Benzodiazepine overdose may occur when a [[benzodiazepine]] is taken in extremely heavy quantities or concurrently with other depressants. This is particularly dangerous with other GABAergic depressants such as [[barbiturate |barbiturates]] and [[alcohol]] since they work in a similar fashion, but bind to distinct allosteric sites on the GABA<sub>A</sub> receptor, thus their effects potentiate one another. Benzodiazepines increase the frequency in which the chlorine ion pore opens on the GABA<sub>A</sub> receptor while barbiturates increase the duration in which they are open, meaning when both are consumed, the ion pore will open more frequently and stay open longer<ref>Twyman RE, Rogers CJ, Macdonald RL. Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital. Ann Neurol. 1989 Mar;25(3):213-20. doi: 10.1002/ana.410250302. PMID: 2471436. | https://www.ncbi.nlm.nih.gov/pubmed/2471436</ref>. Benzodiazepine overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly and properly.
Benzodiazepine overdose may occur when a [[benzodiazepine]] is taken in extremely heavy quantities or concurrently with other depressants. This is particularly dangerous with other GABAergic depressants such as [[barbiturate |barbiturates]] and [[alcohol]] since they work in a similar fashion, but bind to distinct allosteric sites on the GABA<sub>A</sub> receptor, thus their effects potentiate one another. Benzodiazepines increase the frequency in which the chlorine ion pore opens on the GABA<sub>A</sub> receptor while barbiturates increase the duration in which they are open, meaning when both are consumed, the ion pore will open more frequently and stay open longer<ref>{{cite journal | vauthors=((Twyman, R. E.)), ((Rogers, C. J.)), ((Macdonald, R. L.)) | journal=Annals of Neurology | title=Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital | volume=25 | issue=3 | pages=213–220 | date= March 1989 | issn=0364-5134 | doi=10.1002/ana.410250302}}</ref>. Benzodiazepine overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly and properly.
Symptoms of a benzodiazepine overdose may include severe [[thought deceleration]], [[language suppression |slurred speech]], [[confusion]], [[delusions]], [[respiratory depression]], coma or death. Benzodiazepine overdoses may be treated effectively in a hospital environment, with generally favorable outcomes. Benzodiazepine overdoses are sometimes treated with [[flumazenil]], a GABA<sub>A</sub> antagonist<ref>Hoffman EJ, Warren EW. Flumazenil: a benzodiazepine antagonist. Clin Pharm. 1993 Sep;12(9):641-56; quiz 699-701. Erratum in: Clin Pharm 1993 Nov;12(11):803. PMID: 8306565. | https://www.ncbi.nlm.nih.gov/pubmed/8306565</ref>, however care is primarily supportive in nature.
Symptoms of a benzodiazepine overdose may include severe [[thought deceleration]], [[language suppression |slurred speech]], [[confusion]], [[delusions]], [[respiratory depression]], coma or death. Benzodiazepine overdoses may be treated effectively in a hospital environment, with generally favorable outcomes. Benzodiazepine overdoses are sometimes treated with [[flumazenil]], a GABA<sub>A</sub> antagonist<ref>{{cite journal | vauthors=((Hoffman, E. J.)), ((Warren, E. W.)) | journal=Clinical Pharmacy | title=Flumazenil: a benzodiazepine antagonist | volume=12 | issue=9 | pages=641–656; quiz 699–701 | date= September 1993 | issn=0278-2677}}</ref>, however care is primarily supportive in nature.
===Dangerous interactions===
===Dangerous interactions===
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*'''Brazil''': Clonazepam is a "black stripe" drug, which are available by prescription only.<ref>[http://www.anvisa.gov.br/datavisa/fila_bula/frmVisualizarBula.asp?pNuTransacao=8688542015&pIdAnexo=2876451 Anvisa]</ref>
*'''Brazil''': Clonazepam is a "black stripe" drug, which are available by prescription only.<ref>[http://www.anvisa.gov.br/datavisa/fila_bula/frmVisualizarBula.asp?pNuTransacao=8688542015&pIdAnexo=2876451 Anvisa]</ref>
*'''Canada''': Clonazepam is a Schedule IV drug.{{citation needed}}
*'''Canada''': Clonazepam is a Schedule IV drug.{{citation needed}}
*'''Czech Republic''': Clonazepam is a Schedule IV <ref>https://eur-lex.europa.eu/resource.html?uri=cellar:6b5e9beb-1d9b-11ea-95ab-01aa75ed71a1.0001.02/DOC_1&format=PDF</ref> (List 7) substance. Sold exclusively by prescription "without a blue stripe" (§ 1, g), 2. of ''Nařízení vlády č. 463/2013 Sb.''). <ref>https://www.zakonyprolidi.cz/cs/2013-463</ref>
*'''Germany''': Clonazepam is controlled under Anlage III BtMG (''Narcotics Act, Schedule III'') as of August 1, 1986.<ref>{{cite web|url=http://www.bgbl.de/xaver/bgbl/start.xav?startbk=Bundesanzeiger_BGBl&jumpTo=bgbl186s1099.pdf|title=Zweite Verordnung zur Änderung betäubungsmittelrechtlicher Vorschriften|publisher=Bundesanzeiger Verlag|access-date=December 26, 2019|language=de}}</ref> It can only be prescribed on a narcotic prescription form, except preparations which contain up to 2 mg clonazepam in each dosage form and solutions that contain up to 0.25% and under 250 mg clonazepam in total per packaging unit.<ref>{{cite web|url=https://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html|title=Anlage III BtMG|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 26, 2019|language=de}}</ref>
*'''Germany''': Clonazepam is controlled under Anlage III BtMG (''Narcotics Act, Schedule III'') as of August 1, 1986.<ref>{{cite web|url=http://www.bgbl.de/xaver/bgbl/start.xav?startbk=Bundesanzeiger_BGBl&jumpTo=bgbl186s1099.pdf|title=Zweite Verordnung zur Änderung betäubungsmittelrechtlicher Vorschriften|publisher=Bundesanzeiger Verlag|access-date=December 26, 2019|language=de}}</ref> It can only be prescribed on a narcotic prescription form, except preparations which contain up to 2 mg clonazepam in each dosage form and solutions that contain up to 0.25% and under 250 mg clonazepam in total per packaging unit.<ref>{{cite web|url=https://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html|title=Anlage III BtMG|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 26, 2019|language=de}}</ref>
*'''India''': Clonazepam is Schedule H in India.{{citation needed}}
*'''India''': Clonazepam is Schedule H in India.{{citation needed}}
*'''Israel''': Clonazepam is available by prescription only.{{citation needed}}
*'''Israel''': Clonazepam is available by prescription only.{{citation needed}}
*'''New Zeland''': Clonazepam is a Schedule 3 controlled drug.<ref>{{Citation | title=Misuse of Drugs Act 1975 No 116 (as at 01 July 2022), Public Act Schedule 3 Class C controlled drugs – New Zealand Legislation | url=https://www.legislation.govt.nz/act/public/1975/0116/latest/DLM436723.html}}</ref>
*'''Norway''': Clonazepam is available by prescription only.<ref>https://www.felleskatalogen.no/medisin/rivotril-roche-563568</ref>
*'''Norway''': Clonazepam is available by prescription only.<ref>https://www.felleskatalogen.no/medisin/rivotril-roche-563568</ref>
*'''Russia''': Clonazepam is a Schedule III controlled substance as of April 2013.<ref>Постановление Правительства РФ от 04.02.2013 N 78 | https://www.consultant.ru/cons/cgi/online.cgi?req=doc&base=LAW&n=141744&dst=100005&date=02.12.2019</ref>
*'''Russia''': Clonazepam is a Schedule III controlled substance as of April 2013.<ref>{{Citation | title=Постановление Правительства РФ от 04.02.2013 N 78 “О внесении изменений в некоторые акты Правительства Российской Федерации” - КонсультантПлюс | url=https://www.consultant.ru/cons/cgi/online.cgi?req=doc&base=LAW&n=141744&dst=100005&date=02.12.2019}}</ref>
*'''Switzerland''': Clonazepam is a controlled substance specifically named under Verzeichnis B. Medicinal use is permitted.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''Switzerland''': Clonazepam is a controlled substance specifically named under Verzeichnis B. Medicinal use is permitted.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''Turkey''': Clonazepam is a 'green prescription' only substance<ref>YEŞİL REÇETEYE TABİ İLAÇLAR | https://www.titck.gov.tr/storage/Archive/2019/contentFile/01.04.2019%20SKRS%20Ye%C5%9Fil%20Re%C3%A7eteli%20%C4%B0la%C3%A7lar%20Aktif%20SON%20-%20G%C3%9CNCEL_58b1ff4a-2e1c-4867-bad7-eec855d6162a.pdf</ref> and illegal when sold or possessed without a prescription.{{citation needed}}
*'''Turkey''': Clonazepam is a 'green prescription' only substance<ref>YEŞİL REÇETEYE TABİ İLAÇLAR | https://www.titck.gov.tr/storage/Archive/2019/contentFile/01.04.2019%20SKRS%20Ye%C5%9Fil%20Re%C3%A7eteli%20%C4%B0la%C3%A7lar%20Aktif%20SON%20-%20G%C3%9CNCEL_58b1ff4a-2e1c-4867-bad7-eec855d6162a.pdf</ref> and illegal when sold or possessed without a prescription.{{citation needed}}
*'''United Kingdom''': Clonazepam is a Class C drug.{{citation needed}}
*'''United Kingdom''': Clonazepam is a Class C drug. <ref>{{Citation | title=List of most commonly encountered drugs currently controlled under the misuse of drugs legislation | url=https://www.gov.uk/government/publications/controlled-drugs-list--2/list-of-most-commonly-encountered-drugs-currently-controlled-under-the-misuse-of-drugs-legislation}}</ref>
*'''United States''': Clonazepam is a Schedule IV substance.{{citation needed}}
*'''United States''': Clonazepam is a Schedule IV substance.{{citation needed}}
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Clonazepam has an elimination half-life of 30 – 40 hours[5], and is considered to be a long-acting benzodiazepine. Clonazepam has rapid onset of action, with a peak blood level occurring one to four hours after oral administration.
It's worth noting that the sudden discontinuation of benzodiazepines can be potentially life-threatening for individuals using regularly for extended periods of time.[6] It is highly recommended to taper one's dose by gradually lowering the amount taken each day for a prolonged period of time instead of stopping abruptly.[7] Not doing so can lead to serious health problems and even death.
Clonazepam is a drug of the benzodiazepine class. Benzodiazepine drugs contain a benzene ring fused to a diazepine ring, which is a seven membered ring with the two nitrogen constituents located at R1 and R4. The benzyl ring of clonazepam is substituted at R8 with a nitro group, NO2-. Further, the diazepine ring is bonded at R5 to a 2-chlorinated phenyl ring. Clonazepam also contains an oxygen group double bonded to R2 of its diazepine ring to form a ketone. This oxygen substitution at R2 is shared with other benzodiazepine drugs with the suffix -azepam.
Pharmacology
Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter gamma aminobutyric acid (GABA) by acting on its receptors.[8] As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming effects) of clonazepam on the nervous system.
The anticonvulsant properties of benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.[9]
Subjective effects
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWikicontributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Physical effects
Sedation - In terms of energy level alterations, this drug has the potential to be extremely sedating and often results in an overwhelmingly lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness.
Physical euphoria - Clonazepam is similar to alprazolam, where despite suppressing emotion, people report moderate-strong feelings of relaxation, pleasure and comfort in the body. This seems to present itself more often in those with pre-existing anxiety. However, this isn't consistent with everyone, with some users reporting no euphoric qualities at all.
Paradoxical reactions to benzodiazepines such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%).[10][11]
These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.[12]
Cognitive effects
The cognitive effects of clonazepam can be broken down into several components which progressively intensify proportional to dosage. The general head space of clonazepam is described by many as one of intense relaxation, anxiety suppression and decreased inhibition. It contains a large number of typical depressants cognitive effects.
The most prominent of these cognitive effects generally include:
Delusions of sobriety - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others. It most commonly occurs at heavy dosages.
Emotion suppression - Although this compound primarily suppresses anxiety, it also dulls other emotions in a manner which is distinct but less intensive than that of antipsychotics.
Rebound anxiety - Rebound anxiety is a commonly observed effect with anxiety relieving substances like benzodiazepines. It typically corresponds to the total duration spent under the substance's influence along with the total amount consumed in a given period, an effect which can easily lend itself to cycles of dependence and addiction.
Residual sleepiness - While benzodiazepines can be used as an effective sleep-inducing aid, their effects may persist into the morning afterward, which may lead users to feeling "groggy" or "dull" for up to a few hours.
Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.[14]
Clonazepam has a low toxicity relative to dose.[15] However, it is [[Toxicity::potentially lethal when mixed with depressants like alcohol or opioids]].
Clonazepam is extremely physically and psychologically addictive.
Tolerance will develop to the sedative-hypnotic effects within a couple of days of continuous use. After cessation, the tolerance returns to baseline in 7 - 14 days. However, in certain cases this may take significantly longer in a manner which is proportional to the duration and intensity of one's long-term usage.
Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction. For more information on tapering from benzodiazepines in a controlled manner, please see this guide.
Benzodiazepine discontinuation is notoriously difficult; it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of hypertension, seizures, and death.[6] Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.
Clonazepam presents cross-tolerance with [[Cross-tolerance::all benzodiazepines]], meaning that after its consumption all benzodiazepines will have a reduced effect.
Overdose
Benzodiazepine overdose may occur when a benzodiazepine is taken in extremely heavy quantities or concurrently with other depressants. This is particularly dangerous with other GABAergic depressants such as barbiturates and alcohol since they work in a similar fashion, but bind to distinct allosteric sites on the GABAA receptor, thus their effects potentiate one another. Benzodiazepines increase the frequency in which the chlorine ion pore opens on the GABAA receptor while barbiturates increase the duration in which they are open, meaning when both are consumed, the ion pore will open more frequently and stay open longer[16]. Benzodiazepine overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly and properly.
Symptoms of a benzodiazepine overdose may include severe thought deceleration, slurred speech, confusion, delusions, respiratory depression, coma or death. Benzodiazepine overdoses may be treated effectively in a hospital environment, with generally favorable outcomes. Benzodiazepine overdoses are sometimes treated with flumazenil, a GABAA antagonist[17], however care is primarily supportive in nature.
Dangerous interactions
Warning:Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
Dissociatives - This combination can unpredictably potentiate the amnesia, sedation, motor control loss and delusions that can be caused by each other. It may also result in a sudden loss of consciousness accompanied by a dangerous degree of respiratory depression. If nausea or vomiting occurs before consciousness is lost, users should attempt to fall asleep in the recovery position or have a friend move them into it.
Stimulants - Stimulants mask the sedative effect of depressants, which is the main factor most people use to gauge their level of intoxication. Once the stimulant effects wear off, the effects of the depressant will significantly increase, leading to intensified disinhibition, motor control loss, and dangerous black-out states. This combination can also potentially result in severe dehydration if one's fluid intake is not closely monitored. If choosing to combine these substances, one should strictly limit themselves to a pre-set schedule of dosing only a certain amount per hour until a maximum threshold has been reached.
Legal status
Internationally, clonazepam is included under the United Nations Convention on Psychotropic Substances in Schedule IV.[18]
Australia: Clonazepam is available by prescription only.[citation needed]
Brazil: Clonazepam is a "black stripe" drug, which are available by prescription only.[19]
Czech Republic: Clonazepam is a Schedule IV [20] (List 7) substance. Sold exclusively by prescription "without a blue stripe" (§ 1, g), 2. of Nařízení vlády č. 463/2013 Sb.). [21]
Germany: Clonazepam is controlled under Anlage III BtMG (Narcotics Act, Schedule III) as of August 1, 1986.[22] It can only be prescribed on a narcotic prescription form, except preparations which contain up to 2 mg clonazepam in each dosage form and solutions that contain up to 0.25% and under 250 mg clonazepam in total per packaging unit.[23]
↑Cowen, P. J., Green, A. R., Nutt, D. J. (5 March 1981). "Ethyl beta-carboline carboxylate lowers seizure threshold and antagonizes flurazepam-induced sedation in rats". Nature. 290 (5801): 54–55. doi:10.1038/290054a0. ISSN0028-0836.
↑ 6.06.1Lann, M. A., Molina, D. K. (June 2009). "A fatal case of benzodiazepine withdrawal". The American Journal of Forensic Medicine and Pathology. 30 (2): 177–179. doi:10.1097/PAF.0b013e3181875aa0. ISSN1533-404X.
↑Kahan, M., Mailis-Gagnon, A., Tunks, E. (June 2011). "Canadian guideline for safe and effective use of opioids for chronic non-cancer pain: implications for pain physicians". Pain Research & Management. 16 (3): 157–158. doi:10.1155/2011/434298. ISSN1203-6765.
↑McLean, M. J., Macdonald, R. L. (February 1988). "Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture". The Journal of Pharmacology and Experimental Therapeutics. 244 (2): 789–795. ISSN0022-3565.
↑Saïas, T., Gallarda, T. (September 2008). "[Paradoxical aggressive reactions to benzodiazepine use: a review]". L’Encephale. 34 (4): 330–336. doi:10.1016/j.encep.2007.05.005. ISSN0013-7006.
↑Twyman, R. E., Rogers, C. J., Macdonald, R. L. (March 1989). "Differential regulation of gamma-aminobutyric acid receptor channels by diazepam and phenobarbital". Annals of Neurology. 25 (3): 213–220. doi:10.1002/ana.410250302. ISSN0364-5134.
↑Hoffman, E. J., Warren, E. W. (September 1993). "Flumazenil: a benzodiazepine antagonist". Clinical Pharmacy. 12 (9): 641–656; quiz 699–701. ISSN0278-2677.
