Alprazolam

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Death may result when benzodiazepines are combined with other depressants such as opiates, barbiturates, gabapentinoids, thienodiazepines, alcohol or other GABAergic substances.[1]

It is strongly discouraged to combine these substances, particularly in common to heavy doses.

Summary sheet: Alprazolam
Alprazolam
Alprazolam.svg
Chemical Nomenclature
Common names Xanax, Alprazolam
Substitutive name Alprazolam
Systematic name 8-Chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
Class Membership
Psychoactive class Depressant
Chemical class Benzodiazepine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Threshold 0.10 - 0.25 mg
Light 0.25 - 0.5 mg
Common 0.5 - 1.5 mg
Strong 1.5 - 2 mg
Heavy 2 - 3 mg +
Duration
Total 5 - 8 hours
Onset 20 - 40 minutes
Peak 1 - 2 hours
Offset 2 - 6 hours
After effects 6 - 24 hours









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.


Alprazolam (also known as Xanax) is a depressant substance of the benzodiazepine class. Its characteristic effects include anxiety suppression, sedation, disinhibition, and muscle relaxation.[2]

Like other benzodiazepines, alprazolam binds to specific sites on the GABAA receptor.[3] It is commonly used for the medical treatment of panic disorder, generalized anxiety disorder (GAD), or social anxiety disorder (SAD).[4]

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.[5][6] Peak benefits achieved for generalized anxiety disorder (GAD) may take up to a week.[7]

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.[8] 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.[9]

Xanax (Alprazolam) 2 mg tri-score tablets

Chemistry

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".

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.[10] 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.[11]

Alprazolam causes a marked suppression of the hypothalamicpituitary-adrenal axis. Administration of alprazolam has been demonstrated to elicit an increase in striatal dopamine concentrations.[12]

Subjective effects

The general head space of alprazolam is described by many as one of intense sedation, relaxation, anxiety suppression and decreased inhibition.

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. These effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
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Visual effects
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Paradoxical effects
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Cognitive effects
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After effects
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Experience reports

There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

Toxicity and harm potential

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This toxicity and harm potential section is a stub.

As such, it may contain incomplete or even dangerously wrong information. You can help by expanding or correcting it.
We also recommend that you conduct independent research and use harm reduction practices when using this substance.

Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.[18]

Alprazolam has a low toxicity relative to dose.[19] However, it is potentially lethal when mixed with depressants like alcohol or opioids.

It is strongly recommended that one use harm reduction practices when using this substance.

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.[20] 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 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[21] 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.[22] 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

Although many psychoactive substances are reasonably safe to use on their own, they can quickly become dangerous or even life-threatening when taken with other substances. The following lists some known dangerous combinations, but cannot be guaranteed to include all of them. Independent research should always be conducted to ensure that a combination of two or more substances is safe to consume. Some interactions listed have been sourced from Tripsit.

  • Stimulants - It can be dangerous to combine depressants with stimulants due to the risk of accidental excessive intoxication. 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

  • International: Alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.[23]
  • 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.[24]
  • 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 listed in Anlage III of the BtMG, it is only legal when recieved with a narcotic prescription form.[25]
  • Ireland: Alprazolam is a Schedule 4 medicine.[26]
  • 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).[27][28]
  • Sweden: Alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).[29]
  • The Netherlands: Alprazolam is a List 2 substance of the Opium Law and is available for prescription.[citation needed]
  • United Kingdom: Alprazolam is a Class C drug under the UK drug misuse classification system. It can be obtained as a private prescription, but not through the NHS.[30]
  • United States: Alprazolam is a prescription medication assigned to Schedule IV of the Controlled Substances Act by the DEA.[31]

See also

External links

Further reading

  • The Ashton Manual - Useful information on safe withdrawal from long-term benzodiazepine use and dependence

References

  1. Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
  2. Benzodiazepine Metabolism: An Analytical Perspective" (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303399/
  4. FDA approved labeling for Xanax revision 08/23/2011 | http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018276s045lbl.pdf
  5. Pharmacokinetics and Pharmacodynamics of Alprazolam after Oral and IV Administration (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6152055
  6. 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
  7. 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
  8. A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812
  9. 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
  10. Benzodiazepine interactions with GABA receptors (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6147796
  11. 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
  12. 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
  13. http://www.ncbi.nlm.nih.gov/pubmed/18922233 | Saïas T, Gallarda T | Paradoxical aggressive reactions to benzodiazepine use: a review
  14. Paton C | Benzodiazepines and disinhibition: a review | Psychiatr Bull R Coll Psychiatr | http://pb.rcpsych.org/cgi/reprint/26/12/460.pdf
  15. Bond AJ | Drug-induced behavioural disinhibition: incidence, mechanisms and therapeutic implications | CNS Drugs
  16. Drummer OH | Benzodiazepines—effects on human performance and behavior | Forensic Sci Rev
  17. Goyal, Sarita. "Drugs and Dreams." Indian Journal of Clinical Practice (n.d.): n. pag. Web. | http://medind.nic.in/iaa/t13/i3/iaat13i3p624.pdf
  18. Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644
  19. Benzodiazepine metabolism: an analytical perspective (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614
  20. Principles and Practice of Psychopharmacotherapy | http://books.google.com/books?id=_ePK9wwcQUMC&pg=PA535
  21. Amrein, R., Leishman, B., Bentzinger, C., & Roncari, G. (1987). Flumazenil in benzodiazepine antagonism. Medical Toxicology and Adverse Drug Experience, 2(6), 411-429. PMID: 8306565
  22. A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812
  23. List of Psychotropic Substances under International Control | http://www.incb.org/documents/Psychotropics/green_lists/Green_list_ENG_2014_85222_GHB.pdf
  24. Alprazolam to be rescheduled from next year | http://www.australiandoctor.com.au/news/latest-news/alprazolam-to-be-rescheduled-from-next-year
  25. https://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html
  26. Misuse Of Drugs (Amendment) Regulations | http://www.irishstatutebook.ie/1993/en/si/0342.html
  27. Tabella IV Sostanze stupefacenti http://www.salute.gov.it/imgs/C_17_pagineAree_3729_listaFile_itemName_3_file.pdf
  28. Tabella Medicinali D.P.R. 309/90 http://www.salute.gov.it/imgs/C_17_pagineAree_3729_listaFile_itemName_4_file.xls
  29. "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
  30. Misuse of Drugs Act 1971 (c. 38) | http://www.legislation.gov.uk/ukpga/1971/38/schedules
  31. DEA, Drug Scheduling | http://www.deadiversion.usdoj.gov/schedules/index.html