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== Other Names ==
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Diazepam (Also known as Diastat; Valium; Zetran) is a [[Benzodiazepines|benzodiazepine]] that is commonly used to treat a large range of conditions from anxiety to Meniere’s Disease. It possesses anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnesic properties. It is also one of the most commonly used drugs to taper off of other [[Benzodiazepines|benzodiazepines]]/[[Alcohol]] withdrawal.
  
7-chlor-1,3-dihydro-1-methyl-5-phenyl-2H-1,4benzodiazepin-2-on, sleeping pill, tranquilizer, Valium
 
  
Substance type: benzodiazepine
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= History =
  
Diazepam, better known as Valium, was originally synthesized in the laboratory and introduced as a therapeutic drug (psychopharmaca, tranquilizer) in the 1960s. The substance produces sedative, euphoric, and especially anxiolytic (anxietyreducing) effects (Henningfield 1988, 17,35*). During the investigation of diazepam's pharmacology, it was discovered that the human nervous system has a special receptor for this molecule, known as the benzodiazepine receptor or the [3H] -diazepam receptor. Luk et al. (1983) found three isoflans in the urine of cattle that may possibly dock (as neurotransmitters) in the benzodiazepine receptor. It is known that the kavapyrones (cf. Piper methysticum) bind to the [3H] -diazepam receptor.  
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Diazepam was the second [[Benzodiazepines|benzodiazpine]] (The first of which was Librium) invented by Dr. Leo Sternbach of Hoffmann-La Roche at the company’s Nutley, New Jersey, facility. It was released in 1963 as an improved version of Librium, it became incredibly popular.
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Diazepam was the top-selling pharmaceutical in the United States from 1969 to 1982, with peak sales in 1978 of 2.3 billion tablets.
  
Recently, flavonoids in the buds of the South American linden tree (Tilia tomentosa Moench; Tiliaceae; cf. tila) were found to bind to the benzodiazepine receptor. A substance found in Passiflora caerulea 1. (cf. Passiflora spp.), 5,7-dihydroxyflavone, also docks to the same location (Viola et al. 1994). The benzodiazepine receptor has been shown to be present in all vertebrates, suggesting that it appeared at a very early date in the evolution of the nervous system and has been preserved into the present. This indicates that it plays an important function in the nervous system and that there are endogenous substances that bind to it in order to transmit certain messages (Muller 1988). But what do these substances look like? At first they were thought to be polypeptides, but then traces of diazepam and desmethyldiazepam were discovered in the brains of humans and other animals. Because diazepam and its initial metabolite appear in breast milk and the placenta after the ingestion of Valium (Wessen et al. 1985), it was first believed that the diazepam must have been introduced into the body from outside" But when diazepam was subsequently also found to be present in brains that dated to a time before the discovery of Valium synthesis, it was concluded that diazepam was not a synthetic chemical at all but a naturally occurring neurotransmitter in the nervous system (Muller 1988). Thus it was demonstrated that "Valium, the very symbol of chemical psychopharmaca" (Zehentauer 1992, 121 *), is actually a natural substance.  
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= Formulations =
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It is available in instant release formulations of 2mg, 5mg, and 10mg tablets.
  
Pharmacologists were surprised when subsequent research demonstrated the presence of diazepam and desmethyldiazepam in potatoes (Solanum tuberosum 1.; cf. Solanum spp.) and in such diverse grains as wheat (Triticum aestivum 1.; cf. beer), corn/maize (Zea mays), and rice (Oryza sativa 1.; cf. sake) (Muller 1988). Valium, in other words, is a natural active constituent in plants. However, the concentration in these plants is so low that a person would likely not notice any Valium effects even after consuming a whole sack of potatoes. Valium is one of the most widely used sedative drugs in modern society and is normally prescribed for the treatment of anxiety and sleeping disorders.498 Not surprisingly, Valium also finds use as a recreational drug in some circles, particularly in combination with other substances. Its euphoric properties can be greatly affected by alcohol, which can at times counteract the sedative properties, resulting in powerful stimulating effects. Valium is one of the more commonly used psychopharmaca in the music scene. Several rock bands, including the classic "space rock" band Hawkwind CValium 10," 1978), have dedicated titles to the substance.
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It is also available in an oral solution of 5mg/5ml (1mg/ml)
  
== Commercial Forms and Regulations ==
 
  
Valium is available by prescription only. In the United States, it is listed as a Schedule IV drug under the Controlled Substances Act.
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= Doses =
  
== Literature ==
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NOTE: Higher doses have an increased risk of blacking out.
  
Flesch, Peter. 1996. SchlafstOrungen bei iilteren Patienten: Auf Benzodiazepine kann meist verzichtet werden. Jatros Neurologie 12:6-7 (interview).
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{| class="wikitable"
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|+ Oral
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| Light || 2.5-5mg
  
Henningsfield, Jack E. 1988. Barbiturates: Sleeping potion or intoxicant. The Encyclopedia of
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|-
  
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| Common || 5-15mg
  
Psychoactive Drugs. London, Toronto, and New
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|-
York: Burke Publishing Company.
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Luk, Kin-Chun, Lorraine Stern, Manfred Weigele,
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|Heavy || 15-30mg+
  
Robert A. O'Brien, and Nena Sprit. 1983.
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|}
  
Isolation and identification of "diazepam-like"
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= Duration =
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Note: Duration can be significantly longer with higher doses.
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{| class="wikitable"
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|+ Oral
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|-
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| Onset || 30-90 Minutes
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|-
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| Total || Up to 24 hours, Main effects are generally felt for roughly 8-12 hours.
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|}
  
compounds from bovine urine. Journal of
 
  
Natural Products 46 (6): 852-61.
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= Effects =
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== Positive ==
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*Euphoria
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*Relaxation
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*Anti-Anxiety effects
  
Muller, Walter E. 1988. Sind Benzodiazipine 100%
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== Neutral ==
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*Drowsiness
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*Appetite fluctuation
  
Natur? Deutsche Apotheker Zeitung126 (13): 672-74.
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== Negative ==
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*Memory loss
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*Blackout potential
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*Motor skill impairment
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*Dizziness
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*Depression
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*Irritability, aggression, rage
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*Personality changes
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*Emotional and social dissociation or de-realization (long term use)
  
Viola, H., C. Wolfman, M. Levi de Stein, C.
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= Harm Reduction =
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When on high doses of [[Benzodiazepines|benzodiazepines]], users are likely to black out and potentially hurt themselves through a variety of adventures. If you are using it as a sleep aid, it's recommended to continue doing what you're doing until you begin to feel drowsy, then go to bed.
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Some users report Diazepam (and [[Benzodiazepines|benzodiazepines]] in general) to lead to compulsive redosing, trying to find a “high” which is where a fair amount of the point above comes from. To avoid this keep doses low and be wary of reduced inhibitions while under the influence of Diazepam.
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== Interactions ==
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As with other depressants, Diazepam should not be combined with any other CNS depressants (such as [[Alcohol]]), at the risk of respiratory depression, which can lead to death.
  
Wasowski, C. Pena, J. H. Medina, and A. C.
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See the [[Drug combinations]] chart for more information.
  
Paladini. 1994. Isolation of pharmacologically
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= Chemistry and Pharmacology =
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Diazepam can be administered orally, intravenously (Has to be diluted, as it is painful and damaging to veins), intramuscularly, or as a suppository.
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Peak plasma levels occur between 30 and 90 minutes after oral administration and between 30 and 60 minutes after intramuscular administration; 10-45 minutes for Rectal, and between 1-5 minutes intravenously.
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Diazepam is highly protein-bound, with 95-99% of the absorbed drug being protein-bound.
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Diazepam is highly lipid-soluble, and is widely distributed throughout the body after administration. It easily crosses the blood-brain-barrier. After absorption, diazepam is redistributed into muscle and adipose tissue. Continual dialy doses of Diazepam quickly build to a high concentration in the body (mainly in adipose tissue)
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Diazepam unergoes oxifative metabolism by demethylation (CYP 2C9, 2C19, 2B6, 3A4, and 3A5) hydroxylation (CYP 3A4 and 2C19) and glucuronidation in the liver as part of the cytochrome P450 enzyme system.
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The main active metabolite of diazepam is Desmethyldiazepam (Nordiazepam) Other metabolites inclue minor active metolites temazepam and oxazepam. 
  
active benzodiazepine receptor ligands from Tilia
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= Legal Status =
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== International ==
  
tomentosa (Tiliaceae). Journal of
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Diazepam is a schedule IV controlled drug under the Convention on Psychotropic Substances.
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== UK ==
  
Psychopharmacology 44:47-53.
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Classified as a Class C drug.
  
Wesson, Donald R, Susan Camber, Martha Harkey,
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[[Category:Chemicals]]
  
and David E. Smith. 1985. Diazepam and
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[[Category:Drugs]]
  
desmethyldiazepam in breast milk. Journal of
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[[Category:Depressant]]
 
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Psychoactive Drugs 17 (1): 55-56.
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Latest revision as of 10:36, 26 June 2015

Diazepam (Also known as Diastat; Valium; Zetran) is a benzodiazepine that is commonly used to treat a large range of conditions from anxiety to Meniere’s Disease. It possesses anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnesic properties. It is also one of the most commonly used drugs to taper off of other benzodiazepines/Alcohol withdrawal.


History

Diazepam was the second benzodiazpine (The first of which was Librium) invented by Dr. Leo Sternbach of Hoffmann-La Roche at the company’s Nutley, New Jersey, facility. It was released in 1963 as an improved version of Librium, it became incredibly popular. Diazepam was the top-selling pharmaceutical in the United States from 1969 to 1982, with peak sales in 1978 of 2.3 billion tablets.

Formulations

It is available in instant release formulations of 2mg, 5mg, and 10mg tablets.

It is also available in an oral solution of 5mg/5ml (1mg/ml)


Doses

NOTE: Higher doses have an increased risk of blacking out.

Oral
Light 2.5-5mg
Common 5-15mg
Heavy 15-30mg+

Duration

Note: Duration can be significantly longer with higher doses.

Oral
Onset 30-90 Minutes
Total Up to 24 hours, Main effects are generally felt for roughly 8-12 hours.


Effects

Positive

  • Euphoria
  • Relaxation
  • Anti-Anxiety effects

Neutral

  • Drowsiness
  • Appetite fluctuation

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)

Harm Reduction

When on high doses of benzodiazepines, users are likely to black out and potentially hurt themselves through a variety of adventures. If you are using it as a sleep aid, it's recommended to continue doing what you're doing until you begin to feel drowsy, then go to bed. Some users report Diazepam (and benzodiazepines in general) to lead to compulsive redosing, trying to find a “high” which is where a fair amount of the point above comes from. To avoid this keep doses low and be wary of reduced inhibitions while under the influence of Diazepam.

Interactions

As with other depressants, Diazepam should not be combined with any other CNSCentral Nervous System depressants (such as Alcohol), at the risk of respiratory depression, which can lead to death.

See the Drug combinations chart for more information.

Chemistry and Pharmacology

Diazepam can be administered orallyRoute of administration in which the subject swallows a substance., intravenously (Has to be diluted, as it is painful and damaging to veins), intramuscularly, or as a suppository. Peak plasma levels occur between 30 and 90 minutes after oral administrationRoute of administration in which the subject swallows a substance. and between 30 and 60 minutes after intramuscular administration; 10-45 minutes for Rectal, and between 1-5 minutes intravenously. Diazepam is highly protein-bound, with 95-99% of the absorbed drug being protein-bound. Diazepam is highly lipid-soluble, and is widely distributed throughout the body after administration. It easily crosses the blood-brain-barrier. After absorption, diazepam is redistributed into muscle and adipose tissue. Continual dialy doses of Diazepam quickly build to a high concentration in the body (mainly in adipose tissue) Diazepam unergoes oxifative metabolism by demethylation (CYP 2C9, 2C19, 2B6, 3A4, and 3A5) hydroxylation (CYP 3A4 and 2C19) and glucuronidation in the liver as part of the cytochrome P450 enzyme system. The main active metabolite of diazepam is Desmethyldiazepam (Nordiazepam) Other metabolites inclue minor active metolites temazepam and oxazepam.

Legal Status

International

Diazepam is a schedule IV controlled drug under the Convention on Psychotropic Substances.

UK

Classified as a Class C drug.

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