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Alprazolam: Difference between revisions
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Like other [[benzodiazepines]], alprazolam binds to specific sites on the [[gamma-amino-butyric acid|GABA<sub>A</sub>]] receptor.<ref>{{cite journal | vauthors=((Nuss, P.)) | journal=Neuropsychiatric Disease and Treatment | title=Anxiety disorders and GABA neurotransmission: a disturbance of modulation | volume=11 | pages=165–175 | date=17 January 2015 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303399/ | issn=1176-6328 | doi=10.2147/NDT.S58841}}</ref> It is commonly used for the medical treatment of panic disorder, generalized anxiety disorder (GAD), or social anxiety disorder (SAD).<ref>FDA approved labeling for Xanax revision 08/23/2011 | http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018276s045lbl.pdf</ref> | Like other [[benzodiazepines]], alprazolam binds to specific sites on the [[gamma-amino-butyric acid|GABA<sub>A</sub>]] receptor.<ref>{{cite journal | vauthors=((Nuss, P.)) | journal=Neuropsychiatric Disease and Treatment | title=Anxiety disorders and GABA neurotransmission: a disturbance of modulation | volume=11 | pages=165–175 | date=17 January 2015 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303399/ | issn=1176-6328 | doi=10.2147/NDT.S58841}}</ref> It is commonly used for the medical treatment of panic disorder, generalized anxiety disorder (GAD), or social anxiety disorder (SAD).<ref>FDA approved labeling for Xanax revision 08/23/2011 | http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018276s045lbl.pdf</ref> | ||
Alprazolam has a fast onset of action and symptomatic relief. | Alprazolam has a fast onset of action and symptomatic relief. 90% of peak effects are achieved within the 1st hour of using in preparation for panic disorder and full peak effects are achieved in 1.5 and 1.6 hours respectively.<ref>{{cite journal | vauthors=((Smith, R. B.)), ((Kroboth, P. D.)), ((Vanderlugt, J. T.)), ((Phillips, J. P.)), ((Juhl, R. P.)) | journal=Psychopharmacology | title=Pharmacokinetics and pharmacodynamics of alprazolam after oral and IV administration | volume=84 | issue=4 | pages=452–456 | date= 1984 | issn=0033-3158 | doi=10.1007/BF00431449}}</ref><ref>{{cite journal | vauthors=((Sheehan, D. V.)), ((Sheehan, K. H.)), ((Raj, B. A.)) | journal=Psychopharmacology Bulletin | title=The speed of onset of action of alprazolam-XR compared to alprazolam-CT in panic disorder | volume=40 | issue=2 | pages=63–81 | date= 2007 | issn=0048-5764}}</ref> Peak benefits achieved for GAD may take up to a week.<ref>{{cite journal | vauthors=((Verster, J. C.)), ((Volkerts, E. R.)) | journal=CNS Drug Reviews | title=Clinical Pharmacology, Clinical Efficacy, and Behavioral Toxicity of Alprazolam: A Review of the Literature | volume=10 | issue=1 | pages=45–76 | date=7 June 2006 | url=https://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2004.tb00003.x | issn=1080563X | doi=10.1111/j.1527-3458.2004.tb00003.x}}</ref> | ||
The [[Benzodiazepine#Discontinuation|sudden discontinuation of benzodiazepines]] can be potentially dangerous or life-threatening for individuals using regularly for extended periods of time, sometimes resulting in seizures or death.<ref>{{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.)), ((Wilson, L.)), ((Mailis-Gagnon, A.)), ((Srivastava, A.)) | journal=Canadian Family Physician | title=Canadian guideline for safe and effective use of opioids for chronic noncancer pain. Appendix B-6: Benzodiazepine Tapering | volume=57 | issue=11 | pages=1269–1276 | date= November 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215603/ | issn=0008-350X}}</ref> | The [[Benzodiazepine#Discontinuation|sudden discontinuation of benzodiazepines]] can be potentially dangerous or life-threatening for individuals using regularly for extended periods of time, sometimes resulting in seizures or death.<ref>{{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.)), ((Wilson, L.)), ((Mailis-Gagnon, A.)), ((Srivastava, A.)) | journal=Canadian Family Physician | title=Canadian guideline for safe and effective use of opioids for chronic noncancer pain. Appendix B-6: Benzodiazepine Tapering | volume=57 | issue=11 | pages=1269–1276 | date= November 2011 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215603/ | issn=0008-350X}}</ref> | ||
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The GABA<sub>A</sub> receptor is made up of 5 subunits out of a possible 19, and GABA<sub>A</sub> receptors made up of different combinations of subunits have different properties, different locations within the brain, and, importantly, different activities with regard to benzodiazepines. Alprazolam and other triazolobenzodiazepines such as triazolam that have a triazole ring fused to their diazepine ring appear to have antidepressant properties.<ref>{{cite journal | vauthors=((Barbee, J. G.)) | journal=The Journal of Clinical Psychiatry | title=Memory, benzodiazepines, and anxiety: integration of theoretical and clinical perspectives | volume=54 Suppl | pages=86–97; discussion 98-101 | date= October 1993 | issn=0160-6689}}</ref> This is perhaps due to the similarities shared with tricyclic antidepressants, as they have two benzene rings fused to a diazepine ring. The therapeutic properties of alprazolam are similar to other benzodiazepines and include anxiolytic, anticonvulsant, muscle relaxant, hypnotic and amnesic; however, it is used mainly as an anxiolytic. | The GABA<sub>A</sub> receptor is made up of 5 subunits out of a possible 19, and GABA<sub>A</sub> receptors made up of different combinations of subunits have different properties, different locations within the brain, and, importantly, different activities with regard to benzodiazepines. Alprazolam and other triazolobenzodiazepines such as triazolam that have a triazole ring fused to their diazepine ring appear to have antidepressant properties.<ref>{{cite journal | vauthors=((Barbee, J. G.)) | journal=The Journal of Clinical Psychiatry | title=Memory, benzodiazepines, and anxiety: integration of theoretical and clinical perspectives | volume=54 Suppl | pages=86–97; discussion 98-101 | date= October 1993 | issn=0160-6689}}</ref> This is perhaps due to the similarities shared with tricyclic antidepressants, as they have two benzene rings fused to a diazepine ring. The therapeutic properties of alprazolam are similar to other benzodiazepines and include anxiolytic, anticonvulsant, muscle relaxant, hypnotic and amnesic; however, it is used mainly as an anxiolytic. | ||
Giving alprazolam, as compared to lorazepam, has been demonstrated to elicit a statistically significant increase in extracellular dopamine D1 and D2 concentrations in the striatum.<ref name="Bentue-Ferrer2001"/> | Giving alprazolam, as compared to lorazepam, has been demonstrated to elicit a statistically significant increase in extracellular dopamine D1 and D2 concentrations in the striatum.<ref name="Bentue-Ferrer2001" /> | ||
==Subjective effects== | ==Subjective effects== | ||
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{{Preamble/SubjectiveEffects}} | {{Preamble/SubjectiveEffects}} | ||
{{effects/base | {{effects/base | ||
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*'''[[Effect::Dizziness]]'''{{citation needed}} - Dizziness is sometimes present with higher doses, although generally less than the dizzying effects of alcohol (colloquially known as "the spins"). | *'''[[Effect::Dizziness]]'''{{citation needed}} - Dizziness is sometimes present with higher doses, although generally less than the dizzying effects of alcohol (colloquially known as "the spins"). | ||
*'''[[Effect::Seizure suppression]]'''{{citation needed}} - Alprazolam has seizure suppressing properties as a result of its [[GABA|GABA-mediated]] inhibitory effects on the nervous system. | *'''[[Effect::Seizure suppression]]'''{{citation needed}} - Alprazolam has seizure suppressing properties as a result of its [[GABA|GABA-mediated]] inhibitory effects on the nervous system. | ||
*'''[[Effect::Dry mouth]]''' - Although infrequent, Alprazolam is capable of causing a dry mouth in some users. This may make a user drink more water. This is not the same as dehydration, as it is not known to be dangerous.<ref>Elie R, Lamontagne Y (June 1984). "Alprazolam and diazepam in the treatment of generalized anxiety". Journal of Clinical Psychopharmacology. 4 (3): 125–9. https://journals.lww.com/psychopharmacology/abstract/1984/06000/alprazolam_and_diazepam_in_the_treatment_of.2.aspx</ref> | |||
}} | }} | ||
{{effects/cognitive| | {{effects/cognitive| | ||
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*'''[[Effect::Sleepiness]]''' | *'''[[Effect::Sleepiness]]''' | ||
*'''[[Effect::Thought deceleration]]''' | *'''[[Effect::Thought deceleration]]''' | ||
}} | }} | ||
|{{effects/visual| | |{{effects/visual| | ||
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{{toxicity}} | {{toxicity}} | ||
[[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>]] | [[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>]] | ||
Alprazolam has a [[Toxicity::low toxicity]] relative to dose.<ref name="Mandroili2008"/> However, it is [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[ | Alprazolam has a [[Toxicity::low toxicity]] relative to dose.<ref name="Mandroili2008" /> However, it is [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]], [[opioids]], or [[barbiturates]]]]. Resulting in increased [[Respiratory depression|respiratory depression]] via a synergistic effect.<ref>Weaver MF. Prescription Sedative Misuse and Abuse. Yale J Biol Med. 2015 Sep;88(3):247-56. [[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553644/ PMC free article]] [[https://pubmed.ncbi.nlm.nih.gov/26339207 PubMed]] </ref> | ||
It is strongly recommended that one use [[harm reduction practices]] when using this substance. | It is strongly recommended that one use [[harm reduction practices]] when using this substance. | ||
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*'''Australia''': Alprazolam was originally a Schedule 4 (prescription only) medication; however, as of January 2014, it will become a Schedule 8 medication, subjecting it to more rigorous prescribing requirements.<ref>Alprazolam to be rescheduled from next year | http://www.australiandoctor.com.au/news/latest-news/alprazolam-to-be-rescheduled-from-next-year</ref> | *'''Australia''': Alprazolam was originally a Schedule 4 (prescription only) medication; however, as of January 2014, it will become a Schedule 8 medication, subjecting it to more rigorous prescribing requirements.<ref>Alprazolam to be rescheduled from next year | http://www.australiandoctor.com.au/news/latest-news/alprazolam-to-be-rescheduled-from-next-year</ref> | ||
*'''Austria''': Alprazolam is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich).{{citation needed}} | *'''Austria''': Alprazolam is legal for medical use under the AMG (Arzneimittelgesetz Österreich) and illegal when sold or possessed without a prescription under the SMG (Suchtmittelgesetz Österreich).{{citation needed}} | ||
*'''Germany''': Alprazolam 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 1 mg | *'''Czechia''': Alprazolam 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 with a prescription "without a blue stripe" (§ 1, g), 1. of ''Nařízení vlády č. 463/2013 Sb.'') <ref>https://www.zakonyprolidi.cz/cs/2013-463</ref> | ||
*'''France''': Alprazolam is a List I substance and is available for prescription.<ref>https://www.vidal.fr/medicaments/gammes/alprazolam-biogaran-11672.html</ref> It is illegal to buy without a prescription. | |||
*'''Germany''': Alprazolam 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 1 mg alprazolam in each dosage form.<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> | |||
*'''Ireland''': Alprazolam is a Schedule 4 medicine.<ref>{{Citation | vauthors=((eISB)) | title=Misuse Of Drugs (Amendment) Regulations | url=https://www.irishstatutebook.ie/eli/1993/si/342/made/en/print}}</ref> | *'''Ireland''': Alprazolam is a Schedule 4 medicine.<ref>{{Citation | vauthors=((eISB)) | title=Misuse Of Drugs (Amendment) Regulations | url=https://www.irishstatutebook.ie/eli/1993/si/342/made/en/print}}</ref> | ||
*'''Italy''': Alprazolam is a schedule IV drug (Tabella 4) of the "Testo unico sulla droga (D.P.R. 309/90)". When prescribed for medical use it falls under Pharmaceuticals section B and E (Tabella medicinali sezione B ed E).<ref>Tabella IV Sostanze stupefacenti http://www.salute.gov.it/imgs/C_17_pagineAree_3729_listaFile_itemName_3_file.pdf</ref><ref>Tabella Medicinali D.P.R. 309/90 http://www.salute.gov.it/imgs/C_17_pagineAree_3729_listaFile_itemName_4_file.xls</ref> | *'''Italy''': Alprazolam is a schedule IV drug (Tabella 4) of the "Testo unico sulla droga (D.P.R. 309/90)". When prescribed for medical use it falls under Pharmaceuticals section B and E (Tabella medicinali sezione B ed E).<ref>Tabella IV Sostanze stupefacenti http://www.salute.gov.it/imgs/C_17_pagineAree_3729_listaFile_itemName_3_file.pdf</ref><ref>Tabella Medicinali D.P.R. 309/90 http://www.salute.gov.it/imgs/C_17_pagineAree_3729_listaFile_itemName_4_file.xls</ref> | ||
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*'''Switzerland''': Alprazolam 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''': Alprazolam 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''': Alprazolam 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''': Alprazolam 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}} | ||
*'''The Netherlands''': Alprazolam is a List 2 substance of the Opium Law and is available for prescription.{{citation needed}} | *'''The Netherlands''': Alprazolam is a List 2 substance of the Opium Law<ref>{{Citation|title=Opiumwet, Lijst II (Dutch) | year=2023|url=https://wetten.overheid.nl/BWBR0001941/2023-09-12#BijlageII}}</ref> and is available for prescription.{{citation needed}} | ||
*'''United Kingdom''': Alprazolam is classified as a controlled drug and listed under Schedule IV, Part I (CD Benz POM) of the Misuse of Drugs Regulations 2001, allowing possession with a valid prescription. The Misuse of Drugs Act 1971 makes it illegal to possess the drug without a prescription and, for such purposes, it is classified as a Class C drug.<ref>{{Citation | title=Drugs licensing | url=https://www.gov.uk/government/collections/drugs-licensing}}</ref> | *'''United Kingdom''': Alprazolam is classified as a controlled drug and listed under Schedule IV, Part I (CD Benz POM) of the Misuse of Drugs Regulations 2001, allowing possession with a valid prescription. The Misuse of Drugs Act 1971 makes it illegal to possess the drug without a prescription and, for such purposes, it is classified as a Class C drug.<ref>{{Citation | title=Drugs licensing | url=https://www.gov.uk/government/collections/drugs-licensing}}</ref> | ||
*'''United States''': Alprazolam is a prescription medication assigned to Schedule IV of the Controlled Substances Act by the DEA.<ref>DEA, Drug Scheduling | http://www.deadiversion.usdoj.gov/schedules/index.html</ref> | *'''United States''': Alprazolam is a prescription medication assigned to Schedule IV of the Controlled Substances Act by the DEA.<ref>DEA, Drug Scheduling | http://www.deadiversion.usdoj.gov/schedules/index.html</ref> | ||
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*[https://erowid.org/pharms/alprazolam/alprazolam.shtml Alprazolam (Erowid Vault)] | *[https://erowid.org/pharms/alprazolam/alprazolam.shtml Alprazolam (Erowid Vault)] | ||
*[https://isomerdesign.com/PiHKAL/explore.php?id=3001 Alprazolam (Isomer Design)] | *[https://isomerdesign.com/PiHKAL/explore.php?id=3001 Alprazolam (Isomer Design)] | ||
*[https://go.drugbank.com/drugs/DB00404 Alprazolam (DrugBank)] | |||
*[https://www.drugs.com/alprazolam.html Alprazolam (Drugs.com)] | |||
*[https://drugs-forum.com/wiki/Alprazolam Alprazolam (Drugs-Forum)] | |||
==Further reading== | ==Further reading== | ||