|Summary sheet: Alprazolam|
|Common names||Xanax, Alprazolam|
|Routes of Administration|
Like other benzodiazepines, alprazolam binds to specific sites on the GABAA receptor. It is commonly used for the medical treatment of panic disorder, generalized anxiety disorder (GAD), or social anxiety disorder (SAD).
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. Peak benefits achieved for generalized anxiety disorder (GAD) may take up to a week.
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. 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.
- 1 Chemistry
- 2 Pharmacology
- 3 Subjective effects
- 4 Toxicity and harm potential
- 5 Legality
- 6 See also
- 7 External links
- 8 References
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".
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. 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 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.
- Sedation - 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 have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out. This sleep deprivation increases proportionally to dosage and eventually becomes powerful enough to force a person into a deep state of unconsciousness.
- Appetite enhancement - This effect is not particularly prominent, but is reported to occur in some people. It can have a synergistic effect when combined with cannabis.
- Muscle relaxation - In comparison to diazepam (Valium), alprazolam presents lesser amounts of muscle relaxation.
- Motor control loss
- Respiratory depression
- Seizure suppression
- 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.
- 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%).
The cognitive effects of alprazolam can be broken down into several components which progressively intensify proportional to dosage. The general head space of alprazolam is described by many as one of intense sedation, relaxation, anxiety suppression and decreased inhibition. It contains a large number of typical depressant cognitive effects.
The most prominent of these cognitive effects generally include:
- Anxiety suppression
- Thought deceleration
- Analysis suppression
- 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.
- Compulsive redosing
- Emotion suppression - Although this compound primarily suppresses anxiety, it also dulls other emotions in a manner which is distinct but less intensive than that of antipsychotics.
- 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.
- Memory suppression - Alprazolam primarily suppresses short-term memory, resulting in forgetfulness, and/or disorganized behaviors.
- Confusion - At heavy doses, alprazolam can cause confusion. This effect is a result of the drug suppressing basic cognitive functions at heavy doses, such as comprehension, memory, and reasoning skills.
- 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 on this compound, especially at higher doses.
- Language suppression - Alprazolam is known to cause slurred speech and difficulty communicating words in a clear fashion.
- Dream potentiation
- 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.
- Dream potentiation or Dream suppression
- 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.
- Thought deceleration
- Thought disorganization
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
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. 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.
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. Substances which lower the seizure threshold such as tramadol should be avoided during withdrawal. Abrupt discontinuation also causes rebound stimulation which presents as anxiety, insomnia and restlessness.
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.
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.
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. This can result in dangerously disinhibited, total blackout states along with potential lethal respiratory depression.
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; however, care is primarily supportive in nature.
Although many psychoactive substances are safe to use on their own, they can become dangerous or even life-threatening when taken with other substances. The list below contains some potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses but still increase the possibility of injury of death. Independent research should always be conducted to ensure that a combination of two or more substances is safe before consumption.
- Depressants (1,4-Butanediol, 2M2B, alcohol, benzodiazepines, barbiturates, GHB/GBL, methaqualone, opioids) - This combination potentiates the muscle relaxation, amnesia, sedation, and respiratory depression caused by one another. At higher doses, it can lead to a sudden, unexpected loss of consciousness along with a dangerous amount of depressed respiration. There is also an increased risk of suffocating on one's vomit while unconscious. If nausea or vomiting occurs before a loss of consciousness, users should attempt to fall asleep in the recovery position or have a friend move them into it.
- 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.
- 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.
- International: Alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.
- 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).
- United States: Alprazolam is a prescription medication assigned to Schedule IV of the Controlled Substances Act by the DEA.
- 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.
- Ireland: Alprazolam is a Schedule 4 medicine.
- Sweden: Alprazolam is a prescription drug in List IV (Schedule 4) under the Narcotics Drugs Act (1968).
- 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.
- Germany: Alprazolam is in Anlage III (BtmG) prescription drug only.
- Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
- Benzodiazepine Metabolism: An Analytical Perspective" (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614
- FDA approved labeling for Xanax revision 08/23/2011 | http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/018276s045lbl.pdf
- Pharmacokinetics and Pharmacodynamics of Alprazolam after Oral and IV Administration (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6152055
- 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
- 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
- A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812
- 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
- Benzodiazepine interactions with GABA receptors (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6147796
- 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
- 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
- http://www.ncbi.nlm.nih.gov/pubmed/18922233 | Saïas T, Gallarda T | Paradoxical aggressive reactions to benzodiazepine use: a review
- Paton C | Benzodiazepines and disinhibition: a review | Psychiatr Bull R Coll Psychiatr | http://pb.rcpsych.org/cgi/reprint/26/12/460.pdf
- Bond AJ | Drug-induced behavioural disinhibition: incidence, mechanisms and therapeutic implications | CNS Drugs
- Drummer OH | Benzodiazepines—effects on human performance and behavior | Forensic Sci Rev
- Goyal, Sarita. "Drugs and Dreams." Indian Journal of Clinical Practice (n.d.): n. pag. Web. | http://medind.nic.in/iaa/t13/i3/iaat13i3p624.pdf
- Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644
- Benzodiazepine metabolism: an analytical perspective (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614
- Principles and Practice of Psychopharmacotherapy | http://books.google.com/books?id=_ePK9wwcQUMC&pg=PA535
- A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812
- 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
- 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
- List of Psychotropic Substances under International Control | http://www.incb.org/documents/Psychotropics/green_lists/Green_list_ENG_2014_85222_GHB.pdf
- DEA, Drug Scheduling | http://www.deadiversion.usdoj.gov/schedules/index.html
- Misuse of Drugs Act 1971 (c. 38) | http://www.legislation.gov.uk/ukpga/1971/38/schedules
- Misuse Of Drugs (Amendment) Regulations | http://www.irishstatutebook.ie/1993/en/si/0342.html
- "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
- Alprazolam to be rescheduled from next year | http://www.australiandoctor.com.au/news/latest-news/alprazolam-to-be-rescheduled-from-next-year