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'''Alprazolam''' (also known as '''Xanax''') is a [[chemical class::depressant]] substance of the [[Chemical class::benzodiazepine]] class. Its characteristic effects include [[anxiety suppression]], [[sedation]], [[disinhibition]], and [[muscle relaxation]].<ref>Benzodiazepine Metabolism: An Analytical Perspective" (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614</ref>
'''Alprazolam''' (also known as '''Xanax''') is a [[psychoactive class::depressant]] substance of the [[Chemical class::benzodiazepine]] class. Its characteristic effects include [[anxiety suppression]], [[sedation]], [[disinhibition]], and [[muscle relaxation]].<ref name="Mandroili2008">{{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 | date= October 2008 | issn=1389-2002 | doi=10.2174/138920008786049258}}</ref>
Like other [[benzodiazepines]], alprazolam binds to specific sites on the [[gamma-amino-butyric acid|GABA<sub>A</sub>]] receptor.<ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303399/</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. Ninety percent of peak effects are achieved within the first hour of using in preparation for panic disorder and full peak effects are achieved in 1.5 and 1.6 hours respectively.<ref>Pharmacokinetics and Pharmacodynamics of Alprazolam after Oral and IV Administration (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6152055</ref><ref>The Speed of Onset of Action of Alprazolam-XR Compared to Alprazolam-CT in Panic Disorder (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17514187</ref> Peak benefits achieved for generalized anxiety disorder (GAD) may take up to a week.<ref>Clinical Pharmacology, Clinical Efficacy, and Behavioral Toxicity of Alprazolam: A Review of the Literature | http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2004.tb00003.x/pdf</ref>
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>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>
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>
Alprazolam 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 alprazolam is substituted at R<sub>8</sub> with a chlorine group. Further, the diazepine ring is bonded at R<sub>5</sub> to a phenyl ring. Alprazolam also contains a 1-methylated triazole ring fused to and incorporating R<sub>1</sub> and R<sub>2</sub> of its diazepine ring. Alprazolam belongs to a class of benzodiazepines containing this fused triazole ring, called triazolobenzodiazepines, distinguished by the suffix "-zolam".
Alprazolam 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 alprazolam is substituted at R<sub>8</sub> with a chlorine group. Further, the diazepine ring is bonded at R<sub>5</sub> to a phenyl ring. Alprazolam also contains a 1-methylated triazole ring fused to and incorporating R<sub>1</sub> and R<sub>2</sub> of its diazepine ring. Alprazolam belongs to a class of benzodiazepines containing this fused triazole ring, called triazolobenzodiazepines, distinguished by the suffix "-zolam".
Alprazolam is substituted with a phenyl group at position 6, with a chlorine atom at position 8 and with a methyl group at position 1. It is an analogue of triazolam, the difference between them being the absence of a chlorine atom in the 'ortho' position of the phenyl ring. It is soluble in alcohol and insoluble in water.
==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 [[receptors]].<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 alprazolam 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 [[receptors]].<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> Alprazolam is a positive allosteric modulator of the gamma-aminobutyric acid (GABA) type A receptor. 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 alprazolam 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>{{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>
Alprazolam causes a marked suppression of the hypothalamic-pituitary-adrenal axis. Administration of alprazolam has been demonstrated to elicit an increase in striatal [[dopamine]] concentrations.<ref name="Bentue-Ferrer2001">{{cite journal | vauthors=((Bentué-Ferrer, D.)), ((Reymann, J. M.)), ((Tribut, O.)), ((Allain, H.)), ((Vasar, E.)), ((Bourin, M.)) | journal=European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology | title=Role of dopaminergic and serotonergic systems on behavioral stimulatory effects of low-dose alprazolam and lorazepam | volume=11 | issue=1 | pages=41–50 | date= February 2001 | issn=0924-977X | doi=10.1016/s0924-977x(00)00137-1}}</ref> This results in effects including reduced anxiety, muscle relaxant, antidepressant and anticonvulsant activity. The GABA chemical and receptor system mediates inhibitory or calming effects of alprazolam on the nervous system. Binding of alprazolam to the GABA<sub>A</sub> receptor, a chloride ion channel, enhances the effects of GABA, a neurotransmitter. When GABA binds the GABA<sub>A</sub> receptor the channel opens and chloride enters the cell which makes it more resistant to depolarization. Therefore, alprazolam has a depressant effect on synaptic transmission to reduce anxiety.<ref>{{cite book | vauthors=((Hitchings, A.)), ((Lonsdale, D.)), ((Burrage, D.)), ((Baker, E.)) | date= 2014 | title=Top 100 drugs: clinical pharmacology and practical prescribing | publisher=Churchill Livingstone | isbn=9780702055164}}</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>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 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.
Alprazolam causes a marked suppression of the hypothalamicpituitary-adrenal axis. Administration of alprazolam has been demonstrated to elicit an increase in striatal [[dopamine]] concentrations.<ref>Role of dopaminergic and serotonergic systems on behavioral stimulatory effects of low-dose alprazolam and lorazepam (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/11226811</ref>
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/visual|
{{effects/cognitive|
*'''[[Effect::Visual acuity suppression]]''' - Like many [[depressants]], alprazolam is known to cause blurred or otherwise suppressed visual acuity.
}}
{{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><p>
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></p>
}}
|{{effects/cognitive|
*'''[[Effect::Analysis suppression]]'''
*'''[[Effect::Analysis suppression]]'''
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*'''[[Effect::Sleepiness]]'''
*'''[[Effect::Sleepiness]]'''
*'''[[Effect::Thought deceleration]]'''
*'''[[Effect::Thought deceleration]]'''
}}
|{{effects/visual|
*'''[[Effect::Visual acuity suppression]]''' - Like many [[depressants]], alprazolam is known to cause blurred or otherwise suppressed visual acuity.
}}
}}
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*'''[[Effect::Thought disorganization]]'''
*'''[[Effect::Thought disorganization]]'''
*'''[[Effect::Irritability]]'''
*'''[[Effect::Irritability]]'''
}}
{{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>{{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> <p>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><ref>{{cite journal | vauthors=((Drummer, O. H.)) | journal=Forensic Science Review | title=Benzodiazepines - Effects on Human Performance and Behavior | volume=14 | issue=1–2 | pages=1–14 | date= February 2002 | issn=1042-7201}}</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>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>]]
Alprazolam has a [[Toxicity::low toxicity]] relative to dose.<ref>Benzodiazepine metabolism: an analytical perspective (PubMed.gov / NCBI) | 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]]]].
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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Alprazolam is [[Addiction potential::extremely physically and psychologically addictive]].
Alprazolam is [[Addiction potential::extremely physically and psychologically addictive]].
Tolerance will develop to the sedative-hypnotic effects [[Time to full tolerance::within a couple of days of continuous use]].<ref>Principles and Practice of Psychopharmacotherapy | http://books.google.com/books?id=_ePK9wwcQUMC&pg=PA535</ref> After cessation, the tolerance returns to baseline in [[Time to zero tolerance::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.
Tolerance will develop to the sedative-hypnotic effects [[Time to full tolerance::within a couple of days of continuous use]].<ref>{{cite book | vauthors=((Janicak, P. G.)), ((Marder, S. R.)), ((Pavuluri, M. N.)) | date=25 October 2010 | title=Principles and Practice of Psychopharmacotherapy | publisher=Lippincott Williams & Wilkins | isbn=9781605475653}}</ref> After cessation, the tolerance returns to baseline in [[Time to zero tolerance::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.
Alprazolam presents cross-tolerance with [[Cross-tolerance::all [[benzodiazepines]]]], meaning that after its consumption all benzodiazepines will have a reduced effect.
Alprazolam presents cross-tolerance with [[Cross-tolerance::all [[benzodiazepines]]]], meaning that after its consumption all benzodiazepines will have a reduced effect.
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==Legal status==
==Legal status==
Internationally, alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.<ref>List of Psychotropic Substances under International Control | http://www.incb.org/documents/Psychotropics/green_lists/Green_list_ENG_2014_85222_GHB.pdf</ref>
Internationally, alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.<ref>List of Psychotropic Substances under International Control | http://www.incb.org/documents/Psychotropics/green_lists/Green_list_ENG_2014_85222_GHB.pdf</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}}
*'''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>
*'''Germany:''' Alprazolam is listed in Anlage III of the BtMG, meaning it is only legal when received with a narcotic prescription form.<ref>https://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html</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}}
*'''Ireland:''' Alprazolam is a Schedule 4 medicine.<ref>Misuse Of Drugs (Amendment) Regulations | http://www.irishstatutebook.ie/1993/en/si/0342.html</ref>
*'''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>
*'''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>
*'''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.
*'''Sweden:''' Alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).<ref>"Läkemedelsverkets föreskrifter (LVFS 2011:10) om förteckningar över narkotika" [Medical Products Agency on the lists of drugs] | http://www.lakemedelsverket.se/upload/lvfs/konsoliderade/LVFS_2011_10_konsoliderad_tom_2012_6.pdf</ref>
*'''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>
*'''The Netherlands:''' Alprazolam is a List 2 substance of the Opium Law and is available for prescription.{{citation needed}}
*'''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>
*'''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>https://www.gov.uk/government/publications/controlled-drugs-list</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>
*'''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>
*'''Russia''': In Russia, since 2013, alprazolam is a Schedule III controlled substance.<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>
*'''Sweden''': Alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).<ref>"Läkemedelsverkets föreskrifter (LVFS 2011:10) om förteckningar över narkotika" [Medical Products Agency on the lists of drugs] | http://www.lakemedelsverket.se/upload/lvfs/konsoliderade/LVFS_2011_10_konsoliderad_tom_2012_6.pdf</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}}
*'''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 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>
*[https://www.benzo.org.uk/manual/index.htm The Ashton Manual] - Useful information on safe withdrawal from long-term benzodiazepine use and dependence
*[https://www.benzo.org.uk/manual/index.htm The Ashton Manual] - Useful information on safe withdrawal from long-term benzodiazepine use and dependence
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.
Like other benzodiazepines, alprazolam binds to specific sites on the GABAA receptor.[4] It is commonly used for the medical treatment of panic disorder, generalized anxiety disorder (GAD), or social anxiety disorder (SAD).[5]
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.[6][7] Peak benefits achieved for GAD may take up to a week.[8]
The 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.[9] 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.[10]
Alprazolam 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 alprazolam is substituted at R8 with a chlorine group. Further, the diazepine ring is bonded at R5 to a phenyl ring. Alprazolam also contains a 1-methylated triazole ring fused to and incorporating R1 and R2 of its diazepine ring. Alprazolam belongs to a class of benzodiazepines containing this fused triazole ring, called triazolobenzodiazepines, distinguished by the suffix "-zolam".
Alprazolam is substituted with a phenyl group at position 6, with a chlorine atom at position 8 and with a methyl group at position 1. It is an analogue of triazolam, the difference between them being the absence of a chlorine atom in the 'ortho' position of the phenyl ring. It is soluble in alcohol and insoluble in water.
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.[11] Alprazolam is a positive allosteric modulator of the gamma-aminobutyric acid (GABA) type A receptor. As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming effects) of alprazolam 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.[12]
Alprazolam causes a marked suppression of the hypothalamic-pituitary-adrenal axis. Administration of alprazolam has been demonstrated to elicit an increase in striatal dopamine concentrations.[13] This results in effects including reduced anxiety, muscle relaxant, antidepressant and anticonvulsant activity. The GABA chemical and receptor system mediates inhibitory or calming effects of alprazolam on the nervous system. Binding of alprazolam to the GABAA receptor, a chloride ion channel, enhances the effects of GABA, a neurotransmitter. When GABA binds the GABAA receptor the channel opens and chloride enters the cell which makes it more resistant to depolarization. Therefore, alprazolam has a depressant effect on synaptic transmission to reduce anxiety.[14]
The GABAA receptor is made up of 5 subunits out of a possible 19, and GABAA 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.[15] 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.[13]
Subjective effects
The general head space of alprazolam is described by many as one of intense sedation, relaxation, anxiety suppression and decreased inhibition.
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[citation needed] - Alprazolam is capable of producing strong sedation and can lead to a lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and need to fight to stay awake. This sleep deprivation increases proportionally to dosage and eventually becomes powerful enough to force the user into a deep state of unconsciousness.
Perception of bodily heaviness - Alprazolam is reported to cause feelings of heaviness in the body. This effect can range from motor impairment and difficulty moving at lower doses to complete lethargy or inability to stand up or move at high doses.
Motor control loss[citation needed] - Alprazolam impairs motor control in a dose-dependent manner similar to alcohol. Higher doses significantly increase the risk of physical injury via falling over or stumbling into objects. This risk is especially prominent around stairs and slopes.
Dizziness[citation needed] - Dizziness is sometimes present with higher doses, although generally less than the dizzying effects of alcohol (colloquially known as "the spins").
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.[16]
Compulsive redosing - Alprazolam produces disinhibition which, along with its memory suppressing effects, can easily lead the user to black out and redose continually until their supply runs out or they lose consciousness. This effect can place the user at risk of fatal overdose from respiratory depression if they are consuming it with alcohol or other depressants.
Confusion - Alprazolam can cause confusion at heavy doses. This effect is a result of the drug suppressing basic cognitive functions such as comprehension, memory, and reasoning skills.
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.
Dream suppression[citation needed] - Benzodiazepines like alprazolam generally inhibit REM sleep and suppress the experience of dreaming. Sleep on benzodiazepines is generally reported to be deep and refreshing, although it should be noted that the actual sleep quality is lower which is why the use of benzodiazepines as long-term sleep aids is not advised.
Emotion suppression - Although alprazolam primarily suppresses anxiety, it also dulls other emotions in a manner which is distinct but less intensive than that of antipsychotics.
Euphoria - A distinct portion of users report feeling a marked sense of emotional well-being and comfort while under the influence of this substance. Because this does not occur regularly or consistently for most users, it is speculated that this effect only manifests among those who have unusually high baseline levels of anxiety.
Language suppression - Alprazolam is known to cause slurred speech and difficulty communicating words in a clear fashion.
Amnesia - Higher doses of alprazolam can easily lead to complete short-term amnesia (black out) similar to that of high doses of alcohol.
Motivation suppression - Due to alprazolam's heavy sedation and lethargy, doing any type of activity that requires moving, or high amounts of effort may be difficult to do, especially at higher doses.
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.
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%).[18][19]
These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.[20][21]
Experience reports
Anecdotal reports which describe the effects of this compound within our experience index include:
This toxicity and harm potential section is a stub.
As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it. Note: Always conduct independent research and use harm reduction practices if using this substance.
Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.[22]
The acute oral LD50 in rats is 331–2171 mg/kg. Other experiments in animals have indicated that cardiopulmonary collapse can occur following massive intravenous doses of alprazolam.
Dependence and abuse potential
Alprazolam is extremely physically and psychologically addictive.
Tolerance will develop to the sedative-hypnotic effects within a couple of days of continuous use.[24] 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.
Alprazolam 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 with extremely high doses or, more commonly, when it is taken with other depressants. This risk is especially present with other GABAergic depressants, such as barbiturates and alcohol, since they work in a similar fashion but bind to distinct sites on the GABAA receptor, resulting in significant cross-potentiation.[citation needed]
Benzodiazepine overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly. Symptoms may include severe slurred speech, confusion, delusions, respiratory depression, and non-responsiveness. The user might seem like they are sleepwalking. The user is also more susceptible to consume more of the same or another substance due to their impaired judgement, which is typically not seen with other substances during overdose.
Benzodiazepine overdoses may be treated effectively in a hospital environment, with generally favorable outcomes. Care is primarily supportive in nature, although overdoses are sometimes treated with flumazenil, a GABAA antagonist[25] or additional procedures such as adrenaline injections if other substances are involved.[citation needed]
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 high blood pressure, seizures, and death.[26] Substances which lower the seizure threshold such as tramadol should be avoided during withdrawal.[citation needed] Abrupt discontinuation also causes rebound stimulation which presents as anxiety, insomnia and restlessness.[citation needed]
If one wishes to discontinue after a period of regular use, it is safest to reduce the dose each day by a very small amount for a couple of weeks until close to abstinence. If using a short half-life benzodiazepine such as alprazolam or etizolam, a longer acting variety such as diazepam or clonazepam can be substituted. Symptoms may still be present, but their severity will be reduced significantly.
For more information on tapering from benzodiazepines in a controlled manner, please see this guide. Small quantities of alcohol can also help to reduce the symptoms, but otherwise cannot be used as an effective tapering agent.
The duration and severity of withdrawal symptoms depend on a number of factors including the half-life of the substance used, tolerance and the duration of abuse. Major symptoms will usually start within just a few days after discontinuation and persist for around a week for shorter lasting benzodiazepines. Benzodiazepines with longer half-lives will exhibit withdrawal symptoms with a slow onset and extended duration.[citation needed]
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, alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.[27]
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.[28]
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]
Czechia: Alprazolam is a Schedule IV [29] (List 7) substance. Sold exclusively with a prescription "without a blue stripe" (§ 1, g), 1. of Nařízení vlády č. 463/2013 Sb.) [30]
France: Alprazolam is a List I substance and is available for prescription.[31] 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.[32] It can only be prescribed on a narcotic prescription form, except preparations which contain up to 1 mg alprazolam in each dosage form.[33]
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).[35][36]
Russia: In Russia, since 2013, alprazolam is a Schedule III controlled substance.[37]
Sweden: Alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).[38]
Switzerland: Alprazolam is a controlled substance specifically named under Verzeichnis B. Medicinal use is permitted.[39]
Turkey: Alprazolam is a 'green prescription' only substance[40] and illegal when sold or possessed without a prescription.[citation needed]
The Netherlands: Alprazolam is a List 2 substance of the Opium Law[41] 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.[42]
United States: Alprazolam is a prescription medication assigned to Schedule IV of the Controlled Substances Act by the DEA.[43]
↑ 3.03.1Mandrioli, R., Mercolini, L., Raggi, M. A. (October 2008). "Benzodiazepine metabolism: an analytical perspective". Current Drug Metabolism. 9 (8): 827–844. doi:10.2174/138920008786049258. ISSN1389-2002.
↑Smith, R. B., Kroboth, P. D., Vanderlugt, J. T., Phillips, J. P., Juhl, R. P. (1984). "Pharmacokinetics and pharmacodynamics of alprazolam after oral and IV administration". Psychopharmacology. 84 (4): 452–456. doi:10.1007/BF00431449. ISSN0033-3158.
↑Sheehan, D. V., Sheehan, K. H., Raj, B. A. (2007). "The speed of onset of action of alprazolam-XR compared to alprazolam-CT in panic disorder". Psychopharmacology Bulletin. 40 (2): 63–81. ISSN0048-5764.
↑Lann, 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.
↑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.
↑ 13.013.1Bentué-Ferrer, D., Reymann, J. M., Tribut, O., Allain, H., Vasar, E., Bourin, M. (February 2001). "Role of dopaminergic and serotonergic systems on behavioral stimulatory effects of low-dose alprazolam and lorazepam". European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology. 11 (1): 41–50. doi:10.1016/s0924-977x(00)00137-1. ISSN0924-977X.
↑Hitchings, A., Lonsdale, D., Burrage, D., Baker, E. (2014). Top 100 drugs: clinical pharmacology and practical prescribing. Churchill Livingstone. ISBN9780702055164.
↑Barbee, J. G. (October 1993). "Memory, benzodiazepines, and anxiety: integration of theoretical and clinical perspectives". The Journal of Clinical Psychiatry. 54 Suppl: 86–97; discussion 98–101. ISSN0160-6689.
↑Drummer, O. H. (February 2002). "Benzodiazepines - Effects on Human Performance and Behavior". Forensic Science Review. 14 (1–2): 1–14. ISSN1042-7201.
↑Janicak, P. G., Marder, S. R., Pavuluri, M. N. (25 October 2010). Principles and Practice of Psychopharmacotherapy. Lippincott Williams & Wilkins. ISBN9781605475653.
↑Hoffman, E. J., Warren, E. W. (September 1993). "Flumazenil: a benzodiazepine antagonist". Clinical Pharmacy. 12 (9): 641–656; quiz 699–701. ISSN0278-2677.
↑Lann, 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.
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