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Alprazolam

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Alprazolam (Xanax)
File:Xanax.png
The skeletal formula of Alprazolam.
Dosage (Oral)
Threshold 0.25 mg
Light 0.25 - 0.75 mg
Common 1 - 3 mg
Strong 3 - 6 mg
Heavy 7 mg+
Duration
Total duration 2 - 6 hours
Onset / Initial effects 15 minutes
Coming up 20 - 90 minutes
Peak 1 - 2 hours
Coming down 2 - 6 hours
After effects 2 - 4 hours

Alprazolam (trade name Xanax) is a short-acting psychoactive drug of the benzodiazepine class which produces anxiolytic, sedative, hypnotic, muscle relaxant, anticonvulsant, and amnestic effects. [1] Alprazolam, like other benzodiazepines, binds to specific sites on the GABAA gamma-amino-butyric acid receptor. Alprazolam is commonly used and FDA approved for the medical treatment of panic disorder, generalized anxiety disorder (GAD), or social anxiety disorder (SAD). [2]

Alprazolam has a fast onset of action and symptomatic relief. Ninety percent of peak effects are achieved within the first hour of using either in preparation for panic disorder and full peak effects are achieved in 1.5 and 1.6 hours respectively. [3] [4] Peak benefits achieved for generalized anxiety disorder (GAD) may take up to a week.[5]

Chemistry

Alprazolam is classed as a high-potency benzodiazepine and is a triazolobenzodiazepine, namely a benzodiazepine with a triazole ring attached to its structure. Alprazolam is a chemical analog of triazolam that differs by the absence of a chlorine atom in the o-position of the 6-phenyl ring. [6] [7]

Pharmacology

Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site on the GABAA receptor and modulating the function of the GABA receptor, the most prolific inhibitory receptor within the brain. The GABA chemical and receptor system mediates inhibitory (or calming effects) of alprazolam on the nervous system.

Alprazolam causes a marked suppression of the hypothalamicpituitary-adrenal axis. Administration of alprazolam has been demonstrated to elicit an increase in striatal dopamine concentrations.[8]

Subjective effects

Physical Effects

The physical effects of Alprazolam can be broken down into 3 components all of which progressively intensify proportional to dosage. These are described below and generally include:

  • Sedation - In terms of energy level alterations, Alprazolam is extremely sedating and often results in an overwhelmingly lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness.
  • Dizzness
  • Loss of motor control

Cognitive Effects

The cognitive effects of Alprazolam can be broken down into 6 components all of which progressively intensify proportional to dosage. The general head space of Alprazolam is described by many as one of intense sedation and decreased inhibition. It contains a large number of typical depressant cognitive effects.

The most prominent of these cognitive effects generally include:

Toxicity and Harm Potential

Lethal Dosage

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).

A xanax overdose can be lethal when mixed with other depressants including alcohol or opiates.

Tolerance and Addiction Potential

Tolerance will develop to the sedative-hypnotic effects within a couple of days.[9] Withdrawal symptoms or rebound symptoms may occur after ceasing treatment abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction.[10] [11]

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 seizure following discontinuation of benzodiazepines. Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.

  • International: Alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.[12]
  • United States: Alprazolam is a prescription medication assigned to Schedule IV of the Controlled Substances Act by the DEA. [13]
  • 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.[14]
  • Ireland: Alprazolam is a Schedule 4 medicine.[15]
  • Sweden: Alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).[16]
  • 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.[17]

See Also

References

  1. Benzodiazepine Metabolism: An Analytical Perspective" | http://www.ncbi.nlm.nih.gov/pubmed/18855614
  2. FDA approved labeling for Xanax revision 08/23/2011 | http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018276s045lbl.pdf
  3. Pharmacokinetics and Pharmacodynamics of Alprazolam after Oral and IV Administration | http://www.ncbi.nlm.nih.gov/pubmed/6152055
  4. The Speed of Onset of Action of Alprazolam-XR Compared to Alprazolam-CT in Panic Disorder | http://www.ncbi.nlm.nih.gov/pubmed/17514187
  5. 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
  6. Spontaneous Withdrawal from the Triazolobenzodiazepine Alprazolam Increases Cortical Corticotropin-Releasing Factor mRNA Expression | http://www.jneurosci.org/content/24/42/9303.long
  7. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound | http://www.ncbi.nlm.nih.gov/pubmed/15078112
  8. Role of dopaminergic and serotonergic systems on behavioral stimulatory effects of low-dose alprazolam and lorazepam | http://www.ncbi.nlm.nih.gov/pubmed/11226811
  9. Principles and Practice of Psychopharmacotherapy | http://books.google.com/books?id=_ePK9wwcQUMC&pg=PA535
  10. 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
  11. The American Psychiatric Publishing Textbook of Substance Abuse Treatment | http://books.google.com/books?id=6wdJgejlQzYC&pg=PA222&hl=en#v=onepage&q&f=false
  12. List of Psychotropic Substances under International Control | http://www.incb.org/documents/Psychotropics/green_lists/Green_list_ENG_2014_85222_GHB.pdf
  13. DEA, Drug Scheduling | http://www.deadiversion.usdoj.gov/schedules/index.html
  14. Misuse of Drugs Act 1971 (c. 38) | http://www.legislation.gov.uk/ukpga/1971/38/schedules
  15. Misuse Of Drugs (Amendment) Regulations | http://www.irishstatutebook.ie/1993/en/si/0342.html
  16. "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
  17. Alprazolam to be rescheduled from next year | http://www.australiandoctor.com.au/news/latest-news/alprazolam-to-be-rescheduled-from-next-year