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Difference between revisions of "Alprazolam"

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Alprazolam (often seen as under the trade name Xanax) is a sedative drug prescribed for the treatment of anxiety/stress/depression, panic attacks, and sleep disorders <ref name="1a">'''Alprazolam''', 2017, http://www.release.org.uk/drugs/alprazolam</ref>.
 
Alprazolam (often seen as under the trade name Xanax) is a sedative drug prescribed for the treatment of anxiety/stress/depression, panic attacks, and sleep disorders <ref name="1a">'''Alprazolam''', 2017, http://www.release.org.uk/drugs/alprazolam</ref>.
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== Medical usage ==
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Short-term use in anxiety <ref name="23a">'''Alprazolam''', 2017, https://www.evidence.nhs.uk/formulary/bnf/current/4-central-nervous-system/41-hypnotics-and-anxiolytics/412-anxiolytics/benzodiazepines/alprazolam</ref>.
  
 
== What does it look like? ==
 
== What does it look like? ==
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* reduced blood pressure,
 
* reduced blood pressure,
 
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== Dosage ==
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=== Therapeutic ===
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* 250 - 500 micrograms 3 times daily (elderly or debilitated 250 micrograms 2 - 3 times daily), increased if necessary to a total of 3 mg daily; child not recommended (cite:1010).
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=== Abuse ===
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==== Oral ====
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* Threshold 0.10 - 0.25 mg,
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* Light 0.25 - 0.5 mg,
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* Common 0.5 - 1.5 mg,
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* Strong 1.5 - 2 mg,
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== How long do its effects last? ==
 
== How long do its effects last? ==
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* acuity suppression <ref name="4a"/>.
 
* acuity suppression <ref name="4a"/>.
  
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Latest revision as of 09:43, 25 April 2017

Also known as

Xanax (brand name), prazolam, ksalol, xannies, bars, z-bars, zanbars, xanbars, handlebars, planks, bricks

Classification

Depressant

Overview

Alprazolam (often seen as under the trade name Xanax) is a sedative drug prescribed for the treatment of anxiety/stress/depression, panic attacks, and sleep disorders [1].

Medical usage

Short-term use in anxiety [2].

What does it look like?

Small pills, usually oval though can be other shapes. They come at different strengths (0.25mg, 0.5mg and 1mg being the most common) and in a range of different colours (white, orange and pink most often) and the colour is usually linked to the strength of the pill. They are also found (rarely) in capsule form [1].

Source

Alprazolam is only legally available through prescription. Many abusers maintain their drug supply by getting prescriptions from several doctors, forging prescriptions, or buying them illicitly [3].

Why take it?

Sought after effects

  • relaxation,
  • sleepiness,
  • occasional mild euphoria (happiness) [1],
  • feelings of peace and tranquility,
  • relaxation of the body and mind,
  • improved sleep [4].

Undesired effects

  • drowsiness,
  • dizziness/loss of coordination,
  • headaches,
  • sometimes mild amnesia [1],
  • problems with speech and coordination,
  • feeling dizzy and disoriented,
  • poor memory and concentration,
  • reduced blood pressure,
  • reduced respiration rate [4].

Dosage

Therapeutic

  • 250 - 500 micrograms 3 times daily (elderly or debilitated 250 micrograms 2 - 3 times daily), increased if necessary to a total of 3 mg daily; child not recommended (cite:1010).

Abuse

Oral

  • 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 + [5].

How long do its effects last?

Onset of effects

Peak

  • 1 - 2 hours [5].

Offset

  • 2 - 6 hours [5].

Duration of effects

After*effects

  • 6 - 24 hours [5].
  • all ROA's - 6 - 24 hours [7].

Pharmacology

Following oral administration, alprazolam is quickly absorbed and metabolised by the body. Peak concentrations in plasma (proportionate to the dose) occur approximately 1 to 2 hours after ingestion. The metabolites 4-hydroxyalprazolam and a-hydroxyalprazolam are chiefly responsible for alprazolam's metabolisation.

The precise mechanism of action in alprazolam is not currently known; merely that it enhances the body's GABA, the CNS's primary inhibitory neurotransmitter. Alprazolam is believed to act by strengthening (rather than adding to) the body's existing GABA, which quietens the neurons in the brain, thereby calming the brain and subsequently the mind [1].

Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter GABA by acting on its receptors [8]. 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 [9].

Alprazolam causes a marked suppression of the hypothalamicpituitary-adrenal axis. Administration of alprazolam has been demonstrated to elicit an increase in striatal dopamine concentrations [10], [5].

Pharmacodynamics

Alprazolam, a benzodiazepine, is used to treat panic disorder and anxiety disorder. Unlike chlordiazepoxide, clorazepate, and prazepam, alprazolam has a shorter half-life and metabolites with minimal activity. Like other triazolo benzodiazepines such as triazolam, alprazolam may have significant drug interactions involving the hepatic cytochrome P-450 3A4 isoenzyme. Clinically, all benzodiazepines cause a dose-related central nervous system depressant activity varying from mild impairment of task performance to hypnosis. Unlike other benzodiazepines, alprazolam may also have some antidepressant activity, although clinical evidence of this is lacking [11].

Absorption

Alprazolam is absorbed fairly rapidly, with peak plasma levels achieved around the one-two hour mark [6].

Bioavailability

Oral 80%--90% [7].

Metabolism

It is primarily metabilised via CYP3A4. Alprazolam is a chemical analogue of triazolam. It is a triazolobenzodiazepine. It binds to the GABA(a) receptor and modulates the function of the GABA receptor [6]. Hepatic. Hydroxylated in the liver to α-hydroxyalprazolam, which is also active. This and other metabolites are later excreted in urine as glucuronides [11].

Half-life

6.3 - 26.9 hours [11].

Elimination

Alprazolam and its metabolites are largely excreted in urine [1].

Lethal dosage

The LD50 of Alprazolam in rats is 331-2171mg/kg [6]. Oral, mouse: LD50 is 1020 mg/kg [11].

Mechanism of action

Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell [11].

Signs of usage

  • increased conflict with friends, family, and coworkers,
  • decreased performance at work or school,
  • financial changes with more money being spent on the substance,
  • contacting multiple doctors for prescriptions ('doctor shopping' for xanax) [4],
  • slurred speech,
  • shallow breathing,
  • sluggishness,
  • fatigue,
  • disorientation,
  • lack of coordination,
  • dilated pupils,
  • impaired memory, judgement and coordination,
  • irritability,
  • paranoia,
  • thoughts of suicide [12].

Effects

Physical effects

  • muscle relaxation,
  • physical euphoria,
  • perception of increased weight,
  • motor control loss,
  • respiratory depression,
  • sedation,
  • seizure suppression,
  • decreased heart rate,
  • dizziness [5].

Cognitive effects

  • compulsive redosing,
  • delusions,
  • dream potentiation,
  • amnesia,
  • analysis suppression,
  • anxiety suppression,
  • confusion,
  • disinhibition,
  • emotion suppression,
  • information processing suppression,
  • language suppression,
  • memory suppression,
  • motivation suppression,
  • thought deceleration [5].

Visual effects

  • acuity suppression [5].

Over-sedation

  • impaired thinking and judgement,
  • memory problems,
  • confusion,
  • disorientation,
  • slurred speech,
  • weakness of the muscles,
  • coordination problems [13].

Positive

  • euphoria,
  • relaxation,
  • anti-anxiety effects [6].

Neutral

  • drowsiness,
  • appetite fluctuation [6].

Negative

  • memory loss,
  • blackout potential,
  • motor skill impairment,
  • dizziness,
  • depression,
  • irritability, aggression, rage,
  • personality changes,
  • emotional and social dissociation or de-realization (long term use) [6].

Dependency

Physical

  • increased depression,
  • thoughts of suicide or of harming oneself,
  • dizziness and fainting,
  • heavy sweating,
  • decreased urination,
  • constipation,
  • diarrhoea,
  • nausea and vomiting,
  • headache,
  • excruciating joint pain,
  • muscle weakness,
  • blurred vision,
  • impaired coordination and balance,
  • rapid heartbeat,
  • muscular twitching,
  • seizures,
  • stuffy nose,
  • oedema,
  • heart palpitations,
  • jaundice [14].

Psychological

  • difficulty concentrating,
  • thoughts of suicide,
  • hallucinations,
  • disorientation,
  • confusion,
  • memory problems [14].
        • Abuse

Many of the drug's effects are possible even when taking the medication as prescribed. Abuse of the substance will heighten and intensify these effects. Alprazolam abuse is marked by -

  • taking the substance more often or in higher doses than prescribed,
  • taking the substance without a prescription,
  • taking the substance for non-medical reasons [4].
  • confusion,
  • light-headedness,
  • headache,
  • tiredness,
  • dizziness,
  • irritability,
  • talkativeness,
  • difficulty concentration,
  • dry mouth,
  • increased salivation,
  • changes in sex drive or ability,
  • nausea,
  • constipation,
  • changes in appetite,
  • weight changes,
  • difficulty urinating,
  • joint pain [15].

Side-effects

Columbia University states that "respiratory problems, such as destruction of the nasal and sinus cavities and lung tissue" can result from inhaling prescription stimulants [16]. Unfortunately, the same issue can occur when someone snorts Xanax and other prescription sedatives. The continuous introduction of foreign objects into the nasal cavity can have effects on this part of the body no matter what drug the individual is snorting [16].

Other health effects include -

  • mood disturbances - Some individuals develop signs of mood disorders such as depression or bipolar disorder after abusing drugs like Xanax in the long term.
  • erratic behaviour - High doses of benzodiazepines can cause hostile behavior or cause users to act irrationally. This is very likely to occur among individuals who snort Xanax because they will be more likely to abuse continuous doses of the drug.
  • gastrointestinal problems - nausea, vomiting, and constipation are all common with Xanax abuse.
  • vision problems - Some individuals experience blurry or altered vision when abusing Xanax [16].

Individuals who snort Xanax are extremely likely to become addicted to the drug while also experiencing extreme health issues and dangerous side effects. No one should snort Xanax as the drug is meant to be taken orally and by prescription only [16].

Overdose

  • drowsiness,
  • shallow respiration,
  • clammy skin,
  • dilated pupils,
  • weak and rapid pulse,
  • confusion,
  • coma,
  • possible death [17].

Risks

  • dependence,
  • aggression or violence - particularly if the dose is high, the person is quite impulsive, has a history of aggression, or is also under the influence of alcohol,
  • skin and vein problems (if injected),
  • withdrawals - which can lead to seizures and death if not managed correctly,
  • blackouts',
  • overdose - especially if the person also drinks alcohol, takes other depressant drugs (e.g. heroin) or takes opioid painkillers (e.g. OxyContin or morphine),
  • sedation - including impairing driving the day following use [18].

Addiction

Can you get addicted

Yes, alprazolam is extremely physically and psychologically addictive [5].

Tolerance

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 [5].

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 [5].

  • 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 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 [5].

Dangerous

  • alcohol - Ethanol ingestion may potentiate the CNS effects of many benzodiazepines. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Blacking out and memory loss is almost certain.
  • GBL / GHB - The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position.
  • opioids - Central nervous system and/or respiratory-depressant effects may be additively or synergistically present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position Blackouts/memory loss likely
  • tramadol - Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present. Vomit aspiration a risk when passed out, lay down in recovery position if ingested [7].

Unsafe

  • PCP - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely [7].

Withdrawal

Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction [20], [21].

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 hypertension, seizures, and death [22]. Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal [5].

  • intense anxiety,
  • inability to sleep,
  • irritability and depression,
  • shakiness,
  • seizures [4],
  • depersonalisation,
  • hypersensitivity,
  • physical tremors,
  • psychosis [15],
  • blurred vision,
  • headache,
  • weight loss,
  • pain in the hands and feet,
  • nausea and vomiting [13],
  • teeth pain,
  • loss of appetite,
  • paranoia,
  • cramps,
  • panic,
  • suicidal ideation [23].

It is extremely unlikely that you will experience all of these withdrawal symptoms. And the variety and intensity of your alprazolam withdrawal symptoms can be influenced by various factors, such as -

  • high stress levels,
  • family history of drug abuse,
  • medical complications,
  • the social environment you live in,
  • how long you've been taking alprazolam for,
  • the dosage,
  • if you've been taking alprazolam alongside other drugs,
  • consumption of alcohol,
  • method of ingestion [23].

Timeline

  • 6 - 12 hour after your last dose - This is when the symptoms start to make themselves noticed.
  • 2 - 4 days after your last dose - During this period, the withdrawal symptoms reach their peak and can become extremely unbearable, which can result in you relapsing without any medical assistance by your side.
  • 7 - 14 days after your last dose - During this phase, some of the withdrawal symptoms start to decrease in severity.
  • 15+ days after your last dose - By this time, most of the symptoms you've been dealing with will start to go away [23].

I should add that just because the 15+ days phase might seem like it's the end of the addiction doesn't mean it really is. In fact, if you are unlucky enough, you might develop "Protracted Withdrawal Symptoms". Essentially, they are similar to alprazolam withdrawal symptoms, but they occur randomly and can last up to 2 years! [23]

Drug testing

Determining exactly how long alprazolam is detectable in the body depends on many variables, including which kind drug test is being used. Xanax - which is a benzodiazepine (alprazolam) - can be detected for a shorter time with some tests, but can be "visible" for up to three months in other tests.

The timetable for detecting Xanax in the system is also dependent upon each individual's metabolism, body mass, age, hydration level, physical activity, health conditions and other factors, making it almost impossible to determine an exact time Xanax will show up on a drug test [17].

  • Age - Xanax has been found to leave the system of younger users faster than elderly people. Most individuals 65 years and older will have their internal organs (for example the liver) functioning at a slower pace making it more difficult for them to excrete the substance.
  • Metabolism speed - Although it is unclear how one's metabolic rate influences their body's ability to excrete Xanax, many findings have indicated that it does have a slight effect on Xanax clearance. A higher BMR is believe to causes a faster clearance while a lower BMR may result in delayed clearance.
  • Height and Weight - How tall or fat a person is can affect how fast Xanax is excreted from their body. Heavier/taller people are believed to be able to clear the drug quicker than their lightweight/shorter counterparts. This is because the heavyweight/taller person would have usually taken a smaller dose in proportion to their body.
  • Amount of ingested - Users on higher dosages may require a longer period for the drug to be fully excreted from their body. Most doctors will recommend between 0.25 mg and 4 mg to treat patients with depression or anxiety. A lot of the times people will end up exceeding 4 mg, making it more difficult for the drug to be excreted.
  • Length of use - How long an individual uses Xanax can affect how quickly it is excreted from their body. Those who use the drug for a longer period generally require a longer period to remove the drug from their body.
  • Liver and kidneys health - Xanax tend to linger longer in the bodies of individuals with a pre existing liver or kidney illness. This is because both organs are important for excreting toxins from the body [14].

The following is an estimated range of times, or detection windows, during which Xanax can be detected by various testing methods -

How long does xanax stay in urine?

Xanax can be detected in a urine test for up to 1 - 6 weeks [17].

How long does xanax remain in the blood?

Blood tests for Xanax can detect the drugs for up to 6 - 48 hours [17].

How long can xanax be detected in saliva?

A saliva test can detect Xanax for 1 - 10 days [17].

How long does xanax remain in hair?

Xanax, like like many other drugs, can be detected with a hair follicle drug test for up to 90 days [17].

Harm reduction

  • alcohol can interact negatively with benzodiazepines, so it's not a good idea to drink while you're taking them,
  • benzodiazepines can also interact with one another, so it's not a good idea to take Xanax/alprazolam if you are already taking something similar. If in doubt, check with a doctor,
  • if you've been prescribed Xanax/alprazolam and you notice a tolerance starting to develop (you need to keep taking more to get the same effect) speak to your doctor * don't just start increasing your dose yourself,
  • don't suddenly stop taking them, or you may start to experience symptoms of withdrawal * these can range from a return of your original symptoms (possibly even worse than before) to totally new symptoms,
  • if you have become addicted to Xanax, the symptoms of abruptly stopping are likely to be even worse * it's important to get proper medical advice on how to reduce your intake slowly,
  • it's also possible to become psychologically dependent on the drug (feeling like you need it all the time) - if you think this is happening, see your doctor as soon as possible, but don't suddenly stop taking it [1].

When on high doses of benzodiazepines, users are likely to black out and potentially hurt themselves through a variety of adventures [6].

History

Alprazolam was one of a raft of drugs created by Dr Jackson B. Hester Jr. for the Upjohn Company (now part of Pfizer), who applied for the patent in 1969. It was granted in 1976, and alprazolam was first marketed in 1981. The patent expired in 1993, and whilst Pfizer still hold the trade name 'Xanax', a number of generic variants have since come on to the market. Some illegal producers of alprazolam use Xanax logos and typography in an attempt to make their product look genuine.

The recreational use of the drug has been recorded since the earliest days of its release. Its efficacy as a sedative means it has been widely prescribed, and the quick build-up of tolerance has meant many who started taking it under doctors' guidance have been driven to obtaining it illegally in order to sustain their increased needs. As such, and as with other benzodiazepines, there is a small but specialised market in its illicit supply [1].

Alprazolam was first released by Upjohn, under the brand name Xanax. The patent was filed in October 1969, granted in October of 1976, and expired in September of 1993. It was first released in 1981, for the treatment of panic disorders [6].


References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Alprazolam, 2017, http://www.release.org.uk/drugs/alprazolam
  2. Alprazolam, 2017, https://www.evidence.nhs.uk/formulary/bnf/current/4-central-nervous-system/41-hypnotics-and-anxiolytics/412-anxiolytics/benzodiazepines/alprazolam
  3. Benzodiazepines, 2016, http://www.dea.gov/druginfo/drug_data_sheets/Benzodiazepines.pdf
  4. 4.0 4.1 4.2 4.3 4.4 Patterson, E., Alprazolam Abuse, 2017, http://drugabuse.com/library/alprazolam-abuse/
  5. 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 Alprazolam, 2017, https://psychonautwiki.org/wiki/Alprazolam
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 Alprazolam, 2017, https://wiki.tripsit.me/wiki/Alprazolam
  7. 7.0 7.1 7.2 7.3 7.4 7.5 Alprazolam, 2016, http://drugs.tripsit.me/alprazolam
  8. Haefely, W., Benzodiazepine interactions with GABA receptors, Neuroscience letters, 1984, 47, 3, 201-206, https://www.ncbi.nlm.nih.gov/pubmed/6147796
  9. McLean, M. J. and Macdonald R. L., Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture, Journal of Pharmacology and Experimental Therapeutics, 1988, 244, 2, 789-795, https://www.ncbi.nlm.nih.gov/pubmed/2450203
  10. Bentué-Ferrer, D. and Reymann, J. M. and Tribut, O. and Allain, H. and Vasar, E. and Bourin, M., Role of dopaminergic and serotonergic systems on behavioral stimulatory effects of low-dose alprazolam and lorazepam, European Neuropsychopharmacology, 2001, 11, 1, 41-50, https://www.ncbi.nlm.nih.gov/pubmed/11226811
  11. 11.0 11.1 11.2 11.3 11.4 Alprazolam, 2017, https://www.drugbank.ca/drugs/DB00404
  12. Xanax, 2017, http://drugfree.org/drug/xanax/
  13. 13.0 13.1 Snorting Xanax: Dangers, Complications & Why You Shouldn't Snort Xanax, 2017, https://www.addictions.com/ativan-addiction/snorting-xanax-dangers-complications-why-you-shouldnt-snort-xanax/
  14. 14.0 14.1 14.2 Xanax side effects, symptoms & treatment, 2017, https://www.blvdcenters.org/xanax-rehab-centers/xanax-side-effects-symptoms-treatment
  15. 15.0 15.1 Signs and Symptoms of Xanax Abuse, 2017, https://www.addictions.com/xanax-an-overview-of-abuse-addiction-signs-symptoms-treatment/
  16. 16.0 16.1 16.2 16.3 Snorting Adderall and Ritalin, 2014, http://goaskalice.columbia.edu/answered-questions/snorting-adderall-and-ritalin
  17. 17.0 17.1 17.2 17.3 17.4 17.5 How Long Does Xanax Stay in Your System?, 2016, https://www.verywell.com/how-long-does-xanax-stay-in-your-system-80348
  18. Nielsen, S.,Benzodiazepines, 2016, https://ndarc.med.unsw.edu.au/sites/default/files/ndarc/resources/NDA073_Fact_Sheet_Benzodiazepines.pdf
  19. Janicak, P. G. and Marder, S. R. and Pavuluri, M. N., Principles and Practice of Psychopharmacotherapy, 2010, 5th edition, Lippincott Williams & Wilkins, ISBN 9781605475653, 700, http://books.google.com/books?id=_ePK9wwcQUMC&pg=PA535
  20. Verster, J. C. and Volkerts, E. R., Clinical Pharmacology, Clinical Efficacy, and Behavioral Toxicity of Alprazolam: A Review of the Literature, CNS Drug Reviews, 2004, 10, 1, 45-76, https://doi.org/10.1111/j.1527-3458.2004.tb00003.x, http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2004.tb00003.x/abstract
  21. Galanter, M. and Kleber, H. D., The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 2008, American Psychiatric Pub., ISBN 9781585622764, https://books.google.co.uk/books?id=6wdJgejlQzYC
  22. Lann, M. A. and Molina, D. K., A fatal case of benzodiazepine withdrawal, American Journal of Forensic Medicine and Pathology, 2009, 30, 2, 177-179, https://doi.org/10.1097/PAF.0b013e3181875aa0, https://www.ncbi.nlm.nih.gov/pubmed/19465812
  23. 23.0 23.1 23.2 23.3 Xanax withdrawal - what you need to know, 2017, https://www.blvdcenters.org/xanax-rehab-centers/xanax-withdrawal