Diazepam

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.

Diazepam
The skeletal formula of diazepam
Chemical Nomenclature
Common names	Diazepam, Valium, Diastat, Mothers little helper
Systematic name	7-Chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one
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 5 mg - 10 mg Light 10 - 20 mg Common 20 - 30 mg Strong 40 - 50 mg Heavy 50 mg + Duration Total 4 - 6 hours Onset 15 - 90 minutes

Summary sheet: Diazepam

Diazepam, first marketed as Valium by Hoffmann-La Roche, is a benzodiazepine drug. It is commonly used to treat a wide range of conditions including anxiety, panic attacks, insomnia, seizures, muscle spasms, restless legs syndrome, alcohol withdrawal syndrome, benzodiazepine withdrawal syndrome, opiate withdrawal syndrome, and Ménière's disease.

It may also be used before certain medical procedures (such as endoscopies) to reduce tension and anxiety and in some surgical procedures to induce amnesia. As an alternative, it may be used to hasten the onset of intravenous (IV) anaesthesia while reducing dose requirements or as the sole agent when IV anaesthesia is not available or is contraindicated. It possesses anxiolytic, anticonvulsant, sedative, muscle relaxant, and amnestic properties.

The pharmacological action of diazepam enhances the effect of the neurotransmitter GABA by binding to the benzodiazepine site on the GABAA receptor (via the constituent chlorine atom) leading to central nervous system depression. Advantages of diazepam are a rapid onset of action and high efficacy rates, which are important for managing acute seizures and panic attacks. Benzodiazepines also have a relatively low toxicity in overdose.

Diazepam is a core medicine in the World Health Organization's Essential Drugs List, the minimum medical needs for a basic health-care system. Diazepam, first synthesized by Leo Sternbach, has been one of the most frequently prescribed medications in the world since its launch in 1963.

Chemistry

Diazepam 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. At R₁, diazepam is substituted with methyl group. Further, the benzodiazepine ring is bonded at R₅ to an aromatic phenyl ring. The benzyl ring of the bicyclic core is substituted at R₇ with a chlorine group. Diazepam also contains an oxygen group double bonded to R₂ of its diazepine ring to form a ketone. This oxygen substitution at R₂ is shared with other benzodiazepine drugs with the suffix -azepam.

Pharmacology

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 within the brain, its modulation results in the sedating (or calming effects) of diazepam on the nervous system.

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 diazepam can be broken down into several components which progressively intensify proportional to dosage.

The most prominent of these cognitive effects generally include:

• Muscle relaxation - In comparison to alprazolam (Xanax), diazepam has greater amounts of muscle relaxation.
• Sedation - In terms of energy level alterations, this drug is 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.
• Motor control loss
• Respiratory depression
• Dizziness
• Seizure suppression

Cognitive effects

The cognitive effects of diazepam can be broken down into several components which progressively intensify proportional to dosage. The general head space of diazepam 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:

• Anxiety suppression
• Disinhibition
• Thought deceleration
• Amnesia
• 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

Lethal dosage

The oral LD50 (lethal dose in 50% of the population) of diazepam is 720 mg/kg in mice and 1240 mg/kg in rats. D. J. Greenblatt and colleagues reported in 1978 on two patients who had taken 500 and 2000 mg of diazepam, went into moderately deep comas, and were discharged within 48 hours without having experienced any important complications in spite of having high concentrations of diazepam and its metabolites esmethyldiazepam, oxazepam, and temazepam (according to samples taken in the hospital and as follow-up).

Although not usually fatal when taken alone, a diazepam overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. The antidote for an overdose of diazepam (or any other benzodiazepine) is flumazenil (Anexate). This drug is only used in cases with severe respiratory depression or cardiovascular complications. Because flumazenil is a short-acting drug and the effects of diazepam can last for days, several doses of flumazenil may be necessary. Artificial respiration and stabilization of cardiovascular functions may also be necessary.

Overdoses of diazepam with alcohol, opiates and/or other depressants can be fatal.

Tolerance and addiction potential

Tolerance will develop to the sedative-hypnotic effects within a couple of 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 seizures following discontinuation of benzodiazepines. Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.

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

Diazepam is regulated in most countries as a prescription drug.

• International: Diazepam is a Schedule IV controlled drug under the Convention on Psychotropic Substances.
• UK: The drug is classified as a controlled drug and listed under Schedule IV, Part I (CD Benz POM) of the Misuse of Drugs Regulations 2001, allowing possession with a valid prescription. The Misuse of Drugs Act 1971 makes it illegal to possess the drug without a prescription and, for such purposes, it is classified as a Class C drug.
• Germany: Diazepam is classified as a prescription drug, or in high dosage, as a restricted drug (Betäubungsmittelgesetz, Anhang III).

Preparation methods

Preparation methods for this compound within our preparation index include:

• Volumetric liquid dosing

See also

• Responsible use
• Psychoactive substance index
• Diclazepam
• Benzodiazepines
• Depressants