Alprazolam

There is a high incidence of death due to respiratory depression when benzodiazepines are combined with depressants such as opiates, alcohol or other GABAergic substances.

Alprazolam
The skeletal formula of Alprazolam.
Chemical Nomenclature
Common names	Alprazolam, Xanax
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
Oral Dosage WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. Threshold 0.25 - 0.5 mg Light 0.5 - 1 mg Common 1 - 3 mg Strong 3 - 6 mg Heavy 7 mg+ Duration Total 2 - 6 hours Onset 15 - 90 minutes Peak 1 - 2 hours Offset 2 - 6 hours Afterglow 2 - 4 hours

Summary sheet: Alprazolam

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. 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).

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.

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 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.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects will rarely (if ever) occur all at once, but heavier dosages will increase the chances and are more likely to induce a full range of effects.

Physical effects

The physical effects of alprazolam can be broken down into several components which progressively intensify proportional to dosage.

These are listed below and generally include:

• Sedation - In terms of energy level alterations, this drug has the potential to be 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.
• Dizziness
• Muscle relaxation
• Motor control loss
• Respiratory depression
• Seizure suppression

Cognitive effects

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:

• Amnesia
• Anxiety suppression
• Thought deceleration
• Disinhibition
• Information processing suppression
• Compulsive redosing
• 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.

Paradoxical effects

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%).

These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.

Toxicity and harm potential

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

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).

As with all GABAergic drugs, overdose can be lethal when mixed with other depressants including alcohol or opioids.

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. 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.

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.

Alprazolam presents cross-tolerance with all benzodiazepines, meaning that after its consumption all benzodiazepines will have a reduced effect.

Dangerous interactions

Although many drugs 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.

• Depressants (1,4-Butanediol, 2-methyl-2-butanol, alcohol, barbiturates, GHB/GBL, methaqualone, opioids) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances also potentiate the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
• Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
• Stimulants - It is dangerous to combine benzodiazepines with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of benzodiazepines, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of benzodiazepines will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only dosing a certain amount of benzodiazepines per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.

Legal issues

• International: Alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.
• 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.

Preparation methods

Preparation methods for this compound within our preparation index include:

• Volumetric liquid dosing

See also

• Responsible use
• Psychoactive substance index
• Entactogens
• Alcohol
• Benzodiazepines
• Depressants