Alprazolam

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

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

Summary sheet: Alprazolam
Alprazolam
Molecular structure of 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 (trade name Xanax) is a short-acting psychoactive drug of the benzodiazepine class which produces anxiolytic, sedative, hypnotic, muscle relaxant, anticonvulsant, and amnesic effects when administered.[2]

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

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.[4][5] Peak benefits achieved for generalized anxiety disorder (GAD) may take up to a week.[6]

It is worth noting that 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.[7] 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.[8]

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.[9] 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.[10]

Alprazolam causes a marked suppression of the hypothalamicpituitary-adrenal axis. Administration of alprazolam has been demonstrated to elicit an increase in striatal dopamine concentrations.[11]

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed 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 and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include 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:

Preparation methods

  • Volumetric liquid dosing - If one's benzodiazepines are in powder form, they are unlikely to weigh out accurately without the most expensive of scales due to their extreme potency. To avoid this, one can dissolve the benzodiazepine volumetrically into a nonpolar solution such as propylene glycol and dose it accurately based upon the methodological instructions linked within this tutorial.

Toxicity and harm potential

Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.[17]

Alprazolam has a low toxicity relative to dose.[18] 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 (over 195 mg/kg; 975 times the maximum recommended daily human dose of 10 mg/day).

Tolerance and addiction potential

Alprazolam is extremely physically and psychologically addictive.

Tolerance will develop to the sedative-hypnotic effects within a couple of days of continuous use.[19] 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.

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.[20] 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]

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, cross-potentiating each other.[citation needed]

For example, 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.[21] This can result in dangerously disinhibited, total blackout states along with potential lethal respiratory depression.[citation needed]

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;[22] however, care is primarily supportive in nature.

Dangerous interactions

Although many psychoactive substances are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

  • 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.

Legality

  • International: Alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.[23]
  • United States: Alprazolam is a prescription medication assigned to Schedule IV of the Controlled Substances Act by the DEA.[24]
  • United Kingdom: The drug 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.[25]
  • Ireland: Alprazolam is a Schedule 4 medicine.[26]
  • Sweden: Alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).[27]
  • The Netherlands: In the Netherlands, alprazolam is a List 2 substance of the Opium Law and is available for prescription.
  • 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]
  • Germany: Alprazolam is in Anlage III (BtmG) prescription drug only.

See also

External links

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. FDA approved labeling for Xanax revision 08/23/2011 | http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018276s045lbl.pdf
  4. Pharmacokinetics and Pharmacodynamics of Alprazolam after Oral and IV Administration (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6152055
  5. 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
  6. 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
  7. A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812
  8. 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
  9. Benzodiazepine interactions with GABA receptors (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6147796
  10. 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
  11. 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
  12. http://www.ncbi.nlm.nih.gov/pubmed/18922233 | Saïas T, Gallarda T | Paradoxical aggressive reactions to benzodiazepine use: a review
  13. Paton C | Benzodiazepines and disinhibition: a review | Psychiatr Bull R Coll Psychiatr | http://pb.rcpsych.org/cgi/reprint/26/12/460.pdf
  14. Bond AJ | Drug-induced behavioural disinhibition: incidence, mechanisms and therapeutic implications | CNS Drugs
  15. Drummer OH | Benzodiazepines—effects on human performance and behavior | Forensic Sci Rev
  16. Goyal, Sarita. "Drugs and Dreams." Indian Journal of Clinical Practice (n.d.): n. pag. Web. | http://medind.nic.in/iaa/t13/i3/iaat13i3p624.pdf
  17. Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644
  18. Benzodiazepine metabolism: an analytical perspective (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614
  19. Principles and Practice of Psychopharmacotherapy | http://books.google.com/books?id=_ePK9wwcQUMC&pg=PA535
  20. A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812
  21. Twyman, R. E., Rogers, C. J., & Macdonald, R. L. (1989). Differential regulation of γ‐aminobutyric acid receptor channels by diazepam and phenobarbital. Annals of Neurology, 25(3), 213-220. https://doi.org/10.1002/ana.410250302
  22. 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
  23. List of Psychotropic Substances under International Control | http://www.incb.org/documents/Psychotropics/green_lists/Green_list_ENG_2014_85222_GHB.pdf
  24. DEA, Drug Scheduling | http://www.deadiversion.usdoj.gov/schedules/index.html
  25. Misuse of Drugs Act 1971 (c. 38) | http://www.legislation.gov.uk/ukpga/1971/38/schedules
  26. Misuse Of Drugs (Amendment) Regulations | http://www.irishstatutebook.ie/1993/en/si/0342.html
  27. "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
  28. Alprazolam to be rescheduled from next year | http://www.australiandoctor.com.au/news/latest-news/alprazolam-to-be-rescheduled-from-next-year