Originally marketed as Valium, it is a drug in the benzodiazepine family that generally produces a calming effect.
It is commonly used to treat a variety of conditions including anxiety, withdrawal symptoms of alcohol withdrawal syndrome benzodiazepines, muscle spasms, convulsions, sleep problems and restless leg syndrome.
It can also be used to cause memory loss during certain medical procedures. It can be taken by mouth, inserted into the rectum, injected into the muscle, or injected into a vein.
When given into a vein, the effects start in one to five minutes and last up to an hour. Taken orally, the effects may take 40 minutes to begin.
Common side effects include drowsiness and problems with coordination. Serious side effects are rare. They include suicide, decreased breathing, and an increased risk of seizures if used too often in people with epilepsy.
Occasionally there may be excitement or agitation. Long-term use can lead to tolerance, dependence and withdrawal symptoms on dose reduction. An abrupt discontinuation after long-term use can be potentially dangerous.
After stopping use, cognitive problems can persist for six months or more. It is not recommended during pregnancy or lactation. Its mechanism of action is to increase the effect of the neurotransmitter gamma-aminobutyric acid (GABA).
Diazepam was manufactured by Leo Sternbach and marketed by Hoffmann-La Roche. In the United States it was the best-selling drug between 1968 and 1982, selling more than two billion tablets in 1978 alone.
In 1985, the patent ended and there are now more than 500 brands available on the market. Diazepam is on the World Health Organization’s Essential Medicines List, the safest and most effective medicines needed in a health system.
The wholesale cost in the developing world is approximately $ 0.01 per dose as of 2014. In the United States it is approximately $ 0.40 per dose.
Diazepam is used primarily to treat anxiety, insomnia, panic attacks, and acute alcohol withdrawal symptoms. It is also used as a premedication to induce sedation, anxiolysis, or amnesia before certain medical procedures (eg, endoscopy).
Diazepam has a number of uses including:
- Treatment of anxiety, panic attacks and states of agitation.
- Treatment of neurovegetative symptoms associated with vertigo.
- Treatment of alcohol, opiate, and benzodiazepine withdrawal symptoms.
- Short-term treatment of insomnia.
- Treatment of tetanus, along with other intensive treatment measures.
- Adjuvant treatment of spastic muscular paresis (paraplegia / tetraplegia) caused by brain or spinal cord conditions, such as stroke, multiple sclerosis, or spinal cord injury (long-term treatment is combined with other rehabilitation measures).
- Palliative treatment of stiff person syndrome. Pre or postoperative sedation, anxiolysis, or amnesia (such as before endoscopic or surgical procedures).
- Treatment of complications with a hallucinogen crisis and stimulant overdose and psychoses, such as lysergic acid diethylamide (LSD), cocaine, or methamphetamine.
- Preventive treatment of oxygen toxicity during hyperbaric oxygen therapy.
Doses should be determined on an individual basis, based on the condition being treated, the severity of the symptoms, the patient’s body weight, and any other conditions the person may have.
Intravenous diazepam or lorazepam are first-line treatments for status epilepticus. However, intravenous lorazepam has advantages over intravenous diazepam, including a higher rate of terminal seizures and a longer anti-seizure effect.
Diazepam gel was better than placebo gel in reducing the risk of non-cessation of seizures. Diazepam is rarely used for the long-term treatment of epilepsy because tolerance to its anticonvulsant effects generally develops within six to 12 months of treatment, rendering it useless for that purpose.
The anticonvulsant effects of diazepam may aid in the treatment of seizures due to drug overdose or chemical toxicity resulting from exposure to sarin, poisonous agent X (VX) or soman (or other organophosphate poisons), lindane, chloroquine, physostigmine, or pyrethroids.
Diazepam is sometimes used intermittently to prevent febrile seizures that can occur in children under five years of age. Recurrence rates are reduced, but side effects are common.
Long-term use of diazepam is not recommended for the treatment of epilepsy; however, a subset of individuals with refractory epilepsy benefit from benzodiazepines in the long term, and for such individuals, chlorazepate has been recommended because of its slower-onset tolerance to anticonvulsant effects.
Diazepam is used for the emergency treatment of eclampsia, when intravenous (IV) therapy, magnesium sulfate, and blood pressure control measures have failed.
Benzodiazepines do not have analgesic properties, and they are generally recommended to be avoided in people with pain.
However, benzodiazepines such as diazepam can be used for their muscle relaxant properties to relieve pain caused by muscle spasms and various dystonia, including blepharospasm.
Tolerance to the muscle relaxant effects of benzodiazepines, such as diazepam, often develops. Baclofen or tizanidine is sometimes used as an alternative to diazepam.
Diazepam is marketed under more than 500 brands around the world. It is supplied in oral, injectable, inhalation, and rectal forms.
The United States military uses a specialized preparation of diazepam known as Convulsive Antidote, Nervous Agent (CANA), which contains diazepam.
A seizure antidote nerve agent kit is generally issued to service members, along with three Mark I Antidote Kit (NAAK) kits when used in circumstances where chemical weapons in form of nerve agents are considered a potential hazard.
Both kits deliver drugs using autoinjectors. They are intended for use in the “buddy help” or “self-help” administration of drugs in the field prior to decontamination and delivery of the patient for definitive medical care.
The use of diazepam should be avoided, when possible, in people with:
- Severe hypoventilation.
- Acute narrow-angle glaucoma.
- Severe liver deficiencies (hepatitis and liver cirrhosis decrease elimination by a factor of two).
- Severe kidney deficiencies (for example, dialysis patients).
- Liver disorders
- Severe sleep apnea
- Severe depression, particularly when accompanied by suicidal tendencies.
- Pregnancy or breastfeeding
- Caution is required in elderly or debilitated patients.
- Eat the shock. Abrupt discontinuation of therapy.
- Acute intoxication with alcohol, narcotics or other psychoactive substances (with the exception of some hallucinogens or stimulants, where it is occasionally used as a treatment for an overdose).
- History of alcohol or drug dependence. Myasthenia gravis, an autoimmune disorder that causes marked fatigue. Hypersensitivity or allergy to any drug in the benzodiazepine class.
The misuse of benzodiazepines should be avoided when prescribed to people with alcohol or drug dependence or who have psychiatric disorders.
This treatment is generally not indicated for patients under 18 years of age, except for the treatment of epilepsy and preoperative or postoperative treatment. The smallest possible effective dose should be used for this group of patients.
Under 6 months of age, safety and effectiveness have not been established; Diazepam should not be given to those in this age group.
Very sick and elderly patients may suffer apnea or cardiac arrest. The smallest possible effective dose should be used for this group of people.
Diazepam doses are recommended to be about half of those given to younger people, and treatment is limited to a maximum of two weeks.
Diazepam can also be dangerous in geriatric patients due to a significantly increased risk of falls.
Intravenous or intramuscular injections in hypotensive or shocked persons should be administered with care and vital signs should be monitored.
Diazepam when taken late in pregnancy, during the third trimester, causes a definite risk of severe benzodiazepine withdrawal syndrome in the neonate with symptoms including hypotonia and reluctance to suck, episodes of apnea, cyanosis, and altered metabolic responses to stress by cold.
Hypotonia and sedation in the newborn can also occur. Symptoms of hypotonia and neonatal benzodiazepine withdrawal syndrome have been reported to persist for hours to months after birth.
Effects include anterograde amnesia and confusion (especially pronounced at higher doses) and sedation. The elderly are more prone to the adverse effects of diazepam, such as confusion, amnesia, ataxia, and the effects of a hangover, as well as falls.
Long-term use of benzodiazepines such as diazepam is associated with drug tolerance, benzodiazepine dependence, and benzodiazepine withdrawal syndrome.
Like other benzodiazepines, diazepam can affect short-term memory and the learning of new information.
While benzodiazepine drugs such as diazepam can cause anterograde amnesia, they do not cause retrograde amnesia; information learned before using benzodiazepines is not affected.
Tolerance to the cognitive impairment effects of benzodiazepines does not tend to develop with long-term use, and the elderly are more sensitive to them.
Repeated infusions or intravenous injections of diazepam when managing seizures, for example, can lead to drug toxicity, including respiratory depression, sedation, and hypotension.
Tolerance to the drug can also develop diazepam infusions if given for more than 24 hours. Adverse effects such as sedation, dependence on benzodiazepines, and the potential for abuse limit the use of benzodiazepines.
Diazepam has a variety of side effects common to most benzodiazepines, including:
REM sleep suppression and slow wave sleep. Impaired motor function. Impaired coordination. Impaired balance. Dizziness. Depression. Reflex tachycardia.
Less frequently, paradoxical side effects may appear, such as nervousness, irritability, excitement, worsening of seizures, insomnia, muscle cramps, changes in libido and, in some cases, anger and violence.
These adverse reactions are more likely to occur in children, the elderly, and individuals with a history of alcohol or drug abuse and / or assault.
Diazepam can increase the propensity for self-destructive behaviors in some people and, in extreme cases, can cause suicidal tendencies or acts. Very rarely dystonia can occur.
Diazepam can affect the ability to drive vehicles or operate machinery. The deterioration is worsened with alcohol consumption, since both act as central nervous system depressants.
During the course of therapy, tolerance generally develops to the sedative effects, but not to the anxiolytic and muscle relaxant effects.
Diazepam in doses of 5 mg or more causes a significant deterioration in the performance of alertness combined with an increased feeling of drowsiness.
Tolerance and dependency
Diazepam, like other benzodiazepine medications, can cause tolerance, physical dependence, substance use disorder, and benzodiazepine withdrawal syndrome.
Withdrawal from diazepam or other benzodiazepines often leads to withdrawal symptoms similar to those seen during withdrawal from barbiturates or alcohol.
The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms.
Withdrawal symptoms can occur from standard doses and also after short-term use, and can range from insomnia and anxiety to more severe symptoms such as seizures and psychosis.
Withdrawal symptoms can sometimes resemble pre-existing conditions and can be misdiagnosed. Diazepam may cause less severe withdrawal symptoms due to its long elimination half-life.
Tolerance develops to the therapeutic effects of benzodiazepines; for example, tolerance to anticonvulsant effects occurs, and as a result, benzodiazepines are generally not recommended for the long-term treatment of epilepsy.
Increasing the dose may overcome the effects of tolerance, but tolerance may develop at the higher dose and adverse effects may increase.
The mechanism of tolerance to benzodiazepines includes uncoupling of receptor sites, alterations in gene expression, down-regulation of receptor sites, and desensitization of receptor sites to the effect of gamma-aminobutyric acid.
About a third of people who take benzodiazepines for more than four weeks become dependent and experience withdrawal syndrome upon cessation.
Differences in abstinence rates (50-100%) vary by patient sample.
For example, a random sample of long-term benzodiazepine users generally finds that about 50% experience little or no withdrawal symptoms, while the other 50% experience noticeable withdrawal symptoms.
Certain selected patient groups show a higher rate of notable withdrawal symptoms, up to 100%.
Rebound anxiety, more severe than initial anxiety, is also a common withdrawal symptom when stopping use of diazepam or other benzodiazepines.
Therefore, diazepam is only recommended for short-term treatment with the lowest possible dose due to the risks of serious withdrawal problems from low doses, even after a gradual reduction.
The risk of drug dependence on diazepam is significant, and patients experience symptoms of benzodiazepine withdrawal symptoms if taken for six weeks or longer. In humans, tolerance to the anticonvulsant effects of diazepam occurs frequently.
Incorrect or excessive use of diazepam can lead to dependence. At particularly high risk for diazepam misuse, abuse, or dependence are:
People with a history of alcohol or drug abuse or dependence, since Diazepam increases the desire to consume, in people with alcohol problems.
People with severe personality disorders, such as borderline personality disorder.
Patients in the aforementioned groups should be closely monitored during therapy for signs of abuse and development of dependence.
Therapy should be discontinued if any of these signs are observed, although if dependence has developed, therapy should be discontinued gradually to avoid severe withdrawal symptoms. Long-term therapy in such cases is not recommended.
People suspected of being dependent on benzodiazepine medications should gradually reduce the medication.
Withdrawals can be life-threatening, especially when excessive doses have been taken for long periods of time. The same caution should be used regardless of whether the dependence has occurred in therapeutic or recreational settings.
A person who has taken too much diazepam usually shows one or more of these symptoms in about four hours immediately after a possible overdose:
- Mental confusion.
- Impaired motor functions.
- Impaired reflexes.
- Impaired coordination.
- Impaired balance.
The oral LD50 (lethal dose in 50% of the population) of diazepam is 720 mg / kg in mice and 1240 mg / kg in rats.
DJ Greenblatt and colleagues reported in 1978 that two patients who had taken 500 and 2000 mg of diazepam, respectively, entered a moderately deep coma, and were discharged within 48 hours without experiencing major complications.
Despite having high concentrations of diazepam and its metabolites desmethyldiazepam, oxazepam and temazepam, according to samples taken in the hospital and as a follow-up.
Diazepam overdoses with alcohol, opiates, or other depressants can be fatal.
If diazepam is administered concomitantly with other medicinal products, attention should be paid to possible drug interactions. Special care should be taken with medications that potentiate the effects of diazepam, such as barbiturates, phenothiazines, opioids, and antidepressants.
Diazepam does not increase or decrease the activity of liver enzymes, and it does not alter the metabolism of other compounds. No evidence would suggest that diazepam alters its own metabolism with chronic administration.
Agents with an effect on hepatic cytochrome P4 pathways or conjugation may alter the rate of metabolism of diazepam. These interactions are expected to be more significant with long-term diazepam treatment, and their clinical significance is variable.
Diazepam increases the central depressant effects of alcohol, other hypnotics / sedatives (eg, barbiturates), other muscle relaxants, certain antidepressants, sedative antihistamines, opioids, and antipsychotics, as well as anticonvulsants such as phenobarbital, phenytoin, and carbamazepine.
The euphoric effects of opioids can be increased, increasing the risk of psychological dependence.
Cimetidine, omeprazole, oxcarbazepine, ticlopidine, topiramate, ketoconazole, itraconazole, disulfiram, fluvoxamine, isoniazid, erythromycin, probenecid, propranolol, imipramine, ciprofloxacin, fluoxetine and valproic acid prolong their elimination by inhibiting their elimination.
Oral contraceptives significantly decrease the elimination of desmethyldiazepam, a major metabolite of diazepam.
Rifampin, phenytoin, carbamazepine, and phenobarbital increase the metabolism of diazepam, thus decreasing the levels and effects of the drug. Dexamethasone and St. John’s wort also increase the metabolism of diazepam.
Diazepam increases serum phenobarbital levels. Nefazodone can cause elevated levels of benzodiazepines in the blood. Cisapride can improve the absorption, and therefore the sedative activity, of diazepam.
Small doses of theophylline can inhibit the action of diazepam. Diazepam can block the action of levodopa (used to treat Parkinson’s disease). Diazepam can alter serum digoxin concentrations.
Other drugs that can interact with diazepam include antipsychotics (eg, chlorpromazine), monoamine oxidase (MAO) inhibitors, and ranitidine.
Because it acts on the gamma-aminobutyric acid receptor, valerian herbs can have an adverse effect.
Foods that acidify the urine can lead to faster absorption and elimination of diazepam, reducing drug levels and activity.
Foods that alkalize the urine can lead to slower absorption and elimination of diazepam, increasing drug levels and activity.
Reports do not agree on whether food in general has an effect on the absorption and activity of orally administered diazepam.
Diazepam is a long-acting “classic” benzodiazepine. Other classic benzodiazepines include chlordiazepoxide, clonazepam, lorazepam, oxazepam, nitrazepam, temazepam, flurazepam, bromazepam, and clorazepate. Diazepam has anticonvulsant properties.
Diazepam has no effect on gamma-aminobutyric acid levels and has no effect on glutamate decarboxylase activity, but has a slight effect on gamma-aminobutyric acid transaminase activity.
It differs from some of the other anti-seizure medications that it was compared to.
Benzodiazepines act through micromolar benzodiazepine binding sites as calcium channel blockers and significantly inhibit depolarization-sensitive calcium uptake in rat nerve cell preparations.
Diazepam inhibits acetylcholine release from hippocampal synaptosomes in mice. This has been found by measuring sodium-dependent high-affinity choline uptake in mouse brain cells in vitro, after pre-treatment of mice with diazepam in vivo.
This may play a role in explaining the anticonvulsant properties of diazepam. Diazepam binds glial cells with high affinity in animal cell cultures.
High-dose diazepam has been found to decrease histamine turnover in mouse brain through the action of diazepam on the benzodiazepine-gamma-Aminobutyric acid receptor complex. Diazepam also decreases prolactin release in rats.
Mechanism of action
Benzodiazepines are positive allosteric modulators of gamma-aminobutyric acid (GABAA) type A receptors.
Gamma-aminobutyric acid type A receptors are ligand-gated chloride-selective ion channels that are activated by gamma-aminobutyric acid, the major inhibitory neurotransmitter in the brain.
The binding of benzodiazepines to this receptor complex promotes the binding of gamma-aminobutyric acid, which in turn increases the total conduction of chloride ions across the neuronal cell membrane.
This increased influx of chloride ions hyperpolarizes the membrane potential of the neuron.
As a result, the difference between the resting potential and the action potential increases and the operation is less likely. As a result, the activation of the cortical and limbic systems in the central nervous system is reduced.
The gamma-aminobutyric acid receptor type A is a heteromer composed of five subunits, the most common being two αs, two βs and one γ (α2β2γ). For each subunit, there are many subtypes (α1-6, β1-3, and γ1-3).
Type A receptors for gamma-aminobutyric acid containing the α1 subunit mediate the sedative, anterograde amnesic, and, in part, the anticonvulsant effect of diazepam.
The a2-containing gamma-aminobutyric acid type A receptors mediate anxiolytic actions and to a large extent muscle relaxant effects.
Gamma-aminobutyric acid type A receptors containing α3 and α5 also contribute to the muscle relaxant actions of benzodiazepines, while gamma-aminobutyric acid type A receptors containing the α5 subunit modulate the effects of temporary memory and of benzodiazepines.
Diazepam is not the only drug that targets these type A gamma-aminobutyric acid receptors. Medications such as flumazenil also bind to gamma-aminobutyric acid type A to induce its effects.
Diazepam appears to act in areas of the limbic system, the thalamus, and the hypothalamus, inducing anxiolytic effects. Benzodiazepine drugs, including diazepam, increase inhibitory processes in the cerebral cortex.
The anticonvulsant properties of diazepam and other benzodiazepines may be, in part or in whole, due to binding to voltage-gated sodium channels rather than to benzodiazepine receptors.
Sustained repetitive firing appears to be limited by the effect of benzodiazepines in slowing the recovery of sodium channels from inactivation.
The muscle relaxant properties of diazepam are produced by inhibiting polysynaptic pathways in the spinal cord.
Diazepam can be administered orally, intravenously (it must be diluted as it is painful and damaging to the veins), intramuscularly (IM), or as a suppository.
When administered orally, it is rapidly absorbed and has a rapid onset of action. Onset of action is one to five minutes for intravenous therapy administration and 15 to 30 minutes for intramuscular administration.
The duration of the maximum pharmacological effects of diazepam is 15 minutes to one hour for both routes of administration.
The bioavailability after oral administration is 100% and 90% after rectal administration. The half-life of diazepam in general is 30-56 hours.
Peak plasma levels occur between 30 and 90 minutes after oral administration and between 30 and 60 minutes after intramuscular administration; After rectal administration, peak plasma levels occur after 10 to 45 minutes.
Diazepam is highly protein bound, with 96 to 99% of the absorbed drug bound to proteins. The distribution half-life of diazepam is 2 to 13 minutes.
When diazepam is administered intramuscularly, absorption is slow, erratic, and incomplete.
Diazepam is highly lipid soluble and is widely distributed throughout the body after administration. It easily crosses both the blood-brain barrier and the placenta, and is excreted in breast milk.
After absorption, diazepam is redistributed in the muscles and adipose tissue.
Continuous daily doses of diazepam rise rapidly to a high concentration in the body (mainly adipose tissue), well above the actual dose for a given day.
Diazepam is preferentially stored in some organs, including the heart. Absorption by any administered route and the risk of accumulation are significantly increased in the newborn, and extraction of diazepam during pregnancy and lactation is clinically justified.
Diazepam undergoes oxidative 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. It has several pharmacologically active metabolites.
The main active metabolite of diazepam is desmethyldiazepam (also known as nordazepam or nordiazepam).
Its other active metabolites include the minor active metabolites temazepam and oxazepam. These metabolites are conjugated with glucuronide and are excreted mainly in the urine.
Due to these active metabolites, serum diazepam values alone are not useful in predicting drug effects.
Diazepam has a biphasic half-life of approximately one to three days, and two to seven days for the active metabolite desmethyldiazepam. Most of the drug is metabolized; very little diazepam is excreted unchanged.
The elimination half-life of diazepam and also the active metabolite desmethyldiazepam is significantly increased in the elderly, which can result in prolonged action, as well as accumulation of the drug during repeated administration.
Physical and chemical properties
Diazepam is a 1,4-benzodiazepine. Diazepam occurs as solid white or yellow crystals with a melting point of 131.5 to 134.5 ° C. It is odorless and has a slightly bitter taste.
The British Pharmacopoeia lists it as very slightly soluble in water, soluble in alcohol and freely soluble in chloroform. The United States Pharmacopeia lists diazepam as soluble in 1 in 16 ethyl alcohol, 1 in 2 in chloroform, 1 in ether 39, and practically insoluble in water.
The pH of diazepam is neutral (ie, pH = 7). Due to additives such as benzoic acid / benzoate in injectable form. (Plumb’s, 6th edition, page 372) Diazepam has a shelf life of five years for oral tablets and three years for intravenous / intramuscular therapy solutions.
Diazepam should be stored at room temperature (15-30 ° C). The solution for parenteral injection must be protected from light and freezing avoided. Oral forms should be stored in airtight containers protected from light.
Diazepam can be absorbed into plastics, so liquid preparations should not be stored in plastic bottles or syringes, etc. As such, it can leak into the plastic bags and tubes used for IV infusions.
Absorption appears to depend on several factors, such as temperature, concentration, flow rates, and tube length. Diazepam should not be administered if a precipitate has formed and does not dissolve.
Detection in body fluids
Diazepam can be quantified in blood or plasma to confirm a diagnosis of poisoning in hospitalized patients, provide evidence in an arrest for impaired driving, or assist in a medicolegal death investigation.
Diazepam concentrations in blood or plasma are generally in a range of 0.1-1.0 mg / l in people receiving the drug therapeutically, 1-5 mg / l in those arrested for impaired conduction, and 2-20 mg / l in victims of acute overdose.
Most commercial immunoassays for the benzodiazepine class of drugs cross-react with diazepam, but confirmation and quantification are generally performed using chromatographic techniques.
Diazepam was the second benzodiazepine invented by Leo Sternbach of Hoffmann-La Roche at the company’s facility in Nutley, NJ, after chlordiazepoxide (Librium), which was approved for use in 1960.
Launched in 1963 as an improved version of Librium, diazepam became incredibly popular, helping Roche become a giant in the pharmaceutical industry.
It is 2.5 times more powerful than its predecessor, which it quickly surpassed in terms of sales. After this initial success, other pharmaceutical companies began to introduce other benzodiazepine derivatives.
Benzodiazepines gained popularity among medical professionals as an improvement over barbiturates, which have a comparatively narrow therapeutic index, and are much more sedating at therapeutic doses.
Benzodiazepines are also much less dangerous; death is rarely the result of a diazepam overdose, except in cases where it is taken with large amounts of other depressants (such as alcohol or opiates).
Benzodiazepine drugs, such as diazepam, initially had broad public support, but over time the view shifted to growing criticism and demands restrictions on their prescription.
Marketed by Roche using an advertising campaign conceived by the William Douglas McAdams Agency under the leadership of Arthur Sackler, diazepam was the top-selling pharmaceutical in the United States from 1969 to 1982, with peak annual sales in 1978 of 2.3 billion tablets.
Diazepam, along with oxazepam, nitrazepam and temazepam, accounts for 82% of the benzodiazepine market in Australia.
While psychiatrists continue to prescribe diazepam for the short-term relief of anxiety, neurology has taken the lead in prescribing diazepam for the palliative treatment of certain types of epilepsy and spastic activity, eg forms of paresis.
It is also the first line of defense for a rare disorder called stiff person syndrome.
Society and culture
Diazepam is a drug of possible abuse and can cause drug dependence. Urgent action by national governments has been recommended to improve prescribing patterns for benzodiazepines, such as diazepam.
A single dose of diazepam modulates the dopamine system in a similar way to how morphine and alcohol modulate dopamine pathways. Between 50 and 64% of rats will self-administer diazepam.
Diazepam has been shown to substitute for the behavioral effects of barbiturates in a primate study. Diazepam has been found as an adulterant in heroin.
Diazepam misuse can occur either through recreational misuse when the drug is taken to reach a high level or when the drug is continued long-term against medical advice.
Stimulant users sometimes use it to “calm down” and sleep, and to help control the urge to binge. These users often increase the dose 2 to 25 times the therapeutic dose of 5 to 10 mg.
A large-scale study in the US, conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA), using data from 2011.
It determined that benzodiazepines were present in 28.7% of emergency department visits that involved the non-medical use of pharmaceuticals.
In this sense, benzodiazepines are second only to opiates, the study found in 39.2% of visits.
Approximately 29.3% of drug-related suicide attempts involve benzodiazepines, making them the most frequently represented class of drug-related suicide attempts.
Men abuse benzodiazepines as commonly as women.
Benzodiazepines, which include diazepam, nitrazepam, and flunitrazepam, account for the largest volume of counterfeit drug prescriptions in Sweden; a total of 52% of counterfeit drugs refer to benzodiazepines.
Diazepam was detected in 26% of cases of people suspected of driving under the influence in Sweden, and its active metabolite nordazepam was detected in 28% of cases.
Other benzodiazepines and zolpidem and zopiclone were also found in large quantities.
Many drivers had blood levels that far exceeded the therapeutic dose range, suggesting a high degree of abuse potential for benzodiazepines and zolpidem and zopiclone.
In Northern Ireland, where drugs were detected in samples of disabled drivers who did not have alcohol problems, benzodiazepines were found in 87% of cases. Diazepam was the most commonly detected benzodiazepine.
Diazepam is regulated in most countries as a prescription drug:
International : Diazepam is a Schedule IV controlled drug under the Convention on Psychotropic Substances.
United Kingdom : classified as a controlled drug, included in Schedule IV, Part I (CD Benz POM) of the Drug Abuse Regulations 2001, which allows possession with a valid prescription.
The Drug Abuse Act of 1971 makes it illegal to possess the drug without a prescription, and for such purposes it is classified as a Class C drug.
Germany : classified as a prescription drug, or in high doses as a restricted drug (Betäubungsmittelgesetz, Anlage III).
Australia : Diazepam is a Schedule 4 substance according to the Poisons Standard (October 2015). A Schedule 4 drug is described in the Poisons Act of 1964 as:
“Substances whose use or supply must be according to or by order of persons permitted by state or territorial legislation to prescribe and must be available from a pharmacist with a prescription.”
USA : Diazepam is controlled as a Schedule IV substance under the Controlled Substances Act of 1970.
The states of California and Florida offer diazepam to convicted prisoners as a pre-execution sedative as part of their lethal injection program, although the state of California has not executed a prisoner since 2006.
Diazepam is used as a short-term sedative and anxiolytic for cats and dogs, sometimes used as an appetite stimulant. It can also be used to stop seizures in dogs and cats.